Infliximab and Its Biosimilars Hold Both Promise and Challenges in Treating Neurosarcoidosis

Sarcoidosis is a systemic disease of undetermined etiology that results in the formation of granulomas. In neurosarcoidosis, a potentially life-threatening manifestation of sarcoidosis that accounts for up to 15% of cases of sarcoidosis, the central and peripheral nervous system may be affected, leading to symptoms such as seizures, meningitis, or optical nerve involvement.¹ Corticosteroids are often given as therapy for neurosarcoidosis, but there remains a need for more effective treatment, and infliximab is increasingly used in this context.

Biosimilar Infliximab in Neurosarcoidosis

A recent study, published in the Journal of Neurology, reported on a retrospective study, conducted at a single center in France, that investigated the safety and efficacy of biosimilar infliximab in treating patients with neurosarcoidosis.²

In total, 20 patients with histologically documented neurosarcoidosis were treated with an infliximab biosimilar, with 12 patients starting treatment with the biosimilar and 8 switching from the reference infliximab. In total, 18 patients received corticosteroids together with infliximab, and 16 received either methotrexate or azathioprine together with infliximab.

The investigators found that, in a follow-up period with a median duration of 25 months (range, 19-28), 6 patients experienced a relapse. The relapse rates and time to relapse did not differ between the patients who started with the biosimilar versus those who switched treatment. In total, 9 patients experienced 11 adverse events (AEs) while treated with the biosimilar. These included 5 infections, 4 cases of urticaria, and 1 case each of headache and diarrhea. All of the AEs were of grade 2 or less.

Treating neurosarcoidosis with biosimilar infliximab, say the authors, was both safe and efficacious.

Neurosarcoidosis as an Immune Checkpoint—Related AE

Having infliximab and its biosimilars available as treatment options for patients with neurosarcoidosis may prove to be helpful as more patients with cancer undergo immune checkpoint inhibitor therapy that can lead to immune-related AEs that include neurosarcoidosis.

As a recent case study in the Journal for ImmunoTherapy of Cancer reported, neurosarcoidosis may appear up to 1 year after discontinuation of immune checkpoint therapy.³ The case study describes a patient who received ipilimumab and nivolumab for recurrent metastatic melanoma and developed systemic sarcoidosis shortly after starting treatment. Immune checkpoint therapy was discontinued, and approximately 1 year later, the patient was found to have neurosarcoidosis.

The patient received treatment with steroids, infliximab, and later methotrexate, and achieved clinical and radiographic improvement within 4 months.

Potential Complications with Infliximab Therapy for Neurosarcoidosis

The effectiveness of infliximab in treating neurosarcoidosis notwithstanding, the biologic is not without challenges. Chronic immunosuppression can cause patients to become susceptible to opportunistic infections, and another recent case study highlights the potential for fatal complications with infliximab therapy.

The study’s authors report the case of a patient with neurosarcoidosis who was treated with infliximab and dexamethasone who presented with progressive cognitive decline. A magnetic resonance imaging scan of the brain showed ring-enhancing lesions, and infection was suspected.⁴

The care team held immunosuppression and treated the patient with empiric antifungal therapy, but the patient’s neurological and respiratory condition deteriorated rapidly, and the patient died from respiratory failure. An autopsy revealed the presence of invasive aspergillosis.

The report’s authors highlight the fact that treatment with infliximab can have serious complications, including difficult-to-identify and difficult-to-treat invasive aspergillosis. More studies, they write, will be needed to identify the risks associated with infliximab in patients with neurosarcoidosis in order to improve patient outcomes.

References

1. Blume C, Tuleta I, Nolte K, et al. Neurosarcoidosis as a rare differential diagnosis for single or multiple lesions of the nervous system. Br J Neurosurg. 2018;8:1-5. doi: 10.1080/02688697.2018.1506094.

2. Riller Q, Cotteret C, Junot H, et al. Infliximab biosimilar for treating neurosarcoidosis: tolerance and efficacy in a retrospective study including switch from the originator and initiation of treatment [published online February 9, 2019]. J Neurol. doi: 10.1007/s00415-019-09234-y.

3. Tan I, Malinzak M, Salama AKS. Delayed onset of neurosarcoidosis after concurrent ipilimumab/nivolumab therapy. J Immunother Cancer. 2018;6(1):77. doi: 10.1186/s40425-018-0390-2.

4. Van Sanford C, Obeidat AZ, Hagen M, Zabeti A. A case of fatal invasive aspergillosis in a patient with neurosarcoidosis treated with infliximab [published online November 15, 2018].

Int J Neurosci. doi: 10.1080/00207454.2018.1544130.