Infliximab for the treatment of CNS sarcoidosis: A multi-institutional series

Abstract

Objective: To describe clinical and imaging responses in neurosarcoidosis to infliximab, a monoclonal antibody against tumor necrosis factor-α.

Methods: Investigators at 6 US centers retrospectively identified patients with CNS sarcoidosis treated with infliximab, including only patients with definite or probable neurosarcoidosis following rigorous exclusion of other causes.

Results: Of 66 patients with CNS sarcoidosis (27 definite, 39 probable) treated with infliximab for a median of 1.5 years, the mean age was 47.5 years at infliximab initiation (SD 11.7, range 24-71 years); 56.1% were female; 62.1% were white, 37.0% African American, and 3% Hispanic. Sarcoidosis was isolated to the CNS in 19.7%. Using infliximab doses ranging from 3 to 7 mg/kg every 4-8 weeks, MRI evidence of a favorable treatment response was observed in 82.1% of patients with imaging follow-up (n = 56), with complete remission of active disease in 51.8% and partial MRI improvement in 30.1%; MRI worsened in 1 patient (1.8%). There was clinical improvement in 77.3% of patients, with complete neurologic recovery in 28.8%, partial improvement in 48.5%, clinical stability in 18.2%, worsening in 3%, and 1 lost to follow-up. In 16 patients in remission when infliximab was discontinued, the disease recurred in 9 (56%), typically in the same neuroanatomic location.

Conclusions: Most patients with CNS sarcoidosis treated with infliximab exhibit favorable imaging and clinical treatment responses, including some previously refractory to other immunosuppressive treatments.

Classification of evidence: This study provides Class IV evidence that for patients with CNS sarcoidosis infliximab is associated with favorable imaging and clinical responses.

Figure 1. Progression of CNS sarcoidosis over 10 years despite conventional immunosuppressive therapy with complete remission on infliximab

At age 37, this previously healthy African American man developed bilateral sequential optic neuropathy. Over the next 3 years, he progressed to blindness with no light perception bilaterally, despite aggressive glucocorticoid therapy. Chest CT at age 39 showed mild bilateral hilar lymphadenopathy, and biopsy of nasal mucosa at age 42 was consistent with sarcoidosis. Over the next decade, he went on to develop hypopituitarism, cognitive impairment (correlating with further subcortical involvement on neuroimaging), and intractable hiccups despite treatment with oral glucocorticoids and azathioprine. At age 50, brain biopsy of an enhancing lesion in the right thalamus showed non-necrotizing granulomatous inflammation consistent with CNS sarcoidosis. The top and bottom rows show serial T1 postgadolinium MRIs from 2 different anatomic levels with the x-axis aligned by time. The MRIs show that there is persistent waxing and waning abnormal nodular enhancement (arrows show some examples) in the same neuroanatomic distribution over 10 years, which finally remitted following treatment with infliximab, initially at an escalated dose of 7 mg/kg IV every 6 weeks and since maintained on infliximab 5 mg/kg Q8 weeks together with azathioprine 50 mg/d and replacement doses of glucocorticoids. Remission of the CNS process has been maintained for over 4 years. The patient had breakthrough sarcoidal granulomatous dermatitis on this maintenance regimen 2.5 years into his CNS remission, and the facial lesions subsequently resolved. His hiccups resolved and cognition returned to baseline; as expected, there has been no improvement in visual function. ACE = angiotensin-converting enzyme; IgG = immunoglobulin G; OCB = oligoclonal band; WBC = white blood cell.

Figure 2. Improvement of leptomeningeal, pituitary/hypothalamic, and optic chiasm involvement of neurosarcoidosis following infliximab and worsening upon infliximab discontinuation

A 32-year-old white man with definite neurosarcoidosis proven by biopsy of a hypothalamic lesion progressed despite treatment with glucocorticoids, azathioprine, and methotrexate. (A) Coronal and midsagittal T1-weighted MRI brain with gadolinium contrast obtained after treatment with the aforementioned for 2 years demonstrated significant, progressing nodular leptomeningeal enhancement along the interhemispheric fissure (small arrow), surrounding the optic chiasm and pituitary stalk (large arrow), and brainstem (arrowhead) including the cerebellopontine angle and upper cervical spinal cord. (B) Coronal and midsagittal T1-weighted MRI brain with gadolinium contrast after 2 months of infliximab demonstrated near-complete resolution of previously active disease with only a small amount of possible enhancement along the optic chiasm (arrowhead). The patient was maintained in remission while on infliximab for 5 years. (C) Upon cessation of infliximab, the patient had recurrence of disease within 8 months. Coronal and midsagittal T1-weighted MRI brain with gadolinium contrast demonstrated nodular leptomeningeal enhancement at previous sites of active disease including the optic chiasm (arrow) and medullopontine angle (arrowhead). He was retreated with infliximab with clinical improvement.