Seronegative spondyloarthritis as a complication of anti-CD20 monoclonal antibody treatment in multiple sclerosis

Anti-CD20 monoclonal antibodies (mAbs) have rarely been associated with seronegative spondyloarthritis (SpA). We report nine cases of de novo SpA occurring in the context of anti-CD20 mAb treatment for multiple sclerosis (MS).

Records at two MS referral centres were reviewed to identify patients who developed symptoms of and were formally diagnosed with SpA after starting ofatumumab or ocrelizumab between January 2021 and September 2024. Further review of clinic databases was undertaken to determine the prevalence of SpA in the total clinic population, and those treated with and without anti-CD20 mAbs.

The annual incidence of de novo SpA in anti-CD20 mAb treated patients was 570 per 100,000. Mean age was 50 (± 14.8) years and the median time to symptom onset was 4 (2.5-7.5) months. Seven patients were treated with ofatumumab and two with ocrelizumab. Three stopped the anti-CD20 mAb due to arthritis. After a median follow up of 18 (IQR 9-24) months, five patients have ongoing SpA symptoms. After 12 and 18 months, two patients treated with anti-interleukin 17A mAbs alone have stable MS. In the total clinic population of 3400 patients, the prevalence of SpA was 3.3 % among patients treated with anti-CD20 mAbs, compared to 1.4 % in those who were not. Patients treated with anti-CD20 mAbs had 3.43 times higher odds of developing SpA compared to those who did not receive this treatment (95 % CI: 1.95-6.04, p < 0.0001).

There is a significant association between anti-CD20 mAb treatment and SpA in people with MS. The incidence of SpA in this group is over nine times greater than the highest estimates for the general population. MS patients may be at greater risk of this autoimmune complication due to overlap in genetic risk. More research is required to determine optimal treatment strategies, with anti-IL17A mAbs of particular interest given their safety, and potential benefit, in MS.