The study, “Successful therapy with rituximab in three patients with probable neurosarcoidosis,” was published in the journal Therapeutic Advances in Neurological Disorders.
Neurosarcoidosis — the development of sarcoidosis’ hallmark immune cell clumps, called granulomas, in the nervous system — occurs in about 5-15% of sarcoidosis patients. The risk of bleeding and neurological deterioration with biopsy means that diagnosis is often done by combining clinical presentation, imaging, and laboratory work-up.
Corticosteroids are commonly used as first-line therapy, but in severe and recurrent cases, immunomodulating or cytotoxic treatments such as azathioprine, methotrexate and cyclophosphamide are used as stand-alone treatments or combined with corticosteroids.
German researchers presented three cases of patients with clinical and histological proof of sarcoidosis and a probable diagnosis of neurosarcoidosis. None responded to first-line therapy with corticosteroids or to alternative treatment regimens.
Case 1 was a 51-year-old woman with a history of pulmonary sarcoidosis and a syringomyelia – a fluid-filled cyst within the spinal cord. In 2012 she presented with dizziness, headache, left thigh hypoesthesia — a reduced sense of touch or sensation — and progressive fatigue. She was treated with a combination of azathioprine 100 mg/day and methotrexate 5 mg/week.
The patient then revealed several T2-hyperintense lesions on magnetic resonance imaging (MRI), located close to the left and right ventricles, which are interconnected brain cavities filled with a liquid called cerebrospinal fluid. Given the suspicion of central nervous system (CNS) involvement, her treatment regimen was changed to azathioprine 100 mg/day and Remicade (5 mg/kg body weight), which led to clinical and radiological stability over two years.
However, a severe increase in enzymes called serum transaminases — a possible indication of liver injury — forced treatment discontinuation in 2014. After normalization of enzyme levels, the treatment was altered to Remicade 5 mg/kg body weight every four weeks and dimethyl fumarate — used in patients with psoriasis and multiple sclerosis — at 5 mg/kg body weight, but recurrent infections led to another treatment discontinuation.
The patient then started taking Genentech’s Rituxan, which halted disease progression and significantly lessened fatigue. Up to the last visit, in September 2017, the patient had received 500 mg of Rituxan three times. She showed clinical stability, no evidence of disease progression, and no recurrent infections.
Case 2 was a 50-year-old woman with sarcoidosis that mimicked vasculitis (a blood vessel inflammation), who presented in 2011 with sensory disturbances of both legs. She showed a mild gait disturbance upon neurological examination.
The patient was being treated with corticosteroids (60 mg/day). She showed a spinal cord lesion in the cervical and thoracic cord on MRI. Diagnosis of neurosarcoidosis was then considered, leading to treatment with Remicade 5 mg/kg body weight every four weeks. The patient subsequently showed gradual clinical improvement until an almost complete remission after eight treatment cycles.
But for reasons not known, she did not continue the treatment with Remicade. A few weeks later, the patient developed the same gait disturbances she had experienced before. Immunosuppression with azathioprine (200 mg/day) had no benefit, with the patient reporting progressive sensory disturbances in both legs, followed by hypoesthesia and gait ataxia — lack of muscle coordination — upon neurological examination. She was unable to walk more than 500 meters without rest.
Treatment with azathioprine was interrupted and Remicade was resumed, again providing a significant neurological improvement. However, the woman showed serum anti-Remicade antibodies at the 13th infusion and a low serum concentration of the therapy (0.1 µg/ml or lower), which led to switching immunomodulating therapy to Rituxan, followed by maintenance Rituxan infusions (500 mg) every six to nine months. This regimen enabled continuous neurological stability.
Similar to Case 1, this woman had received Rituxan 500 mg three times by the time of her last visit, in October 2017. She demonstrated no neurological deficits and reported being well, with no adverse events.
Case 3 was a 57-year-old man with a history of pulmonary sarcoidosis. He presented in March 2012 with a residual left facial paralysis and a right hemiparesis — slight paralysis or weakness — after experiencing a left middle cerebral artery stroke two months earlier.
The man’s medication included azathioprine 100 mg/day at hospital admission. He demonstrated a T2 lesion in the brain’s left parietal lobe, narrowing in the distal part of the middle cerebral artery and multiple blood vessel obstructions in the affected brain area, which the clinicians considered highly consistent with vasculitis associated with neurosarcoidosis.
Remicade 5 mg/kg body weight every four weeks was then added to his regimen. The patient also took 100 mgs of aspirin a day. He subsequently developed several adverse events, including fever, fatigue, hip bone pain and ischemic strokes. As a result, azathioprine was replaced by cyclophosphamide (cumulative dose 670 mg/m2), providing neuroradiological stability over a year.
However, a progressive third nerve palsy was reported in November 2013. Treatment with Rituxan was initiated, leading to clinical improvement. The man was receiving Rituxan at 250-500 mg every six months by the time of the study’s end. He had no further ischemic strokes and was progression-free at the last visit.
Noting the existence of only two prior case reports describing successful treatment of refractory neurosarcoidosis with Rituxan — which depletes circulating CD20+ immune B-cells — the scientists considered that the findings “support the hypothesis that rituximab (Rituxan) is beneficial and well- tolerated” in this patient population.
“We propose that B-cell-directed therapies may become an attractive option,” they said, cautioning that controlled studies are needed to validate the efficacy and safety of Rituxan in these patients.