Treatment of CNS sarcoidosis with infliximab and mycophenolate mofetil

Abstract

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

A Concise Review of Pulmonary Sarcoidosis

“…Neurologic disease can also be refractory to conventional treatments. Again, infliximab has been reported as successful in treating patients with neurosarcoidosis who have failed other therapies (100,101). A recent post hoc analysis of a trial of infliximab for pulmonary sarcoidosis found that an elevated C-reactive protein was associated with significantly better response to treatment (102).…”

Renal Transplantation in Patients with Sarcoidosis

“…Steroids have been effectively used as a first-line therapy for sarcoidosis, first relapse, or renal graft recurrence (5,10,26 -30). Also, mycophenolate mofetil has been used as steroid-sparing agent in cases of steroid-dependent sarcoidosis (37)(38)(39)(40)(41). Sarcoidosis is associated with an increase in peripheral regulatory T lymphocytes (Treg) cells, accounting for the anergic state usually observed in these patients; however, these levels are still unable to control local inflammation and granuloma formation (42).…”

Sarcoidosis: Unknown Etiology and Genetic Predisposition Provides Therapeutic Challenges

“…These drugs ultimately block RNA and DNA synthesis while inducing cell cycle arrest [105]. Mycophenolate is not commonly implemented; however, in small trials it has shown effectiveness in treating cutaneous, ocular and neurological sarcoidosis [114][115][116].…”