Infliximab and the Risk of Tuberculosis — Case Reports and Other Postmarketing Data
A search of the published literature for infliximab revealed 65 postmarketing case reports where tuberculosis (TB) was diagnosed and temporally associated with a patient receiving infliximab. These cases, including outcome data where available, are presented in the following table. There were 6 patients with ankylosing spondylitis (AS), 8 with Crohn’s disease (CD), 4 with psoriatic arthritis (PsA), 5 with psoriasis (PsO), 35 with rheumatoid arthritis (RA), and 7 patients with other diseases. A history of previous immunosuppressant use and/or concomitant medication use was reported in the majority of patients. Sixteen patients had negative tuberculin skin test (TST) and/or chest x-ray (CXR) exams prior to the start of infliximab treatment (in two of these patients, one of whom had been in close contact with an individual with smear-positive, pulmonary TB, the tests were not specified, but both patients screened negative for TB prior to infliximab therapy). One patient who tested negative for TB during screening had possible TB exposure as a child. Another patient had a history of pulmonary TB at 8 years of age and spent a year in a sanatorium, but did not receive appropriate antibiotic treatment at that time. A third patient was TST positive 10 years prior to admission, but TST negative 4 years prior to admission. Eleven patients had positive TST exams with normal CXR exams prior to initiation of infliximab, 11 patients had currently or previously positive TST exams and/or abnormal CXR or chest CT findings (and most of them received treatment), and purified protein derivative (PPD) status was not determined in 4 patients who had normal CXR findings initially. Two patients who developed TB were not treated (one refused), and treatment was not reported in 4 patients who developed TB. Outcomes are reported for all but 8 patients. The information included in this section is summarized from published cases reported by the author(s) and has not been independently verified. The inclusion of published reports in this section should not be read to rule out the existence of other case reports of tuberculosis, published or otherwise.11596, 11869, 11870, 11871, 11872, 11873, 11874, 11875, 11876, 11877, 11878, 11879, 11880, 11882, 11883, 11884, 11885, 11886, 11887, 11888, 11889, 11890, 11891, 11892, 11893, 11894, 11895, 11954, 11955, 12418, 12419, 12420, 12421, 12447, 12448, 12449, 12450, 12457, 12473
| Age Gender Disease State (AS, CD, PsA, PsO, RA, UC) Disease Duration Publication | Dose of Infliximab/ Regimen/ Duration of Therapy | Other Immuno- suppressant Medication History | Diagnostic Assessments and Treatment | Outcome(s) |
|---|---|---|---|---|
|
22-y-old Female AS 34 mo Cooper 200912418 |
|
History of: Corticosteroids Concomitant medication: MTX Corticosteroids |
Possible TB exposure as a child TST and CXR negative in 2003 prior to start of infliximab treatment Admitted to hospital with moderate abdominal pain, and elevated ESR and CRP levels; last dose given 10 days prior to admission; corticosteroids last given 12 wk prior Patient reported Terminal ileitis confirmed on CT and colonoscopy and budesonide started;
fever to Clostridium toxin, Yersinia, Salmonella, Campylobacter and CMV all negative Follow-up abdominal CT showed multiple mesenteric and parailiacal lymph nodes with progressive small bowel distension due to stenosis of the jejunum and terminal ileum Widespread granulomatous peritoneal lesions and 2 tumors with small bowel stenosis on surgery Segmental stenosis of jejunum and ileocecum on resection Extensive transmural granulomatous epithelioid inflammation with giant cells, superficial ulcerations, granulocytic microabscesses, and caseating necrosis on histopathology Granulomatous inflammations with necrosis and scarring of several mesenteric lymph nodes MTB DNA of terminal ileum and lymph nodes on PCR PCR negative for atypical mycobacteria, Yersinia enterocolitica, and
AFB negative Cultures of resected material not performed Treatment included: RIPE for 4 mo, then rifampin, pyrazinamide, and ethambutol for another 4 mo |
Infliximab discontinued and other Patient followed for |
|
23-y-old Male AS Disease Duration not reported Iliopoulos 200611869 |
|
Not reported |
TST positive 9 mo prior to admission with normal CXR INH, CXR and chest CT on admission showed LLL consolidation Findings of LLL endobronchial TB AFB stains and cultures positive for MTB Caseating granulomas on histology Treatment included: 5-drug |
Treated successfully |
|
48-y-old Female AS Disease Duration not reported Iliopoulos 200611869 |
|
Not reported |
No prior history of TB PPD normal and CXR prior to initiation of infliximab unremarkable Development of diffuse abdominal
pain and low grade fever Ascitic fluid and right ovarian cystic lesion on abdominal ultrasound Right-sided metastatic lesions on abdominal CT scan Caseating granulomas on histological exam of ovaries and greater omentum Treatment included: 3-drug anti-TB regimen, not specified |
Treated successfully for TB although ovarian cancer was also diagnosed |
|
50-y-old Female AS Disease Duration not reported Sichletidis 200612447 |
Not reported |
Concomitant medication: Corticosteroids MTX |
Upon initial screening TST negative and CXR normal TB developed 12 mo after initial infliximab dose Lymph nodes were site of active TB Per the publication diagnosis established by either sputum exam or by histopathologic exam of biopsy specimens Isolate susceptible to all Infliximab stopped immediately Unspecified treatment for active TB given |
Not reported |
|
54-y-old Male AS Disease Duration not reported Sichletidis 200612447 |
Not reported |
Concomitant medication: Corticosteroids MTX |
Patient had a positive screening TST and a negative CXR Patient prescribed INH x 6 mo TB developed 3 mo after initial infliximab dose Pulmonary site of active TB Per publication diagnosis established by either sputum exam or by histopathologic exam of biopsy specimens Isolate susceptible to all Infliximab stopped immediately Unspecified treatment for active TB given |
Not reported |
|
56-y-old Male AS Disease Duration not reported Garcia Vidal 200512448 |
Amount not specified x 2 mo |
Not reported |
Per the publication, patient had no prior history of TB and screened PPD negative Infliximab started September 2001; patient admitted with fever, dyspnea,
and cough Clinical manifestations of pulmonary and pleural TB, evidenced by RUL infiltrate and bilateral pleural effusions on CXR AFB-positive sputum smear; culture not done MTB susceptible to all drugs recovered from pleural fluid culture Anti-TB meds initiated and infliximab stopped TB disease flare 2 mo later; CT revealed progression of previous infiltrates, new cavitated infiltrate, and persistent pleural effusions AFB-positive repeat sputum smear Prednisone added to regimen, with excellent clinical response Treatment included: INH Rifampin Pyrazinamide Prednisone |
Anti-TB treatment given for 1 y, with complete resolution of TB Patient followed
up for an additional |
|
42-y-old Male CD 13 y Bourikas 200811870 |
|
Concomitant medication: AZA |
INH for positive TST started Patient admitted with high fever up
to Miliary TB on chest CT Left occipitoparietal lesion without abscess on MRI TB on right lung biopsy Treatment included: Levofloxacin Rifampin Pyrazinamide Ethambutol |
Empiric treatment with levofloxacin Clinical and radiologic improvement during the |
|
24-y-old Male CD 7 y Arend 200711871 |
Amount not specified x 4 doses |
History of: AZA Corticosteroids Concomitant medication: Corticosteroids |
Patient had a negative TST and normal
CXR upon screening prior to QuantiFeron-TB Gold assay positive Acid-fast staining and PCR of BAL fluid negative for MTB BACTEC MGIT 960 culture fully positive for MTB Mediastinal lymphadenopathy on CXR Multiple intrapulmonary miliary nodules on chest CT Auramine positive sputum Treatment included: INH Rifampin Pyrazinamide Ethambutol |
Further weight loss Development of immune reconstitution syndrome 1 mo after beginning treatment Persistent radiographic abnormalities after Gradual discontinuation of all immunosuppressive medications |
|
68-y-old Male CD 19 y Stas 200612449 |
5 mg/kg |
History of: Corticosteroids AZA Concomitant medication: AZA |
Patient referred for diarrhea, anorexia, weight loss, progressive dyspnea, edema of the lower limbs, and progressive liver dysfunction Patient had a negative
TST and a CXR with minor changes consistent with pneumoconiosis from
his Patient given a 3-dose induction regimen with good effect and drainage of fistula; subsequently started on maintenance therapy, with last infusion given 6 wks prior to admission Progressive liver dysfunction noted 6 mo prior to admission Vanishing bile duct disease suggested on ERCP Patient admitted with cachexia, fever, signs of dehydration, tachycardia, and signs of hypoventilation at the left lung base Left-sided pleural effusion and diffuse reticulonodular infiltrate on CXR; fluid transudative on lung puncture Predominance of lymphocytes on cytologic exam; sterile culture Negative Ziehl-Neelsen stain and Löwenstein-Jensen culture Diffuse enteritis with multiple enterocutaneous fistulas, limited ascites, and mesenteric adenopathies on abdominal CT Midsigmoid stenosis and possible enterocolic fistula on barium enema Hemocultures remained sterile during hospitalization; stool and urine cultures negative Plethora of bacteria noted on culture of enterocutaneous fistula orifice AZA stopped and patient treated with levofloxacin and ornidazole, and total parenteral nutrition with slow improvement Patient improved slowly but continued to have fevers, dyspnea, and recurrent pleural effusions on CXR Ascites and numerous small white nodules and plaques seen on laparotomy, compatible with granulomatous disease TB confirmed by microscopy and positive Ziehl-Neelsen staining Granulomatous hepatitis on liver biopsy; sterile abdominal fluid Repeat Ziehl-Neelsen stain and Löwenstein-Jensen culture negative Treatment included: INH with pyridoxine Rifampicin Amikacin Ethambutol Rifampicin replaced by pyrazinamide because of progressive liver dysfunction |
Postoperative course complicated by difficult weaning for which tracheostomy was necessary Patient discharged |
|
21-y-old Male CD Disease Duration not reported Garcia Vidal 200512448 |
Amount not specified x 1 mo |
Not reported |
Per the publication, patient had no prior history of TB and screened PPD negative Infliximab started May 2001; patient admitted with fever and intersphincteric fistula recurrence 4 wk later Repeat PPD positive, CXR normal AFB observed in anal ulcer exudates, and cultures of exudates yielded MTB susceptible to all drugs Anti-TB drugs started and infliximab discontinued; 4 mo later patient with fever, malaise, persistent anal ulcer, and progressive increase in the size of the inguinal lymph nodes Caseating granulomas on biopsy; culture results negative Patient diagnosed with paradoxical reaction and treatment with an NSAID started; lymphadenopathic mass progressively improved Treatment included: INH Rifampin Pyrazinamide Unspecified NSAID |
Patient completed Patient followed up for an additional |
|
54-y-old Female CD Disease Duration not reported Costamagna 200411872 |
Amount not specified x 2 doses |
Not reported |
TST positive in 1996, untreated upper-lobe lung nodules with pleural effusion on CXR 2 wk after Upper-lobe lung nodules with pleural effusion on CXR MTB positive sputum specimens Treatment included: INH Rifampin Pyrazinamide Ethambutol |
INH discontinued due to GI intolerance; patient continued treatment with other anti-TB meds Per the publication, patient free of TB disease |
|
46-y-old Female CD 2 y Wagner 200211954 |
|
History of: Mesalamine Corticosteroids |
History of pulmonary TB at 2-wk
history of fevers, chills, drenching night sweats, blood-streaked
loose stools, and epigastric pain which began CXR findings consistent with prior TB infection, unchanged from 1997 Segmental inflammatory disease with innumerable pseudopolyps on colonoscopy; caseating granulomas on biopsy specimens Focal strictures, involvement of ileocecal region on barium enema Treatment included: TB in childhood untreated Rifampin INH Ethambutol Pyrazinamide Pyridoxine |
Excellent clinical response to TB treatment |
|
68-y-old Male CD Disease Duration not reported Keane 200111873 |
Amount not specified x 1 dose (patient was the index patient for cases of TB identified through the FDA database) |
Not reported |
Per the publication, complete information about the status of the patient with respect to TB infection prior to infliximab therapy is not known Developed
symptoms Pulmonary fibrosis on thoracic CT, not present on previous thoracic CT Idiopathic pulmonary fibrosis with lymphocyte infiltration on histopathologic exam of an open-lung biopsy; no granulomas present MTB positive sputum No AFB seen in the biopsy specimen Treatment not reported |
Not reported |
|
53-y-old Male CD 25 y Nuñez Martinez 200111874 |
|
History of: Aminosalicylates Corticosteroids |
Details of initial screening and/or prophylaxis not provided, however, evidence of old TB on CXR revealed after pt admitted with symptoms 5 days post 1st CXR showed images compatible with TB sequelae in upper lobes Next CXR revealed a right pleural effusion in addition to previous findings Acid-alcohol resistant rods on fibrobronchoscopy with bronchoalveolar wash MTB positive urine culture Treatment not reported |
Clinical improvement |
|
62-y-old Female PsA Disease Duration not reported Sichletidis 200612447 |
Not reported |
Concomitant medication: Corticosteroids |
Patient had a positive screening TST and
a negative CXR, and as per the publication was prescribed either INH
x TB developed 8 mo after initial infliximab dose Nasopharynx site of active TB Per publication diagnosis established by either sputum exam or histopathologic exam of biopsy specimens Isolate susceptible to all Infliximab stopped immediately Unspecified treatment for active TB given |
Not reported |
|
49-y-old Female PsA Disease Duration not reported Sichletidis 200612447 |
Not reported |
Concomitant medication: Corticosteroids |
Patient had a positive screening TST and
a negative CXR and as per the publication was prescribed either INH
x TB developed 35 mo after initial infliximab dose Pulmonary site of active TB Per publication diagnosis established by either sputum exam or by histopathologic exam of biopsy specimens Isolate susceptible to all Infliximab stopped immediately Unspecified treatment for active TB given |
Not reported |
|
65-y-old Male PsA Disease Duration not reported Baeten 200311596 |
|
Concomitant medication: Corticosteroids |
Per the publication, patient did not have a personal or family history of TB prior to start of infliximab therapy Paper did not state whether patient was screened or prophylaxed for latent TB, but states that at that time patients were not screened systematically with skin testing and CXR before the start of infliximab therapy Developed
high fever, general malaise, and increasing inflammatory parameters Possible nodular lesions of liver and spleen on CT, as well as mediastinal lymphadenopathies Histology and culture of mediastinal lymph node biopsy specimens Treatment included: INH Rifampin Pyrazinamide Ethambutol |
Dissemination of TB disease Patient recovered from TB |
|
56-y-old Male PsA 12 y Liberopoulos 200211875 |
|
History of: MTX Corticosteroids Concomitant medication: MTX Corticosteroids |
Per the publication, patient did not have a past history of TB nor had he been exposed recently to a person with known active disease Screening PPD and CXR were negative for the presence of active or latent TB 10 wk after the start of infliximab patient developed fever, productive cough, and nocturnal diaphoresis Chest CT with multiple, bilateral small nodules Abdominal CT with diffuse lymphadenopathy, hepatomegaly, multiple hypodense regions within the spleen, and infiltration of the kidneys and adrenal glands Lymphoid inflammation and profound necrosis on liver and bone marrow biopsy specimens AFB- positive sputum MTB- positive PCR Treatment included: INH Rifampin Pyrazinamide Pyridoxine |
Development of multiple organ failure and death 25 days after admission |
|
31-y-old Male PsO/PsA Disease Duration not reported Perlmutter 200912419 |
Amount not specified x 9 mo |
History of: Other anti-TNF started in August 2004, then discontinued in 2005 |
PPD and CXR negative in 2003 and 2004; BCG status unknown PPD positive 1 y later
with INH therapy provided that was described as adequate although dose and duration not provided Other Infliximab subsequently started until development of general malaise, headaches, and low grade fevers 9 mo later Mildly elevated CRP Thickened proximal jejunum and distal duodenum on abdominal CT Hospitalized for dehydration, then had newly elevated LFTs with normal total bilirubin Lymphocytic meningitis with elevated protein on CSF studies Negative for AFB by smear, culture, and PCR Mediastinal lymphadenopathy on chest CT with RIPE therapy initiated for disseminated TB and presumptive TB meningitis Treatment included: INH Rifampin Pyrazinamide Ethambutol |
Not reported |
|
65-y-old Male PsO/PsA Disease duration not reported Perlmutter 200912419 |
Amount not specified x 3 infusions |
History of: Other |
On presentation, PPD positive at 15 mm induration with CXR negative; patient started on INH Other anti-TNF therapy started 3 mo later and continued for 10 mo until return of PsO activity Infliximab subsequently started, then patient hospitalized for generalized lethargy, somnolence, and cough after 3rd infusion Numerous bilateral miliary pulmonary nodules suggestive of TB on CXR despite INH prophylaxis On thoracoscopy with biopsy, presence of caseating granulomas, positive AFB stains, cultures, and DNA probe for mycobacterium complex Patient started on RIPE therapy Treatment included: INH Rifampin Pyrazinamide Ethambutol |
Not reported |
|
Age not reported Male PsO Disease Duration not reported Krathen 200612479 |
5 mg/kg x 2 doses |
Not reported |
Baseline PPD positive, old granulomas visible on CXR prior to start of therapy Paper does not state whether patient was prophylaxed for latent TB Patient reported adequate treatment for TB 20 y earlier Infliximab discontinued after 2nd infliximab infusion following reactivation of TB Treatment not reported |
Not reported |
|
39-y-old Male PsO Disease Duration not reported Smith 200612473 |
Amount not specified x 3 doses |
History of: MTX Mycophenolate mofetil Concomitant medication: MTX Mycophenolate mofetil |
Baseline CXR normal, visible BCG scar Screening PPD information not provided, and per the publication, patient had frequent travel to India PsO cleared with infliximab but 3 wk after 3rd dose patient admitted to a local hospital with epistaxis and a swinging fever Profound thrombocytopenia on investigation; cleared 1 mo later after treatment with pooled IVIG immunoglobulin, and infliximab permanently discontinued Fever improved while patient in hospital, but no source of infection identified; PsO continued to be managed conservatively Patient admitted 6 mo later with increasing malaise, joint pains, and fever Normal CXR and echocardiogram; supraclavicular, mediastinal and hilar lymphadenopathy on CT Large splenic abscess on abdominal ultrasound and MTB isolated from pus aspirated from abscess Treatment included: Quadruple therapy, not specified |
Patient completed |
|
41-y-old Male PsO/PsA Disease Duration not reported Crum 200512457 |
Amount not specified x 4 doses |
History of: Other Corticosteroids |
Paper does not state whether patient was screened or prophylaxed for latent TB prior to infliximab therapy Presented with fever of unknown origin in May 2002, after 4th infliximab dose Treated with other anti-TNF therapy from September to December 2001, followed by infliximab in March to May of 2002 Infliximab discontinued in May 2002 and corticosteroids added Latent TB in 1986, treated with 6 mo course of INH Multiple evaluations for fever from May to October 2002; all CXRs, blood and sputum cultures, malaria smears, and serologies for coccidioidomycosis, cryptococcosis, strongyloidiasis, and brucellosis negative Unintentional 16 kg weight loss and patient referred to a gastroenterologist for possible gastrointestinal TB; colonoscopy and biopsies negative Admitted with cough and persistent fevers in October 2002 Cavitary RUL mass, numerous bilateral upper lobe nodules, endobronchial lesions, mediastinal and supraclavicular adenopathy, multiple splenic lesions, and solitary liver and kidney lesions on chest CT MTB on BAL Started on 4-drug therapy; isolate later INH-resistant and patient subsequently treated with rifampin, ethambutol, and pyrazinamide Treatment included: INH Rifampin Pyrazinamide Ethambutol |
Patient restarted on infliximab in March 2003, then switched to other biologic therapy TB medications continued for an Persistent bilateral upper lobe nodules on most recent CXR At time of report, patient remained on a monoclonal antibody and was doing well at last follow-up |
|
42-y-old Female RA 9 y Garcia-Vidal 200912452 |
15 mg/kg total dose given |
History of: MTX Corticosteroids Gold Chloroquine Concomitant medication: MTX Corticosteroids |
Manifestation of extrapulmonary and disseminated TB Peritoneal biopsy and sputum culture positive TB diagnosed 10 mo after initial dose of infliximab given PPD status at baseline was not determined; initial CXRs normal Treatment included: INH Rifampin Pyrazinamide Ethambutol |
Patient reportedly cured of TB |
|
48-y-old Female RA 7 y Garcia-Vidal 200912450 |
60 mg/kg total dose given |
History of: MTX Corticosteroids Cyclosporin Concomitant medication: MTX |
Manifestation of miliary and lymph node disease Lymph node biopsy positive TB diagnosed 34 mo after initial dose of infliximab given PPD status at baseline was not determined; initial CXRs normal Treatment included: INH Rifampin Pyrazinamide Ethambutol |
Patient reportedly cured of TB |
|
49-y-old Female RA 20 y Garcia-Vidal 200912452 |
12 mg/kg total dose given |
History of: MTX Sulfasalazine Gold Chloroquine D-penicillamine Concomitant medication: MTX Corticosteroids |
Manifestation of miliary and lymph node disease Lymph node biopsy and sputum culture positive TB diagnosed 2 mo after initial dose of infliximab given PPD status at baseline was not determined; initial CXRs normal Treatment included: INH Rifampin Pyrazinamide |
Patient reportedly cured of TB |
|
51-y-old Female RA 9 y Garcia-Vidal 200912452 |
12 mg/kg total dose given |
History of: MTX Corticosteroids AZA Concomitant medication: MTX |
Manifestation of miliary and lymph node disease Lymph node biopsy positive TB diagnosed 2 mo after initial dose of infliximab given PPD status and booster test negative; initial CXRs normal Treatment included: INH Rifampin Pyrazinamide |
Patient reportedly cured of TB |
|
65-y-old Male RA 3 y Hirano 200912420 |
200 mg/infusion x 18 infusions |
History of: MTX Mizoribine Corticosteroids Concomitant medication: MTX Mizoribine Corticosteroids |
Screening TST positive, with normal Screening CXR and chest CT normal Maternal history of lung TB when patient was 20 y old Anti-TB
chemoprophylaxis with INH Total knee arthroplasty performed and patient’s glucose tolerance deteriorated INH continued for 9 mo and no TB detected Onset of lung TB after 18th infliximab infusion, 17 mo after last INH dose Patient presented with weight loss, mild cough, sputum, and normal body temperature in November 2006 Patient had episodes of Consolidation and cavitation on chest CT consistent with lung TB or abscesses Sputum test Patient diagnosed with active TB via positive sputum, started on RIPE therapy, then switched to INH, rifampin, and ethambutol Improved LUL consolidation on CXR; follow up sputum negative Treatment included: INH Rifampin Pyrazinamide Ethambutol |
Patient subsequently discharged from hospital and treated with anti-TB meds prescribed by respiratory medicine specialists Chest CT at time of last follow-up showed pleural thickening with disappearance of consolidation MTB strain was not resistant to all anti-TB drugs |
|
73-y-old Female RA Disease Duration not reported Asano 200811876 |
Amount not specified x 4 doses |
History of: Corticosteroids MTX Concomitant medication: Corticosteroids MTX |
According to the case history provided, the patient was not screened for TB prior to the start of infliximab therapy 3rd mo after
infliximab therapy, patient febrile Epithelioid cell granulomas with prominent caseation necrosis and many Langhans’-type giant cells on skin biopsy Numerous AFB on PCR-detected MTB on skin and sputum specimens Nodules and bilateral infiltrates on CXR and chest CT Treatment included: INH Rifampin Pyrazinamide Ethambutol |
Resolution of both cutaneous and pulmonary lesions after 5 mo of anti-TB therapy |
|
68-y-old Female RA 21 y Verhave 200811877 |
Amount not specified x 3 doses initially; stopped after patient developed TB, then restarted 1 mo later x 4 y |
Not reported |
According to the case history provided, the patient was not screened for TB prior to the start of infliximab therapy Patient developed TB after receiving 3 infusions of infliximab in 2002, and was treated with INH for 6 mo Infliximab infusions were interrupted for 1 mo and resumed at 8 weekly intervals thereafter Patient hospitalized in 2006 with progressive lower
abdominal pain, fever and weight loss of Ascites and swollen omentum on abdominal ultrasound Peritoneal biopsy with inflammation without granulomas or malignancy Treatment included: When no apparent cause for peritonitis could be identified, anti-TB regimen started Piperacillin/tazobactam |
Clinical condition improved after several
wk and patient returned home after 3 mo later, peritoneal biopsy culture positive for MTB |
|
53-y-old Female RA Disease Duration not reported Verhave 2008 11877 |
Amount not specified x 3 mo |
History of: MTX Corticosteroids Concomitant medication: MTX Corticosteroids |
Screening PPD negative prior to start of infliximab therapy 3 mo after infliximab therapy started, abdominal pain occurred Initial CXR negative MTB positive ascites Developed asymptomatic miliary TB on CXR after Two Treatment included: INH Rifampin Levofloxacin Pyrazinamide (later switched to Ethambutol after hepatitis developed) |
Hepatitis developed and TB meds stopped after 3 mo Development of asymptomatic military TB on CXR during re-introduction of anti-TB medications Development of 2 auramine-negative PCR-positive supraclavicular tumors after 7 mo of TB therapy TB therapy halted after 1 y of treatment and patient doing well |
|
54-y-old Female RA 15 y Burr 200811878 |
Amount not specified x 42 mo |
History of: Sulfasalazine Cyclosporine A MTX Concomitant medication: Corticosteroids MTX |
Per the publication, patient had no known history of TB and screening CXR prior to infliximab therapy was normal Patient recalled a positive TST 30 y previously, but paper does not state whether patient received treatment for this positive TST Fever, night sweats, and lethargy
x CT of chest, abdomen, and pelvis suggestive of granulomatous disease AFB on BAL and transbronchial biopsy Treatment included: Ethambutol Rifampin Pyrazinamide INH (later switched to moxifloxacin due to INH-resistant strain of MTB) |
Completed extended anti-TB course in April 2007 |
|
78-y-old Female RA Disease Duration not reported Karagiannis 200811879 |
Amount not specified x 18 mo |
Not reported |
Per the publication, patient reported no history of TB Paper does not state whether patient was screened or prophylaxed for latent TB Well-defined epithelioid granulomas in the mucosa, with numerous AFB on histology PCR positive biopsy specimens Treatment included: INH Rifampin Ethambutol with pyridoxine |
Partial enteric obstruction |
|
73-y-old Female RA 20 y Aslanidis 200811880 |
Amount not specified x 6 mo |
History of: MTX No concomitant medications given |
Publication states that 4 of the 5 patients
in this group had a negative Patient subsequently received
infliximab x Diagnosis was established by clinical and radiographic criteria, as well as response to treatment, and TB was considered to be reactivation of latent disease Treatment included: Ethambutol x Rifampin/INH x Low-dose corticosteroids given during TB treatment
phase with |
Recovered within 6 to |
|
63-y-old Male RA 7 y Aslanidis 200811880 |
Amount not specified x 46 mo |
History of: MTX No concomitant medications given |
Publication states that 4 of the 5 patients
in this group had a negative Patient subsequently received
infliximab x Diagnosis was established by clinical and radiographic criteria, as well as response to treatment, and TB was considered to represent new onset disease Treatment included: Streptomycin x Ethambutol x Rifampin/INH x Low-dose corticosteroids given during TB treatment phase with reinitiation of MTX |
Recovered within 6 to RA disease flare No evidence of TB relapse |
|
63-y-old Female RA 23 y Aslanidis 200811880 |
Amount not specified x 2 mo |
History of: MTX No concomitant medications given |
Publication states that 4 of the 5 patients
in this group had a negative Patient subsequently received
infliximab x Diagnosis was established by lymph node biopsy, and TB was considered to be reactivation of latent disease Treatment included: Ethambutol
x INH/Rifampin
x Low-dose corticosteroids given during TB treatment phase with reinitiation of MTX |
Recovered within 6 to 12 mo RA disease flare Patient restarted on a different anti- TNF agent due to a mild allergic reaction to infliximab No evidence of TB relapse |
|
79-y-old Female RA 15 y Aslanidis 200811880 |
Amount not specified x 5 mo |
History of: MTX No concomitant medications given |
Publication states that 4 of the 5 patients
in this group had a negative Patient subsequently received
infliximab x Diagnosed was established by sputum culture, and TB was considered to be reactivation of latent disease Treatment included: Streptomycin
x Ethambutol
x INH x Low-dose corticosteroids given during TB treatment phase with reinitiation of MTX |
Recovered within 6 to |
|
64-y-old Female RA 10 y Aslanidis 200811880 |
Amount not specified x 4 mo |
History of: MTX Anti-TNF therapy No concomitant medications given |
Publication states that 4 of the 5 patients
in this group had a negative Patient received infliximab
x Diagnosis was established by bronchoscopy and lung biopsy, and TB was considered to be representative of new onset disease Treatment included: Streptomycin x Ethambutol x Rifampin/INH x Low-dose corticosteroids given during TB treatment phase with re-initiation of MTX |
Recovered from TB within 6 to No evidence of TB relapse |
|
51-y-old Female RA Disease Duration not reported Seong 200711955 |
Amount not specified x 8 mo |
History of: MTX Cyclosporine Bucillamine |
Per the publication, patient had no history of contact with active TB patients TST positive at baseline and no prophylaxis given Bronchiectasis on CXR Biopsy Treatment not reported |
Not reported |
|
34-y-old Male RA Disease Duration not reported Seong 200711955 |
Amount not specified x 4 mo |
History of: MTX Hydroxychloro- quine Sulfasalazine Corticosteroids |
Baseline TST negative and CXR normal Patient developed AFB positive miliary TB Treatment not reported |
Not reported |
|
58-y-old Male RA 3 y Raychaudhuri 200711882 |
|
History of: MTX Sulfasalazine Corticosteroids Concomitant medication: MTX Sulfasalazine |
TST positive Admitted with No new infiltrates or pathologic lymphadenopathy on follow-up CXR or chest CT Abdominal and pelvic CT scan revealed enlarged mesenteric and retroperitoneal nodes Sputum cultures grew MTB 9 days after patient discharged Treatment included: INH Rifampin Pyrazinamide Ethambutol |
Full recovery |
|
77-y-old Female RA Disease Duration not reported Raychaudhuri 200711882 |
|
History of: MTX Leflunomide Corticosteroids Concomitant medication: MTX Corticosteroids |
TST positive Seven y prior to admission patient treated with INH for 7 mo TST negative Patient started on infliximab 4 mo prior to admission Paper does not state whether patient was screened or prophylaxed for latent TB again immediately prior to infliximab therapy Admitted with a
Profoundly weak with slurred speech on admission LLL pneumonia on CXR Miliary TB on chest CT Sputum sample positive by gen-probe amplified mycobacterium TB direct test MTB positive sputum cultures Treatment included:
Levofloxacin (treatment of community-acquired pneumonia) Rifampin INH Ethambutol Pyrazinamide |
Developed respiratory failure requiring mechanical ventilation x 9 days Gradual recovery with discharge to rehabilitation facility after a 34-day hospital course |
|
67-y-old Female RA 17 y Iliopoulos 200611869 |
|
History of: MTX Leflunomide |
Patient had a negative TST and normal CXR at baseline, with no history of TB 15 days after last dose of infliximab, admitted with weakness, weight
loss, and fever up to Multiple caseating granulomas on biopsy and histology of cervical lymph nodes TB-positive PCR Treatment included: 3 drug anti-TB regimen, not specified |
Treated successfully |
|
64-y-old Female RA 10 y Matsumoto 200611883 |
|
Concomitant medication: Corticosteroids Sulfasalazine MTX |
Patient had a nonreactive TST and normal CXR at baseline Developed high fever and
abdominal distension after MTB collected from peritoneal fluid Treatment included: INH Rifampin Pyrazinamide Ethambutol |
Resolution of clinical signs and symptoms of peritoneal TB, and a highly symptomatic RA flare 4 mo later Infliximab restarted in conjunction with No signs of TB recurrence detected after more than a y of follow-up |
|
67-y-old Female RA Disease Duration reported as long standing. Lesnik 200611884 |
Amount not specified x 3 mo |
History of: Corticosteroids MTX |
Patient had a negative TST and no risk factors for TB at baseline 3 mo after initiation
of infliximab therapy, patient developed a fever in excess of Irregular thickening of transverse colon, homogeneous attenuation on CT of abdomen Hypoechoic, homogeneous colonic wall thickening on abdominal ultrasound Biopsy revealed granu- lomatous tuberculoma of the chorion MTB detected through bacteriologic sampling and cultures Treatment included: Standard 4-drug anti-TB regimen, not specified |
Fever and weight loss controlled on anti-TB regimen Decrease in bowel wall thickening
on follow-up CT exam |
|
66-y-old Female RA 9 y Imaizumi 200611885 |
|
History of: MTX Corticosteroids Concomitant medication: MTX |
Patient had a negative TST prior to start of infliximab therapy, and she had no history of TB Fever, anorexia, diarrhea, and general malaise developed Bilateral pleural effusion and remarkable bilateral hilar and mediastinal lymphadenopathy on CXR and chest CT along with small nodular opacities in the right middle and lower lobes Transbronchial
needle aspiration biopsy of a AFB positive Ziehl-Neelsen stain of necrotizing tissue PCR positive for TB Treatment included: INH Rifampin Ethambutol Pyrazinamide |
After Hilar and mediastinal lymphadenopathy and bilateral pleural effusion on chest CT resolved 3 mo after treatment Initiation |
|
43-y-old Male RA Disease Duration not reported Sichletidis 200612447 |
Not reported |
Concomitant medication: Corticosteroids MTX |
Patient had a positive screening TST and
apical fibrotic lesions with pleural calcification on CXR, and as
per the publication was prescribed either INH x Active TB developed Pulmonary site of active TB Per the publication, diagnosis established by either sputum exam or by histopathologic exam of biopsy specimens Isolate susceptible to all Infliximab stopped immediately Unspecified treatment for active TB given |
Not reported |
|
60-y-old Female RA Disease Duration not reported Sichletidis 200612447 |
Not reported |
Concomitant medication: MTX |
Patient had a positive screening TST and
negative CXR and as per publication was prescribed either TB developed 3 mo after initial infliximab dose Pleural effusion site of active TB Per publication diagnosis established by either sputum exam or histopathologic exam of biopsy specimens Isolate susceptible to all Infliximab stopped immediately Unspecified treatment for active TB given |
Not reported |
|
52-y-old Female RA Disease Duration not reported Sichletidis 200612447 |
Not reported |
Concomitant medication: Corticosteroids MTX |
Patient had a positive screening TST and
apical fibrotic lesions on CXR and as per publication was prescribed
either TB developed 2 mo after initial infliximab dose Pulmonary site of active TB Per the publication diagnosis established by either sputum exam or histopathologic exam of biopsy specimens Isolate susceptible to all Infliximab stopped immediately Unspecified treatment for active TB given |
Not reported |
|
63-y-old Female RA Disease Duration not reported Sichletidis 200612447 |
Not reported |
Concomitant medication: Corticosteroids MTX |
Patient had a positive screening TST and negative CXR and as per the publication, patient refused prophylactic treatment TB developed 18 mo after initial infliximab dose Spleen site of active TB Per the publication diagnosis established by either sputum exam or histopathologic exam of biopsy specimens Isolate susceptible to all Infliximab stopped immediately Unspecified treatment for active TB given |
Not reported |
|
49-y-old Female RA Disease Duration not reported Garcia Vidal 200512452 |
Amount not specified x 2 mo |
Not reported |
Per the publication, patient had no prior history of TB and screened PPD negative Infliximab started February 2002; patient admitted with fever, night sweats, and cough 2 mo later Left supraclavicular adenopathy on exam; CXR suggestive of miliary disease Multiple bilateral small nodules in the lung parenchyma on CT scan of thorax AFB in BAL fluid specimen Caseating granulomas on transbronchial biopsy MTB cultures positive and susceptible to all drugs Infliximab discontinued and anti-TB
drugs started with progressive improvement; Surgical excision of mass performed Caseating granulomas documented; culture results negative Treatment included: INH Rifampin Pyrazinamide |
Patient recovered uneventfully after full 9-mo course of treatment Patient followed up for an additional 3 mo |
|
48-y-old Female RA Disease Duration not reported Garcia-Vidal 200512452 |
Amount not specified x 24 mo |
Concomitant medication: MTX |
Per the publication, patient had no prior history of TB and screened PPD negative Infliximab and MTX started February 2000; patient admitted with fever and night sweats 24 mo later, following 18th dose Supraclavicular lymph node on exam Multiple bilateral, small pulmonary nodules consistent with TB on CT scan of thorax Sputum smears and cultures negative Anti-TB drugs started and infliximab discontinued; 2 mo later patient with progressive increase in the size of the cervical lymph nodes Patient eventually required excision of lymphadenopathic mass Caseating granulomas on biopsy of cervical lymph nodes; culture results yielded MTB susceptible to all drugs Treatment included: INH Rifampin Pyrazinamide Ethambutol |
Complete resolution of symptoms after 9-mo course of treatment; however, 10 mo after completion of treatment, while still off infliximab therapy, patient presented with fever and abdominal pain Presence of Caseating granulomas on lymph node biopsy; repeat cultures MTB positive As of January 31, 2005, treatment ongoing and patient doing well |
|
55-y-old Male RA Disease Duration not reported Costamagna 200411872 |
Amount not specified x 13 doses over 17 mo (September 2000-January 2002) |
Not reported |
Previously TST positive in 1995 and treated
with Paper does not state whether the patient was screened or prophylaxed for latent TB again prior to the start of infliximab therapy Infliximab therapy begun September 2000 Presented with fever and weight loss in January 2002 Enlargement of supraclavicular lymph
node Right upper-lobe cavity with nodular infiltrate on CXR MTB on sputum and lymph node specimens Treatment included: Anti-TB medications, not specified |
Condition improved on anti-TB medications Patient smoked for many y and was diagnosed
with lung cancer Patient died in November 2002 |
|
64-y-old Female RA Disease Duration not reported Costamagna 200411872 |
Amount not specified x 7 doses |
History of: Corticosteroids |
Exposure to person with drug-susceptible TB in 1999 with 2 subsequent negative TSTs in 2000, prior to the start of infliximab therapy Presented (April 2002) with fever and weight loss after 7th infusion Large pericardial effusion and right upper lobe infiltrate on CXR Sputum cultures and pericardial fluid both positive Treatment included: INH Rifampin Pyrazinamide Ethambutol Other anti-TB meds, not specified |
Patient’s TB resistant to all 4 first-line meds (isoniazid, rifampin, pyrazinamide, ethambutol) given Patient treated with second-line anti-TB meds x 12 mo and condition improved |
|
52-y-old Female RA 7 y Dimakou 200412421 |
3mg/kg |
History of: MTX Corticosteroids Concomitant medication: MTX Corticosteroids |
Although the history states that the patient
had a positive PPD skin test and negative CXR Admitted with 4-wk history of fevers, chills, anorexia, dry cough, and increasing dyspnea Infliximab started 8 mo prior to admission; patient complained of anorexia, malaise, and dry cough one mo after the 6th infusion, with elevation of body temperature to 38ºC during evening hours After treatment with oral loracarbef showed no improvement, patient seen in another hospital and diagnosed with bacterial respiratory infection, treated with cefuroxime axetil and roxithromycin Patient apyrexial for 2 days, then increasing dyspnea on exertion, fevers to 40ºC, and night sweats On admission, patient complained of dyspnea, nonproductive cough, and a burning sensation during urination CRP and ESR were elevated; rheumatoid factor, antinuclear antibodies, and anti-neutrophil cytoplasmic antibodies were normal LFTs elevated, with normal serum bilirubin, alkaline phosphatase, and gamma-glutamyl transpeptidase Trace protein and hemoglobin on urinalysis Hypoxemia on arterial blood gas analysis PPD positive with 20 mm induration Diffuse micronodular and interstitial densities of both lungs on admission CXR and chest CT TST positive 5 y prior, with normal CXRs Sputum, BAL, urine and gastric fluid samples following bronchoscopy, BAL and transbronchial biopsies all negative, with slight mucosal edema of bronchial tree on bronchoscopy Mononuclear cell infiltrate in interstitial tissue; no definitive formation of epithelioid granuloma and no evidence of caseous necrosis on lung histology Nondiagnostic bone marrow biopsy and choroidal tubercles on ophthalmologic consultation Treatment included: Ten day course of oral loracarbef Cefuroxime axetil and roxithromycin, both oral INH, rifampin, pyrazinamide, pyridoxine, and streptomycin started for miliary TB, also unspecified wide-spectrum antibiotics and oral corticosteroids Ethambutol, after streptomycin discontinued |
Initial improvement after start of anti-TB
regimen, but continued fever spikes to 39ºC for Streptomycin discontinued after Fever declined during 3rd wk of anti-TB therapy and patient apyrexial several days later Three gastric fluid cultures and 2 BAL and urine cultures positive for MTB using Bactec and MGIT system Patient discharged
and followed as an outpatient; free of respiratory and rheumatic symptoms Patient continued anti-TB therapy and corticosteroids |
|
58-y-old Female RA Disease Duration not reported |
|
Concomitant medication: MTX |
TST positive before start of therapy and
was treated with INH Admitted to ICU with somnolence, severe hyponatremia, fever, bilateral pulmonary infiltrates, and respiratory failure BAL with positive MTB positive bone marrow 2nd BAL on Herpes simplex virus type 2 cultured from abdominal and genital ulcerations Genital herpes on skin biopsy Treatment included: Corticosteroids given along with anti-TB meds Ethambutol INH Pyrazinamide Rifampin |
Initial improvement of symptoms, then
transferred to On Neurologic status improved Discharged post 63 days in ICU and 54 days of mechanical ventilation Transferred to rehabilitation facility but readmitted
to the hospital after After 4 mo of anti-TB treatment, MTB cultured from a metacarpal phalangeal joint of the right hand Article by Van der Kooij in 2009 indicated patient died of infectious complications |
|
65-y-old Female RA 3 y Parra Ruiz 200311891 |
Amount not specified x 11 doses (19 mo) |
History of: MTX AZA Sulfasalazine Hydroxychloro- quine Corticosteroids NSAIDs Concomitant medication: Corticosteroids AZA NSAIDs Sulfasalazine Hydroxychloro- quine Corticosteroids |
Previously Mantoux positive with no evidence of active TB; completed 6 mo of INH therapy prior to starting infliximab Persistent aseptic leukocyturia with MTB observed in urine culture Treatment included: Anti-TB drugs, not specified |
MTB isolate was not resistant to the |
|
65-y-old Male RA/PsO 10 y Taylor 200311892 |
Amount not specified x 1 y, then stopped secondary to development of minor allergic reaction during infusion Restarted after |
History of: MTX Sulfasalazine Corticosteroids No concomitant medications given |
Per the publication, patient had never had symptomatic TB nor received BCG vaccination CXR was normal and a Heaf test (a diagnostic TST) was grade 1 (considered normal) at baseline Patient started on infliximab and continued treatment for Developed dry cough and fevers Fiber-optic
bronchoscopies x 2 and open lung biopsy performed after Treatment included: Rifampin INH Pyrazinamide Ethambutol |
No response to anti-TB meds after Broad-spectrum antibiotics added (ceftazidime, levofloxacin, ami- kacin, and Augmentin) with no response initially Fever resolved
after |
|
63-y-old Female RA/OTH 10 y Rovere Querini 200211886 |
|
Concomitant medication: MTX Corticosteroids |
Per the publication, patient had a negative personal and family history of TB CXR at baseline was negative and the paper does not state whether a TST skin test was done 2 wk after last dose of infliximab,
patient developed intermittent fever of up to BAL cultures positive for MTB Miliary TB on CT scan of lungs, liver, and spleen Treatment included: Ethambutol INH Pyrazinamide Rifampin |
Partial success reported with anti-TB treatments and patient’s RA worsened |
|
48-y-old Female OTH 3 y Cordero-Coma 200811887 |
|
History of: Cyclosporine A Corticosteroids AZA Mycophenolate mofetil MTX Concomitant medication: AZA Corticosteroids |
Per the publication, demyelinating disease and TB ruled out prior to starting infliximab After Histopathologic analysis of resected intestinal tissue positive for MTB A Treatment included: Anti-TB treatment, not specified |
Patient died several days after anti-TB treatment initiated |
|
30-y-old Male OTH 4 y Mancini 200711888 |
|
History of: Corticosteroids Cyclosporine MTX
Chlorambucil AZA Concomitant medication: MTX during
a |
Paper does not state whether patient was screened or prophylaxed for latent TB Pulmonary
TB presented Specific assessments not reported 2 wk after Left upper lobe infiltration and diffuse pleural thickening with little pericardial effusion L pneumophila serotype 1 antigen detected in urine samples Treatment included: Antimicrobial chemotherapy, specific agents not reported Levofloxacin and rifampin
given for treatment of |
Treated successfully for TB initially,
and then for |
|
29-y-old Male OTH Disease Duration not reported Accorinti 200711889 |
Amount not specified x 3 doses |
History of: Cyclosporine A
Chlorambucil Colchicine Corticosteroids No concomitant medications given |
Prior to infliximab therapy, negative CXR and unremarkable PPD Pulmonary TB developed 2 mo after starting infliximab Specific diagnostic assessments not reported Treatment included: INH Ethambutol Piraldine Rifampin |
Treated successfully; complete resolution of pulmonary lesions |
|
43-y-old Male OTH 20 y Uthman 200411893 |
|
History of: Corticosteroids Cyclosporine No concomitant medications given |
PPD and CXR negative prior to start of infliximab therapy Low grade fever and
dry cough No infiltrates
on CXR taken on Caseating granulomas on pathology of transbronchial lung biopsy specimen Treatment included: INH Rifampin Ethambutol Pyrazinamide |
Resolution of fever and marked reduction
in severity of cough after Repeat x-ray 1 mo after start of treatment revealed marked decrease in size and number of previously described nodular opacities |
|
9-y-old Female OTH 4 y Armbrust 200411894 |
|
History of: Corticosteroids Indomethacin MTX Cyclosporine Concomitant medication: MTX and corticosteroids
with other anti-TNF agent from 2001 |
Paper does not state whether patient was screened or prophylaxed for latent TB Development of a cystic, subcutaneous swelling at the left wrist without signs of osteomyelitis; PCR positive MTB cystic fluid aspirated from left wrist Treatment included: Ethambutol INH Pyrazinamide Rifampin |
Removal of central venous line 1 mo after treatment for TB began, resulting in acute respiratory insufficiency and cardiac arrest Pulmonary embolism suspected and anticoagulation therapy started Death several hours later secondary to respiratory and circulatory failure |
|
54-y-old Male OTH Disease Duration not reported Baeten 200311596 |
|
Not reported |
Per the publication, patient did not have a personal or family history of TB prior to infliximab Paper did not state whether patient was screened or prophylaxed for latent TB, but states that at that time patients were not screened systematically with skin testing and CXR before the start of infliximab treatment Development of high fever, general malaise, and increasing inflammatory parameters 9 wk after start of infliximab treatment CT scan may have indicated nodular lesions in the liver and spleen, as well as mediastinal lymphadenopathies Histology and culture of mediastinal lymph node biopsy specimens Treatment included: INH Rifampin Pyrazinamide Ethambutol |
Dissemination of TB disease Patient recovered |
|
19-y-old Male OTH Disease Duration not reported Lim 200211895 |
|
Not reported |
Patient screened 20 mo prior to initiation of infliximab following close contact with a patient with smear-positive pulmonary TB, found to be negative Paper does not state whether patient was screened or prophylaxed for latent TB again prior to start of infliximab therapy Patient presented with 3-wk history of fever, sweats, dry cough,
and breathlessness 60 days after Upper and mid-zone interstitial lung shadowing with extensive lymphadenopathy on chest CT Heavy AFB infiltration on lymph node biopsy Treatment included: Rifampin Pyrazinamide INH |
Symptoms initially improved after anti-TB
medications begun, but then further temperature spikes occurred Patient’s T cells
able to make |
|
AFB=acid-fast bacilli; AS=ankylosing spondylitis; AZA=azathioprine;
BAL=bronchoalveolar lavage; BCG=Bacillus Calmette-Guérin; CD=Crohn’s
disease; CMV=cytomegalovirus; CRP=C-reactive protein; CSF=cerebrospinal
fluid; CT=computed tomography; CXR=chest x-ray; DIC=disseminated intravascular
coagulation; DNA=deoxyribonucleic acid; ICU=intensive care unit; ESR=erythrocyte
sedimentation rate; GI=gastrointestinal; IBD=inflammatory bowel disease;
INH=isoniazid; IV=intravenous therapy; LFTs=liver function tests;
LLL=left lower lobe; LTBI=latent tuberculosis infection; LUL=left
upper lobe; mo=month(s); MTB=mycobacterial tuberculosis; MTX=methotrexate;
NSAIDs=nonsteroidal anti-inflammatory drugs; OTH=other disease not
specified; PPD=purified protein derivative; PCR=polymerase chain reaction;
PsA=psoriatic arthritis; PsO=psoriasis; RA=rheumatoid arthritis; RIPE=rifampin,
isoniazid, pyrazinamide, ethambutol; RUL=right upper lobe; TB=tuberculosis;
TNF=tumor necrosis factor; TST=tuberculin skin test; UC=ulcerative
colitis; wk=week(s); x=for; | ||||
Content on this page was last reviewed on March 01, 2010.
Content on this page was last changed on July 01, 2010.
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| 11869. | Iliopoulos A, Psathakis K, Aslandis S, et al. Tuberculosis and granuloma formation in patients receiving anti-TNF therapy. Int J Tuberc Lung Dis. 2006;10(5):588-590. |
| 11870. | Bourikas LA, Kourbeti IS, Koutsopoulos AV, et al. Disseminated tuberculosis in a Crohn’s disease patient on anti-TNFα therapy despite chemoprophylaxis. Gut . 2008;57(3):425. |
| 11871. | Arend SM, Leyten EM, Franken WP, et al. A patient with de novo tuberculosis during anti-tumor necrosis factor-α therapy illustrating diagnostic pitfalls and paradoxical response to treatment. Clin Inf Dis. 2007;45(11):1470-1475. |
| 11872. | Centers for Disease Control and Prevention. Tuberculosis associated with blocking agents against tumor necrosis factor-alpha-California, 20022003. MMWR. Morb Mortal Wkly Rep 2004;53(30):683-686. |
| 11873. | Keane J, Gershon S, Wise RP, et al. Tuberculosis associated with infliximab, a tumor necrosis factor α-neutralizing agent. N Engl J Med. 2001;345(15):1098-1104. |
| 11874. | Núñez Martínez O, Ripoll Noiseux C, Carneros Martín JA, et al. Reactivation tuberculosis in a patient with anti-TNF-α treatment. Am J Gastroenterol. 2001;96(5):1665-1666. |
| 11875. | Liberopoulos EN, Drosos AA, Elisaf MS. Exacerbation of tuberculosis enteritis after treatment with infliximab. Am J Med . 2002;113(7):615. |
| 11876. | Asano Y, Kano Y, Shiohara T. Atypical cutaneous tuberculosis in a patient with rheumatoid arthritis treated with infliximab. Acta Derm Venereol . 2008;88(2):183-184. |
| 11877. | Verhave JC, van Altena R, Wijnands MJ, Roerdink HT. Tuberculous peritonitis during infliximab therapy. Neth J Med. 2008;66(2):77-80. |
| 11878. | Burr ML, Malaviya AP, Gaston JH, et al. Rituximab in rheumatoid arthritis following anti-TNF-associated tuberculosis. Rheumatology (Oxford). 2008;47(5):738-739. |
| 11879. | Karagiannis S, Papaioannou D, Goulas S, et al. Intestinal tuberculosis in a patient on infliximab treatment. Gastrointest Endosc . 2008;67(7):1178-1179. |
| 11880. | Aslanidis S, Pyrpasopoulou A, Douma S, et al. Is it safe to readminister tumor necrosis factor α antagonists following tuberculosis flare? Arthritis Rheum. 2008;58(1):327-328. |
| 11882. | Raychaudhuri S, Shmerling R, Ermann J, et al. Development of active tuberculosis following initiation of infliximab despite appropriate prophylaxis. Rheumatology (Oxford). 2007;46(5):887-888. |
| 11883. | Matsumoto T, Tanaka T, Kawase I. Infliximab for rheumatoid arthritis in a patient with tuberculosis. N Engl J Med. 2006;355(7):740-741. |
| 11884. | Lesnik A, Bolivar J, Morel J, Taourel P. Pseudotumoral colonic tuberculosis complicating rheumatoid arthritis treated with a tumor necrosis factor antagonist. AJR Am J Roentgenol. 2006;186(6):1799-1800. |
| 11885. | Imaizumi K, Sugishita M, Usui M, Kawabe T, Hashimoto N, Hasegawa Y. Pulmonary infectious complications associated with anti-TNFα therapy (infliximab) for rheumatoid arthritis. Intern Med . 2006;45(10):685-688. |
| 11886. | Rovere Querini P, Vecellio M, Sabbadini MG, et al. Miliary tuberculosis after biological therapy for rheumatoid arthritis. Rheumatology (Oxford). 2002;41(2):231. |
| 11887. | Cordero-Coma, Benito MF, Hernández AM, et al. Serpiginous Choroiditis. Ophthalmology. 2008;115(9):1633-1633.e1-2. |
| 11888. | Mancini G, Erario L, Gianfreda R, et al. Tuberculosis and Legionella pneumophila pneumonia in a patient receiving anti-tumour necrosis factor-α (anti-TNF-α) treatment. Eur Soc Clin Microbiol Infect Dis . 2007;13(10):1036-1037. |
| 11889. | Accorinti M, Pirraglia MP, Paroli MP, et al. Infliximab treatment for ocular and extraocular manifestations of Behçet’s disease. Jpn J Ophthalmol. 2007;51(3):191-196. |
| 11890. | van der Klooster JM, Bosman RJ, Oudemans-van Straaten HM, van der Spoel JI, Wester JP, Zandstra DF. Disseminated tuberculosis, pulmonary aspergillosis and cutaneous herpes simplex infection in a patient with infliximab and methotrexate. Intensive Care Med. 2003;29(12):2327-2329. |
| 11891. | Parra Ruiz J, Ortego Centeno N, Raya Alvarez E. Development of tuberculosis in a patient treated with infliximab who had received prophylactic therapy with isoniazid. J Rheumatol. 2003;30(7):1657-1658. |
| 11892. | Taylor JC, Orkin R, Lanham J. Tuberculosis following therapy with infliximab may be refractory to antibiotic therapy. Rheumatology (Oxford) . 2003;42(7):901-902. |
| 11893. | Uthman I, Kanj N, El-Sayad J, et al. Miliary tuberculosis after infliximab therapy in Lebanon. Clin Rheumatol . 2004;23(3):279-280. |
| 11894. | Armbrust W, Kamphuis SS, Wolfs TW, et al. Tuberculosis in a nine-year-old girl treated with infliximab for systemic juvenile idiopathic arthritis. Rheumatology (Oxford). 2004;43(4):527-529. |
| 11895. | Lim WS, Powell RJ, Johnston ID. Tuberculosis and treatment with infliximab. N Engl J Med. 2002;346(8):623-624. |
| 11954. | Wagner TE, Huseby ES, Huseby JS. Exacerbation of Mycobacterium tuberculosis enteritis masquerading as Crohn’s disease after treatment with a tumor necrosis factor-α inhibitor. Am J Med . 2002;112(1):67-69. |
| 11955. | Seong SS, Choi, CB, Woo JH, et al. Incidence of tuberculosis in Korean patients with rheumatoid arthritis (RA): effects of RA itself and of tumor necrosis factor blockers. J Rheumatol . 2007;34(4):706-711. |
| 12418. | Cooper J, Flückiger B, Traichl B, Diener PA, Otto P, von Kempis J. Abdominal pain in a patient with ankylosing spondylitis under treatment with infliximab. J Clin Rheumatol . 2009;15(5):244-246. |
| 12419. | Perlmutter A, Mittal A, Menter A. Tuberculosis and tumour necrosis factor-alpha inhibitor therapy: a report of three cases in patients with psoriasis. Comprehensive screening and therapeutic guidelines for clinicians. Br J Dermatol . 2009;160(1):8-15. |
| 12420. | Hirano Y, Kojima T, Kanayama Y, Ishikawa H, Ishiguro N. A case of lung tuberculosis in a patients with rheumatoid arthritis treated with infliximab after antituberculosis chemoprophylaxis with isoniazid. Mod Rheumatol. 2009;19(3):323-328. |
| 12421. | Dimakou K, Papaioannides D, Latsi P, et al. Disseminated tuberculosis complicating anti-TNF-α therapy. Int J Clin Pract . 2004;58(11):1052-1055. |
| 12422. | van der Kooij SM, le Cessie S, Goekoop-Ruiterman YP, et al. Clinical and radiological efficacy of initial vs delayed treatment with infliximab plus methotrexate in patients with early rheumatoid arthritis. Ann Rheum Dis. 2009;68(7):1153-1158. |
| 12447. | Sichletidis L, Settas L, Spyratos D, et al. Tuberculosis in patients receiving anti-TNF agents despite chemoprophylaxis. Int J Tuberc Lung Dis . 2006;10(10)1127-1132 |
| 12448. | Garcia Vidal C, Rodríguez Fernández S, Martínez Lacasa J, et al. Paradoxical response to antituberculous therapy in infliximab-treated patients with disseminated tuberculosis. Clin Infect Dis . 2005:40(5):756-759. |
| 12449. | Stas Ph, D’Hoore A, Van Assche G, et al. Miliary tuberculosis following infliximab therapy for Crohn disease: A case report and review of the literature. Acta Gastroenterol Belg . 2006;69(2): 217-220. |
| 12450. | Garcia-Vidal C, Rodríguez-Fernández S, Teijón S, et al. Risk factors for opportunistic infections in infliximab-treated patients: the importance of screening in prevention. Eur J Clin Microbiol Infect Dis. 2009;28(4):331-337. |
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Next Page: Infliximab and the Risk of Tuberculosis — Other Published Literature »
Prescribing Information and Medication Guide
REMICADE® (infliximab) Indications and Important Safety Information
INDICATIONS AND USAGE
Crohn’s Disease
REMICADE is indicated for reducing signs and symptoms and inducing and maintaining clinical remission in adult and pediatric patients with moderately to severely active Crohn’s disease who have had an inadequate response to conventional therapy.
REMICADE is indicated for reducing the number of draining enterocutaneous and rectovaginal fistulas and maintaining fistula closure in adult patients with fistulizing Crohn’s disease.
Ulcerative Colitis
REMICADE is indicated for reducing signs and symptoms, inducing and maintaining clinical remission and mucosal healing, and eliminating corticosteroid use in patients with moderately to severely active ulcerative colitis who have had an inadequate response to conventional therapy.
Rheumatoid Arthritis
REMICADE, in combination with methotrexate, is indicated for reducing signs and symptoms, inhibiting the progression of structural damage, and improving physical function in patients with moderately to severely active rheumatoid arthritis.
Ankylosing Spondylitis
REMICADE is indicated for reducing signs and symptoms in patients with active ankylosing spondylitis.
Psoriatic Arthritis
REMICADE is indicated for reducing signs and symptoms of active arthritis, inhibiting the progression of structural damage, and improving physical function in patients with psoriatic arthritis.
Plaque Psoriasis
REMICADE is indicated for the treatment of adult patients with chronic severe (i.e., extensive and /or disabling) plaque psoriasis who are candidates for systemic therapy and when other systemic therapies are medically less appropriate. REMICADE should only be administered to patients who will be closely monitored and have regular follow-up visits with a physician.
IMPORTANT SAFETY INFORMATION
RISK OF INFECTIONS
Patients treated with REMICADE® (infliximab) are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. Discontinue REMICADE® if a patient develops a serious infection or sepsis.
Reported infections include:
- Active tuberculosis (TB), including reactivation of latent TB. Patients frequently presented with disseminated or extrapulmonary disease. Patients should be tested for latent TB before and during treatment with REMICADE®. 1,2 Treatment for latent infection should be initiated prior to treatment with REMICADE®.
- Invasive fungal infections, including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, and pneumocystosis. Patients may present with disseminated, rather than localized, disease. Empiric anti-fungal therapy should be considered in patients at risk for invasive fungal infections who develop severe systemic illness.
- Bacterial, viral, and other infections due to opportunistic pathogens.
The risks and benefits of treatment with REMICADE® should be carefully considered prior to initiating therapy in patients with chronic or recurrent infection. Closely monitor patients for the development of signs and symptoms of infection during and after treatment with REMICADE®, including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy.
In clinical trials, other serious infections observed in patients treated with REMICADE® included pneumonia, cellulitis, abscess, and skin ulceration.
MALIGNANCIES
Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers, including REMICADE®. Approximately half of these cases were lymphomas, including Hodgkin's and non-Hodgkin's lymphoma. The other cases represented a variety of malignancies, including rare malignancies that are usually associated with immunosuppression and malignancies that are not usually observed in children and adolescents. The malignancies occurred after a median of 30 months after the first dose of therapy. Most of the patients were receiving concomitant immunosuppressants.
Postmarketing cases of hepatosplenic T-cell lymphoma, a rare type of T-cell lymphoma, have been reported in patients treated with TNF blockers including REMICADE®. These cases have had a very aggressive disease course and have been fatal. All reported REMICADE® cases have occurred in patients with Crohn’s disease or ulcerative colitis and the majority were in adolescent and young adult males. All of these patients had received treatment with azathioprine or 6-mercaptopurine concomitantly with REMICADE® at or prior to diagnosis. Carefully assess the risks and benefits of treatment with REMICADE®, especially in these patient types.
In clinical trials of all TNF inhibitors, more cases of lymphoma were observed compared with controls and the expected rate in the general population. However, patients with Crohn’s disease, rheumatoid arthritis, or plaque psoriasis may be at higher risk for developing lymphoma. In clinical trials of some TNF inhibitors, including REMICADE®, more cases of other malignancies were observed compared with controls. The rate of these malignancies among patients treated with REMICADE® was similar to that expected in the general population whereas the rate in control patients was lower than expected. Cases of acute and chronic leukemia have been reported with postmarketing TNF-blocker use. As the potential role of TNF inhibitors in the development of malignancies is not known, caution should be exercised when considering treatment of patients with a current or a past history of malignancy or other risk factors such as chronic obstructive pulmonary disease (COPD).
CONTRAINDICATIONS
REMICADE® is contraindicated in patients with moderate to severe (NYHA Class III/IV) congestive heart failure (CHF) at doses greater than 5 mg/kg. Higher mortality rates at the 10 mg/kg dose and higher rates of cardiovascular events at the 5 mg/kg dose have been observed in these patients. REMICADE® should be used with caution and only after consideration of other treatment options. Patients should be monitored closely. Discontinue REMICADE® if new or worsening CHF symptoms appear. REMICADE® should not be (re)administered to patients who have experienced a severe hypersensitivity reaction or to patients with hypersensitivity to murine proteins or other components of the product.
HEPATITIS B REACTIVATION
TNF inhibitors, including REMICADE®, have been associated with reactivation of hepatitis B virus (HBV) in patients who are chronic carriers. Some cases were fatal. Patients at risk for HBV infection should be evaluated for prior evidence of HBV infection before initiating REMICADE®. Exercise caution when prescribing REMICADE® for patients identified as carriers of HBV and monitor closely for active HBV infection during and following termination of therapy with REMICADE®. Discontinue REMICADE® in patients who develop HBV reactivation and initiate antiviral therapy with appropriate supportive treatment. Exercise caution when considering resumption of REMICADE® and monitor patients closely.
HEPATOTOXICITY
Severe hepatic reactions, including acute liver failure, jaundice, hepatitis, and cholestasis have been reported rarely in patients receiving REMICADE® postmarketing. Some cases were fatal or required liver transplant. Aminotransferase elevations were not noted prior to discovery of liver injury in many cases. Patients with symptoms or signs of liver dysfunction should be evaluated for evidence of liver injury. If jaundice and/or marked liver enzyme elevations (e.g., ≥ 5 times the upper limit of normal) develop, REMICADE® should be discontinued, and a thorough investigation of the abnormality should be undertaken.
HEMATOLOGIC EVENTS
Cases of leukopenia, neutropenia, thrombocytopenia, and pancytopenia (some fatal) have been reported. The causal relationship to REMICADE® therapy remains unclear. Exercise caution in patients who have ongoing or a history of significant hematologic abnormalities. Advise patients to seek immediate medical attention if they develop signs and symptoms of blood dyscrasias or infection. Consider discontinuation of REMICADE® in patients who develop significant hematologic abnormalities.
HYPERSENSITIVITY
REMICADE® has been associated with hypersensitivity reactions that differ in their time of onset. Acute urticaria, dyspnea, and hypotension have occurred in association with infusions of REMICADE®. Serious infusion reactions including anaphylaxis were infrequent. Medications for the treatment of hypersensitivity reactions should be available.
NEUROLOGIC EVENTS
TNF inhibitors, including REMICADE®, have been associated with rare cases of new or exacerbated symptoms of demyelinating disorders including multiple sclerosis, optic neuritis, and Guillain-Barré syndrome, seizure, and CNS manifestations of systemic vasculitis. Exercise caution when considering REMICADE® in all patients with these disorders. Consider discontinuation for significant CNS adverse reactions.
AUTOIMMUNITY
Treatment with REMICADE® may result in the formation of autoantibodies and, rarely, in development of a lupus-like syndrome. Discontinue treatment if symptoms of a lupus-like syndrome develop.
ADVERSE REACTIONS
In clinical trials, the most common REMICADE® adverse reactions occurring in >10% of patients included infections (e.g. upper respiratory, sinusitis, and pharyngitis), infusion-related reactions, headache, and abdominal pain.
USE WITH OTHER DRUGS
The concomitant use of a TNF blocker and anakinra was associated with a higher risk of serious infections, therefore the use of REMICADE® in combination with anakinra is not recommended. Live vaccines should not be given with REMICADE®. Bring pediatric Crohn's patients up to date with all vaccinations prior to initiating REMICADE®.
Please see full Prescribing Information and Medication Guide for REMICADE®. Provide the Medication Guide to your patients and encourage discussion.
References: 1. American Thoracic Society, Centers for Disease Control and Prevention. Targeted tuberculin testing and treatment of latent tuberculosis infection. Am J Respir Crit Care Med. 2000;161:S221–S247. 2. See latest Centers for Disease Control guidelines and recommendations for tuberculosis testing in immunocompromised patients.