Infliximab Neurologic Events in Postmarketing Reports
Neurologic events in patients treated with infliximab have been reported in postmarketing data. The information discussed in this section is taken from postmarketing data published in the medical literature. 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 case reports in this section should not be read to rule out the existence of other case reports of neurologic events, published or otherwise.
Cases of Neurologic Events With Infliximab
A search of available published literature yielded 43 cases regarding infliximab and neurologic adverse events. These published reports have been divided into 2 groups: general neurologic and those that represent cases of Guillain-Barré Syndrome (GBS). The 2 tables summarize the patient information including the underlying disease for which infliximab was being used, the clinical course, treatment, and outcomes of these adverse events in patients receiving infliximab therapy. 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 case reports in this section should not be read to rule out the existence of other case reports of neurological adverse events, published or otherwise.
Cases of General Neurologic Events in Patients Treated With Infliximab Therapy
Thirty-two cases of neurologic events (non-GBS) were identified in the literature in patients treated with infliximab. Of these, 20 patients received infliximab for rheumatoid arthritis, 7 patients for Crohn’s disease, 2 patients for plaque psoriasis, 1 patient for psoriatic arthritis, 1 patient for ankylosing spondylitis, and 1 for severe symmetric polyarthritis. Outcome data were reported in all but 2 cases. Complete resolution was reported in 12 cases, whereas 18 cases reported persistent signs or symptoms at follow-up. There were no reported fatalities attributable to these neurologic adverse events. These events are summarized in See Table :Cases of General Neurologic Events in Patients Treated With Infliximab Therapy.
| Age Gender Disease State (AS, CD, PsA, PsO, RA, UC) Disease Duration Publication | Dose of Infliximab/ Regimen Duration of Infliximab Therapy | Other Immunosuppressant Medication and Medical History | Presentation and Clinical Course | Diagnosis/Outcome(s) |
|---|---|---|---|---|
|
54-yr-old Male AS 10 yrs Paolazzi 200912556 |
5 mg/kg every 8 wks Approximately 14 mo |
Medication history not reported. Concomitant medication: Chronic anticoagulant therapy |
After 8 mo: Progressive weakness of left hand small intrinsic muscles After 11 mo: Right foot dorsiflexion weakness After 13 mo: Muscle weakness in right arm Presence of definite FMCB in left ulnar nerve, right radial nerve and right peroneal nerve |
Diagnosis of definite MMNCB Infliximab discontinued after 14 mo Muscle strength progressively improved and returned to normal, except for a mild residual left hand weakness. Nerve conduction studies demonstrated complete resolution of radial and peroneal nerves FMCB. |
|
68-yr-old Male CD 2 yrs Chan 201012557 |
OTH dose 3 infusions |
Medication history not reported. Concomitant medication: Pantoprazole |
During the 3rd infusion: Developed sudden-onset bilateral blurry vision with bilateral inferior field defects MRI of brain and orbits was normal Developed sudden-onset bilateral blurry vision with bilateral inferior field defects |
Signs and symptoms were consistent with anterior optic neuropathy Infliximab discontinued Treated with IV methylprednisolone At 5 mo follow-up, vision did not significantly improve and optical coherence tomography revealed retinal nerve fiber layer thinning. |
|
46-yr-old Male CD Disease Duration not reported Dubcenco 2006295 |
9 infusions |
History of: Steroids AZA MTX Concomitant medication: Budesonide |
After 9th
Progressive fatigue, numbness and weakness in right hand and foot leading to severe ascending weakness of the right leg and complete foot drop Elevated antinuclear antibody titer Patchy distal muscle denervation, consistent with a proximal demyelinating process |
Peripheral neuropathy with inflammatory demyelinating polyneuropathy Treated with IVIG Complete resolution reported at 6 mo follow-up |
|
35-yr-old Female CD Disease Duration not reported Enayati 2005335 |
2 infusions |
History of: Sulfasalazine 6-MP Corticosteroids Cyclosporine Concomitant medication not reported. (Familial history MS and UC) |
18 mo after 2nd infusion: Increased lower extremity weakness and difficulty with gait |
Findings reported as consistent with MS Unable to walk 18 mo post last dose infliximab and admitted to rehabilitation for physical therapy |
|
37-yr-old Female CD and AS Diagnosed in 1984 Freeman 200511949 |
Repeated infusions administered |
History of: 5-aminosalicylate (oral) Prednisone Sulfasalazine Budesonide Concomitant medication not reported. |
New onset headache Left-arm numbness Tingling, cramping and numbness in the lateral aspect of her left leg MRI: single white matter hyperintensity in right superior frontal lobe |
Infliximab discontinued Symptoms persisted and MRI unchanged 6 mo after episode |
|
50-yr-old Female CD Disease Duration not reported Mejico 2004343 |
Dosage and Duration not reported |
Not reported |
3 wks after last infusion: Vision loss and pain – both in left eye MRI with contrast revealed enhancement of retrobulbar portion of the optic nerve |
Demyelinating disorder Infliximab discontinued Visual function spontaneously improved within 6 wks back to pretreatment functionality |
|
45-yr-old Female CD 5 yrs Strong 2004351 |
7 infusions |
History of: AZA Mesalamine Corticosteroids Concomitant medication not reported. |
1 wk post 7th
Pain and blurred vision in the left eye Visual acuity Pain on orbit palpation, and upward gaze Full extraocular movements MRI reported as normal |
Retrobulbar optic neuritis Infliximab discontinued IV methylprednisolone followed by oral prednisone 3 mo later vision and optic nerve returned to normal, although residual left-sided headache remained |
|
19-yr-old Female Crohn’s ileocolitis Disease Duration not reported Thomas 2004354 |
3 infusions |
History of: AZA Corticosteroids Concomitant medication: AZA |
2 wks before 3rd
Numbness and tingling along the lateral aspect of right hip developed and spread to right leg, right shoulder, and forearm Mild right hand weakness and blurred vision in right eye MRI of head, cervical spine and thoracic spine revealed lesions in the left internal capsule and lower thoracic spine |
Symptomatic improvement was reported but no change on MRI was seen 8 wks later |
|
47-yr-old Female PsA Disease Duration not reported
|
Dosage not reported Duration not specifically reported |
History of: MTX Leflunomide Concomitant medication not reported. (Sister diagnosed with MS) |
Approximately 9 mo after initiation of therapy: Paresthesia on right side of face Bilateral decrease in visual acuity Progressive paraparesis, paresthesia right upper limb Left upper limb clumsiness MRI: White matter hyperintensities on
CSF positive for oligoclonal bands |
IVIG and methylprednisolone Improvement reported with residual partial visual impairment and upper left limb clumsiness Several mo later, developed truncal ataxia and upper limb clumsiness. New lesions visible on MRI |
|
34-yr-old Female Severe symmetric polyarthritis Diagnosed in 2001 Rodriquez- Escalara 2005282 |
4 infusions |
History of: Aurothiomalate Sulfasalazine MTX Cyclosporine Concomitant medication not reported. |
Post 4th
Progressive weakness of both hands and right foot Severe motor distal deficits without sensory loss |
Multifocal motor neuropathy with conduction block Infliximab discontinued Treated with IVIG Complete recovery was reported |
|
40-yr-old Male Severe plaque PsO Disease Duration not reported Eguren 200912558 |
5 mg/kg (0, 2, 6, and every 8 wks) 6 infusions |
Medication history and concomitant medication not reported. |
2 weeks after the 6th infusion: Asymmetric progressive weakness involving the left foot and right hand Electrodiagnostic studies were consistent with a motor, demyelinating and predominantly axonal degeneration |
Peripheral neuropathy Infliximab discontinued Treated with IVIG Clinical symptoms improved at 6 mo follow-up, although residual mild weakness of the left foot dorsiflexion remained |
|
47-yr-old Male Severe plaque PsO Disease Duration not reported Eguren 200912559 |
5 mg/kg (0, 2, 6, and every 8 wks) 4 infusions |
Medication history and concomitant medication not reported. |
2 wks after the 4th infusion: 2 weeks of progressive paresthesia involving both legs and slight weakness of left foot dorsiflexion Electrodiagnostic studies showed features of mild demyelination of the left peroneal, both sural and the right posterior tibial nerves, and reduced amplitude of the sural sensory nerve action potentials |
Peripheral neuropathy Infliximab discontinued Neurological symptoms improved spontaneously with time Asymptomatic 4 mo later |
|
60-yr-old Male RA 11 yrs Tektonidou 20079368 |
Duration not reported |
History of: MTX Oral steroids Cyclosporine Concomitant medication: MTX Prednisolone |
5 mo after initiation of treatment: Progressive upper and lower limb weakness After receiving next scheduled infliximab injection: Difficulty elevating right arm, gripping objects, and in fingers’ fine movements Inability to walk ESR C-reactive protein Brain MRI was reported normal |
EMG compatible with pure multifocal motor neuropathy with conduction block Infliximab discontinued Treated with IVIG Recovery of muscle strength reported |
|
56-yr-old Female RA 5 yrs Tektonidou 20079368 |
3 infusions |
History of: MTX Leflunomide Prednisolone Concomitant medication not reported. |
1 mo after the 3rd
Progressive ascending feet to knee numbness and paresthesia of both legs beginning 1 mo after the 3rd infusion Achilles reflexes absent Decreased sensation to light touch with stocking pattern |
EMG compatible with axonal sensory polyneuropathy Infliximab discontinued Treated with IVIG Complete recovery reported and EMG normal at 2 mo follow-up |
|
76-yr-old Female RA Disease Duration not reported Bidaguren 20078157 |
20 mo |
History of: MTX Concomitant medication not reported. |
20 months after initiation of treatment: Sudden loss of visual acuity in left eye, with alterations in yellow-blue colors perception (Farnsworth- Munsell test) MRI: multiple demyelinating injuries in subcortical and periventricular white matter |
Retrobulbar optical neuritis Infliximab discontinued Treated with methylprednisolone for 3 days Visual acuity returned to normal |
|
31-yr-old Female RA
Simsek 200711695 |
4 infusions |
History of: MTX Sulfasalazine Leflunomide Prednisolone Another anti-TNF Concomitant medication not reported. |
1 mo post 4th
Decreased brightness perception Pain triggered by ocular movement Defects in visual field in her left eye Brain MRI normal |
Optic neuritis Infliximab and antituberculosis prophylaxis discontinued Treated with steroid therapy Issue reportedly resolved at 12 mo |
|
50-yr-old Female RA Disease Duration not reported Jarand 2006294 (Cont. below) |
5 infusions |
Not reported |
2 wks post 5th dose: Diplopia Right foot drop, and left hand weakness and numbness Weakness in wrist and finger extensors, intrinsic hand muscles, left triceps, right tibialis anterior and posterior, and the extensor hallucis longus Right patellar and left triceps reflexes absent, but sensation was intact |
Demyelinating polyneuropathy with conduction block Treated with IVIG At 6 mo: Some improvement in strength reported Continued distal limb weakness Loss of ankle reflexes New onset of tremor and mild distal sensory feet abnormalities |
|
MRI: Small area of nonspecific EMG: demyelinating polyneuropathy with conduction block Sural nerve biopsy: mild axon loss high proportion of thinly myelinated fibers |
At 35 mo: “Substantial clinical gains” reported in motor strength and deep tendon reflexes MRI was unchanged | |||
|
85-yr-old Female RA 8 yrs Jarand 2006294 |
3 infusions |
Not reported |
2 wks post 3rd
Glove and stocking numbness and ataxia Inability to tandem walk Areflexia EMG: Distal low limb denervation Loss of sensory nerve action potential Mild declines in motor conduction velocities Loss of position sensibility in toes |
Infliximab discontinued Treated with IV corticosteroids At 9 mo follow-up: Improved sensation Mild electrophysiologic improvement Persistent ataxia |
|
68-yr-old Female RA Disease Duration not reported Jarand 2006294 |
18 mo |
Medication history not reported. Concomitant medication: Leflunomide Prednisone |
Following 18 mo of therapy: Bilateral paresthesia and pain in hands/feet Loss of sensation in hands and feet for cold, pin prick, and light touch Vibration and position sensibility preserved EMG reported as normal |
Small-fiber sensory neuropathy Treatment with gabapentin Symptomatic improvement reported over time |
|
66-yr-old Female RA 5 yrs Tanno 2006297 |
5 infusions |
History of: MTX Prednisone Concomitant medication: MTX Prednisone |
3 wks after 4th
Mild dysesthesia in left hand, resolved spontaneously after 7 days After 5thinfusion: Severe numbness on right side of face, right hand, left side of limbs and trunk Visual field loss Gait disturbance MRI revealed multiple demyelinating lesions in the spinal cord, some lesions enhanced with contrast |
Author reported “CNS demyelination induced by infliximab” Prednisone (initiated with gradual taper) At 12 wk follow-up evaluation: Decreased number of or enhanced lesions on MRI Normal visual fields Little sensory disturbances No ataxic gait |
|
40-yr-old Female RA 10 yrs Cocito 20059367 |
14 mos |
Not reported |
Approximately 10 mo post initiation of treatment: Asymmetric progressive weakness of right forearm flexion and of intrinsic muscles of right hand Severe weakness of right biceps, right extensor carpi brachialis and right hand extensors No detectable sensory loss reported EMG: Nerve conduction block IgM |
Multifocal motor neuropathy Infliximab discontinued Treated with IVIG “Marked increase” in muscle strength was reported EMG: reduction of the number of nerve blocks |
|
41-yr-old Female RA 18 yrs Richette 20049366 |
6 infusions |
History of: Sulfasalazine MTX Cyclosporine Prednisolone Concomitant medication: MTX |
Post 6th dose: Dysesthesia in left peroneal nerve Hypesthesia in anterolateral part of left leg EMG compatible with mononeuritis of left peroneal nerve Muscle biopsy consistent with peripheral neuropathy secondary to necrotizing vasculitis |
Mononeuritis of left peroneal nerve IV methylprednisolone for 3 days followed by oral prednisone for 30 days Neurologic exam at 4 mo reported as normal. Patient did not report paresthesia |
|
48-yr-old Female RA 5 yrs Richette 20049366 |
Dosage and Duration not reported |
History of: Sulfasalazine MTX Hydroxychloroquine Methylprednisolone Cyclophosphamide Concomitant medication: Prednisone Leflunomide (History of neuronal necrotizing vasculitis of right leg. Diagnosed with sensory mononeuritis multiplex treated with methylprednisolone and cyclophos- phamide) |
8 hrs post 1stinfusion: Paresthesia of left leg Reoccurrence of hypesthesia in right leg |
Infliximab discontinued 3 doses of cyclophosphamide and prednisone dose increased Slight improvements in sensory neuropathy reported at 3 mo follow-up |
|
52-yr-old Male RA 5 yr history of seropositive, nodular RA Jarrett 20039365 |
7 infusions, discontinued after 10 mo |
History of: Sulfasalazine MTX Hydroxychloroquine Prednisone Concomitant medication: MTX |
12 wks after discontinuation: Acute onset of weakness of left knee extension |
Mononeuritis IV methylprednisolone Cyclophosphamide Complete recovery of limb function |
|
45-yr-old Male RA 14 yr history of seropositive RA Jarrett 20039365 |
1 infusion |
History of: Sulfasalazine MTX Hydroxychloroquine Concomitant medication: Leflunomide |
4th day after 1stinfusion: Patient reported progressive speech clumsiness over a Staccato speech on exam MRI showed areas of ischemia in the posterior putamen CSF negative for oligoclonal bands Visual evoked potentials normal |
Cerebral ischemia, probably vascular etiology Discontinued infliximab Leflunomide unchanged Spontaneous recovery reported |
|
54-yr-old Male RA Disease Duration not reported ten Tusscher 200311696 |
3 infusions |
Medication history not reported. Concomitant mediation: Leflunomide Prednisone Naproxen |
34 days post 3rd
Blurred vision
Severe disc swelling and visual fields defects |
Bilateral anterior optic neuritis Treated with steroids No recovery reported |
|
62-yr-old Female RA Disease Duration not reported ten Tusscher 200311696 |
4 infusions |
Medication history not reported. Concomitant mediation: Rofecoxib Salicylic acid |
40 days post 3rd infusion: Blurred vision Left eye showed signs consistent with optic nerve inflammation Similar symptoms and
signs in right eye after 4th
|
Bilateral anterior optic neuritis Treated with steroids No recovery reported |
|
54-yr-old Male RA Disease Duration not reported ten Tusscher 200311696 |
3 infusions |
Medication history not reported. Concomitant mediation: Prednisone Diclofenac |
14 days post 3rd
Loss of visual field in right eye 2 wks after receiving a 3rd dose of infliximab Exam #1: Bilateral optic disc swelling Capillary dilation Vascular leakage in optic nerve heads Subsequent loss of vision in left eye Exam #2:
Central visual field defect |
Bilateral anterior optic neuritis Treated with steroids No recovery reported |
|
55-yr-old Female RA 2 yrs Foroozan 2002337 |
9 infusions |
History of: MTX Concomitant medication: MTX |
3 days post 9th infusion: Loss of vision and ocular pain MRI (Gd): mild enhancement of orbital portion of left optical nerve |
Retrobulbar optic neuritis Corticosteroids, discontinuation of infliximab with reported improved vision with resolution of visual field defect |
|
53-yr-old Female RA Disease duration not reported Mohan 2001285 |
Dosage not reported 2.5 mo |
Not reported |
Diplopia, nystagmus, weakness, neurogenic bladder, paresthesia MRI findings of demyelination in tectum and spinal cord |
Demyelination Methylprednisolone and IVIG reportedly resulted in partial resolution |
|
42-yr-old Male RA Disease duration not reported Mohan 2001285 |
Dosage not reported 1 infusion |
Medication history not reported. Concomitant medication: Leflunomide Prednisolone |
Dysarthria MRI finding of demyelination |
Demyelination Treatment not reported |
|
6-MP=6-mercaptopurine; AS=ankylosing spondylitis; AZA=azathioprine; CD=Crohn’s disease; CSF=cerebrospinal fluid; EMG/ND=electromyogram/nerve conduction; ESR=erthrocyte sedimentation rate; FMCB= focal motor conduction blocks; hrs=hour(s); IVIG=IV immunoglobulin; MMNCB= multifocal motor neuropathy with conduction blocks; mo=month(s); MRI=magnetic resonance imaging; MRI (Gd)=gadolinium-enhanced magnetic resonance imaging; MTX=methotrexate; MS=multiple sclerosis; NSAID=nonsteroidal anti-inflammatory drug; PsA=psoriatic arthritis; PsO=psoriasis; RA=rheumatoid arthritis; UC=ulcerative colitis; wks=weeks; yr=year. | ||||
Case Reports of Guillain-Barré Syndrome in Patients Treated With Infliximab Therapy
In addition to the neurologic events reported in See Table :Cases of General Neurologic Events in Patients Treated With Infliximab Therapy, 11 cases of GBS were identified in the literature in patients treated with infliximab. These events are summarized in See Table :Cases of General Neurologic Events in Patients Treated With Infliximab Therapy. Of these 11 cases, 9 were reported in a publication by Shin, et al., 11333 that described a review of the FDA’s Adverse Event Reporting System database that was conducted to identify reports of GBS and Miller-Fisher Syndrome in patients administered tumor necrosis factor-α antagonist therapy. This review of the FDA’s postmarketing database identified 9 patients that developed GBS following infliximab therapy, including 1 patient that was reported previously in the medical literature.291 Outcome data were reported in all but 1 case. Complete resolution was reported in 2 cases, whereas 8 cases reported persistent signs or symptoms at follow-up. There were no reported fatalities attributable to these neurologic adverse events.
| Age Gender Disease State (AS, CD, PsA, PsO, RA, UC) Publication | Duration of Infliximab Therapy | Clinical Signs and Symptoms | Antecedent Events | EMG/NC | Therapy | Outcome(s) |
|---|---|---|---|---|---|---|
|
41-yr-old Female CD Shin 200611333 |
2 infusions |
Acute neuromuscular weakness Preexisting myotonic dystrophy |
Not reported |
Demyelinating polyneuropathy |
Not reported |
Partial resolution; positive re-challenge |
|
49-yr-old Female CD Shin 200611333 |
2 infusions |
Weakness Respiratory distress |
Low-grade fever of short duration |
Acute demyelinating polyneuropathy |
IVIG |
Not reported |
|
43-yr-old Male PsA Shin 200611333 |
5 infusions |
Ascending progressive quadriparesis Urinary retention |
Not reported |
Acute demyelinating polyneuropathy |
Not reported |
Partial resolution at 2 wks |
|
34-yr-old Male PsA Cisternas 2002291 Shin 200611333 |
2 infusions |
Ascending paralysis |
URI; MFS 14 yrs earlier |
Demyelinating polyradiculoneuropathy |
Mechanical ventilation IVIG |
Complete resolution at 3 wks; negative re-challenge at 1 mo |
|
56-yr-old Male RA Shin 200611333 |
12 infusions |
Ataxia Dysarthria progressing to areflexic quadriplegia |
Flu vaccine |
Demyelinating polyneuropathy with proximal conduction defect |
IVIG Methylpred- nisolone |
Partial resolution at 3.5 mo; positive re-challenge with subsequent 3 infusions |
|
66-yr-old Female RA Shin 200611333 |
6 infusions |
Progressive weakness and imbalance |
Not reported |
Not reported |
IVIG |
No response to therapy |
|
56-yr-old Female RA Shin 200611333 |
4 infusions |
Symmetric quadriparesis |
URI |
Axonal polyneuropathy |
IVIG |
Partial resolution at 2 wks |
|
62-yr-old Male RA Shin 200611333 |
4 infusions |
Progressive ascending paralysis Paraesthesia of legs Inability to walk |
Fever of unknown origin |
Not reported |
IVIG Plasmaphe- resis Mechanical ventilation |
Partial resolution at 10 mo |
|
81-yr-old Female RA Shin 200611333 |
4 infusions |
Weakness Paresthesia Decreased diaphragmatic function |
Not reported |
Normal at |
IVIG Plasmaphe- resis |
Relapse off-drug; partial resolution |
|
46-yr-old Female RA Silburn 20089764 |
3 infusions |
Paresthesia and weakness of hands and lower limbs Muted plantar responses Reduced knee and ankle reflexes Cough and malaise for 10 days prior to event CSF protein level |
Not reported |
Segmental demyelinating polyneuropathy consistent with GBS |
Not reported |
Spontaneous improvement reported |
|
47-yr-old Female UC Bouchra 200911956 |
3 infusions |
2 wks after the third infusion: Paresthesia in hands and lower limbs Decreased strength in lower limbs Decreased knee and ankle reflexes Muted plantar responses |
Not reported |
EMG consistent with Guillain-Barré |
Treatment with IV corticoste roids was ineffective Treated with IVIG |
Complete recovery reported within a few wks Follow-up EMG was reported as normal |
|
AS=ankylosing spondylitis; CD=Crohn’s disease; CSF=cerebrospinal fluid; EMG/NC=electromyogram/nerve conduction; IVIG=intravenous immunoglobulin; MFS=Miller-Fisher syndrome; mo=month(s); PsA=psoriatic arthritis; PsO=psoriasis; RA=rheumatoid arthritis; TNF=tumor necrosis factor; UC=ulcerative colitis; URI=upper respiratory tract infection; wks=weeks; yr=year(s). | ||||||
Content on this page was last reviewed on January 31, 2010.
Content on this page was last changed on April 01, 2010.
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| 335. | Enayati PJ, Papadakis KA. Association of anti-tumor necrosis factor therapy with the development of multiple sclerosis. J Clin Gastroenterol . 2005;39(4):303-306. |
| 337. | Foroozan R, Buono LM, Sergott RC, Savino PJ. Retrobulbar optic neuritis associated with infliximab. Arch Ophthalmol. 2002;120(7):985-987. |
| 343. | Mejico LJ. Infliximab-associated retrobulbar optic neuritis. Arch Ophthalmol. 2004;122(5):793-794. |
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| 9365. | Jarrett SJ, Cunnane G, Conaghan PG, et al. Anti-tumor tecrosis tactor-alpha therapy-induced vasculitis: case series. J Rheumatol. 2003;30(10):2287-2291. |
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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.