Background/Purpose: anti-histidyl-tRNA synthetase (anti-Jo1) antibodies are found in approximately 25–30% of patients with idiopathic inflammatory myopathies, frequently in the frame of an anti-synthetase syndrome characterized (in addition to the myositis) by the association of interstitial lung disease (ILD, one of the main prognostic factor), arthritis, Raynaud’s phenomenon and mechanic’s hands. The recommended treatment is high dose corticosteroids in association with an immunosuppressant. Nevertheless, some patients remain refractory. We tested the efficacy of rituximab in this situation.

Methods: we conducted a prospective, multicenter, open, phase II study (ClinicalTrials.gov: NCT00774462) of rituximab (1g at day 0 (D0), 15 and month 6). Inclusion criteria were myositis as defined by the 119th ENMC workshop (Hoogendijk JE, et al. Neuromuscul Disord 2004;14:337-45) with anti-Jo1 antibodies, refractory to conventional treatments (i.e. failure, lack of efficacy or major side effects of prednisone and at least two immunosuppressants, leading the physician to a DMARD decision). Endpoints were evaluated at month 12 (M12).

Results: 12 patients were enrolled (8 men, median (IQR) age 50 (32 to 59)). The delay between diagnosis/first treatment and inclusion was 23 months (12 to 45). Patients already received in average 3 lines of treatments (2 to 4). Associated treatments with rituximab were prednisone (n=12), methotrexate (n=1), azathioprine (n=6), intravenous immunoglobulins (n=4), mycophenolate mofetil (n=2) and cyclophosphamide (n=1). Eleven patients completed the study and one was lost of follow-up after 3 weeks. No particular side effects due to rituximab were observed.

Muscle weakness evaluated by the manual testing (Kendall’s test on 10 muscles,) was 94.5 (range 75 to 100) at D0. Only 1 patient had normal strength (=100) at DO, and 6 patients at M12. Median creatine kinase (CK) was 1331 U/l (range 32 to 11718) at D0. Only 1 patient had normal CK level (< 190 U/l) at D0, and 9 patients at M12. Effort dyspnea was noticed in 7/12 patients at D0 and 4/11 at M12. At DO, pulmonary tests showed, median FVC: 72% (46 to 117), FEV1: 69% (46 to 104) and DLCO/VA ratio: 73 (43 to 127). At M12, on the 6 patients who completed functional respiratory tests, 3 presented an increase by more than 10% of their FVC, FEV1 or DLCO/VA. Arthritis were observed in 9/12 patients at D0 vs. 4/11 at M12. Anti-Jo1 antibody titers remained stable over time, with no seronegativation. Finally, at M12 on 11 patients, the burden of associated treatments was unchanged (n=1) or even increased (n=4) in 5 patients but was slimmed-down for 6 patients.

Conclusion: in the difficult situation of long past history of refractory anti-synthetase syndrome with anti-Jo1 antibodies, rituximab seems effective in ~ 50% of the cases permitting a reduction of immunosuppressants. This effect is observed on muscle strength, ILD and arthritis. Rituximab should now be evaluated in a phase III trials in this homogenous group of patients.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/efficacy-of-rituximab-for-the-treatment-of-refractory-inflammatory-myopathies-associated-with-anti-histidyl-trna-synthetase-antibodies-the-force-jo1-study/