Tumour necrosis factor   inhibitor treatment for sarcoidosis refractory to conventional treatments: a report of five patients

Pritchard, Charles; K, Nadarajah

doi:10.1136/ard.2002.004226

Cited by 103 publications

(54 citation statements)

References 12 publications

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“…[6][7][8][9] We found that combination therapy with infliximab and MMF ameliorated CNS complications of sarcoidosis that had previously flared during a corticosteroid taper, irrespective of the site (cerebral hemispheres vs spinal cord; leptomeningeal vs extradural vs parenchymal) or distribution (solitary vs multifocal) of lesions. Patients universally experienced symptomatic improvement by the fourth infusion of infliximab that was sustained throughout a 24-to 39-month follow-up period.…”

Section: Discussionmentioning

confidence: 74%

Treatment of CNS sarcoidosis with infliximab and mycophenolate mofetil

Moravan¹,

Segal²

2009

Neurology

134

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Objective: To describe the effects of the anti-tumor necrosis factor neutralizing antibody, infliximab, and the antiproliferative immunosuppressant, mycophenolate mofetil, in refractory neurosarcoidosis. Methods:We treated patients with biopsy-proven sarcoidosis and CNS involvement, who had failed treatment with steroids, with infliximab (5 mg/kg on weeks 0, 2, and 6, and then every 6 -8 weeks thereafter). Six out of seven patients were co-treated with mycophenolate mofetil (1,000 mg PO BID). Patients underwent a review of symptoms and complete neurologic examination every 3 months and MRI scanning before and after 3-4 infusions of infliximab.Results: All patients reported significant symptomatic improvement by the fourth infusion of infliximab, including relief of headache and neuropathic pain, reversal of motor, sensory, or coordination deficits, and control of seizure activity. Furthermore, infliximab therapy was universally associated with a decrease in lesion size or suppression of gadolinium enhancement as documented by MRI. A positive treatment response was attained irrespective of location or distribution of CNS involvement by sarcoidosis (dural/leptomeningeal based vs intraparenchymal; cord vs brain; single lesion vs multifocal). There were no serious adverse effects in a follow-up period spanning 6 -18 months. Conclusions:Combination treatment with mycophenolate mofetil and infliximab is a promising therapeutic approach for neurosarcoidosis. Neurology GLOSSARYA ϭ azathioprine; AA ϭ African American; Cy ϭ cyclophosphamide; E ϭ etanercept; EDSS ϭ Expanded Disability Status Scale; MMF ϭ mycophenolate mofetil; MMSE ϭ Mini-Mental State Examination; N ϭ neurologic; O ϭ ophthalmologic; P ϭ pulmonary; Pq ϭ Plaquenil; R ϭ rheumatologic; Si ϭ sinuses; S ϭ steroids; TNF ϭ tumor necrosis factor; VPS ϭ ventriculoperitoneal shunt; W ϭ white.CNS infiltration occurs in approximately 5% of patients with sarcoidosis; it is associated with a less favorable course and accounts for a disproportionate amount of disability.1 Neurosarcoidosis is often difficult to manage. In one of the larger clinical series, over 70% of patients relapsed or progressed despite treatment with corticosteroids and oral immunosuppressant agents.2 Since neurosarcoidosis tends to flare in the midst of prednisone tapers, those afflicted are often subject to the complications of chronic corticosteroid usage. Hence, there is a clear need for novel therapeutic strategies in this disorder.It has been speculated that tumor necrosis factor (TNF)␣ neutralizing agents might be effective in sarcoidosis based on animal studies demonstrating a critical role of TNF␣ in granulomatous inflammation and an association between TNF␣ expression in alveolar macrophages and active pulmonary sarcoidosis. 3,4 Infliximab is a chimeric monoclonal humanmurine IgG antibody directed against TNF␣ approved for the treatment of rheumatoid

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Section: Discussionmentioning

confidence: 74%

Treatment of CNS sarcoidosis with infliximab and mycophenolate mofetil

Moravan¹,

Segal²

2009

Neurology

134

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“…Several case reports suggest that infliximab, a tumor necrosis-a inhibitor, is useful in cases of spinal cord sarcoidosis refractory to more conservative management (Pritchard and Nadarajah, 2004;Sollberger et al, 2004;Saleh et al, 2006;Santos et al, 2010). Given the extreme rarity of spinal cord sarcoidosis, its overall dismal prognosis with traditional management, and the impressive results reported with infliximab, clinicians should be aware of its potential application to this often disabling disease and consider early treatment.…”

Section: Sarcoidosismentioning

confidence: 99%

Acute inflammatory myelopathies

Cree

2014

Handbook of Clinical Neurology

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“…[83][84][85][86][87][88][89][90] Table 7 summarizes the use of infl iximab for lung disease, including four RCTs for lung disease 86,89,91,92 and 11 case series of infl iximab in which additional information regarding toxicity is provided. 85,[93][94][95][96][97][98][99][100][101][102] Also included in Table 8 are several studies in nonpulmonary disease that provide specifi c information regarding toxicity of the drug. 10,76, 3.1.3.1 Toxicity-Detailed reviews of the side effect profi le have been published.…”

Section: Infl Iximabmentioning

confidence: 99%

Monitoring of Nonsteroidal Immunosuppressive Drugs in Patients With Lung Disease and Lung Transplant Recipients

Baughman

Meyer

Nathanson

et al. 2012

Chest

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Objectives: Immunosuppressive pharmacologic agents prescribed to patients with diffuse interstitial and infl ammatory lung disease and lung transplant recipients are associated with potential risks for adverse reactions. Strategies for minimizing such risks include administering these drugs according to established, safe protocols; monitoring to detect manifestations of toxicity; and patient education. Hence, an evidence-based guideline for physicians can improve safety and optimize the likelihood of a successful outcome. To maximize the likelihood that these agents will be used safely, the American College of Chest Physicians established a committee to examine the clinical evidence for the administration and monitoring of immunosuppressive drugs (with the exception of corticosteroids) to identify associated toxicities associated with each drug and appropriate protocols for monitoring these agents. Methods: Committee members developed and refi ned a series of questions about toxicities of immunosuppressives and current approaches to administration and monitoring. A systematic review was carried out by the American College of Chest Physicians. Committee members were supplied with this information and created this evidence-based guideline. Conclusions: It is hoped that these guidelines will improve patient safety when immunosuppressive drugs are given to lung transplant recipients and to patients with diffuse interstitial lung disease. CHEST 2012; 142(5):e1S-e111SAbbreviations: ACCP 5 American College of Chest Physicians; ALT 5 alanine aminotransferase; ATG 5 antithymocyte globulin; CHF 5 congestive heart failure; CMV 5 cytomegalovirus; CNI 5 calcineurin inhibitor; COI 5 confl ict of interest; CsA 5 cyclosporin A; FDA 5 US Food and Drug Administration; HBV 5 hepatitis B virus; HMG-CoA 5 b -hydroxy-bmethylglutaryl-coenzyme A; HSP 5 Health and Science Policy Committee; IL2RA 5 IL-2 receptor a ; ILD 5 interstitial lung disease; IPF 5 idiopathic pulmonary fi brosis; ITP 5 idiopathic thrombocytopenia purpura; LAM 5 lymphangioleiomyomatosis; MESNA 5 sodium 2-sulfonylethanesufonate; MPA 5 mycophenolic acid; mTOR 5 mammalian target of rapamycin; PTLD 5 posttransplant lymphoproliferative disease; RCT 5 randomized controlled trial; SIRS 5 systemic infl ammatory response syndrome; TNF 5 tumor necrosis factor; TPMT 5 thiopurine methyltransferase

show abstract

Tumour necrosis factor inhibitor treatment for sarcoidosis refractory to conventional treatments: a report of five patients

Cited by 103 publications

References 12 publications

Treatment of CNS sarcoidosis with infliximab and mycophenolate mofetil

Treatment of CNS sarcoidosis with infliximab and mycophenolate mofetil

Acute inflammatory myelopathies

Monitoring of Nonsteroidal Immunosuppressive Drugs in Patients With Lung Disease and Lung Transplant Recipients

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