Efficacy of Rituximab in Refractory Inflammatory Myopathies Associated with Anti- Synthetase Auto-Antibodies: An Open-Label, Phase II Trial

Abstract

ObjectiveAnti-synthetase syndrome (anti-SS) is frequently associated with myositis and interstitial lung disease (ILD). We evaluated prospectively, in a multicenter, open-label, phase II study, the efficacy of rituximab on muscle and lung outcomes.MethodsPatients were enrolled if they were refractory to conventional treatments (prednisone and at least 2 immunosuppressants). They received 1 g of rituximab at D0, D15, and M6. The primary endpoint was muscular improvement based on manual muscular testing (MMT10, Kendall score in 10 muscles) at M12. Secondary endpoints were normalization of creatine kinase (CK) level, ILD improvement based on forced vital capacity and/or diffuse capacity for carbon monoxide, and number and/or doses of associated immunosuppressants.ResultsTwelve patients were enrolled, and 10 completed the study. Only 2 patients presented an improvement of at least 4 points on at least two muscle groups (primary end-point). Overall, seven patients had an increase of at least 4 points on MMT10. CK level decreased from 399 IU/L (range, 48–11,718) to 74.5 IU/L (range, 40–47,857). Corticosteroid doses decreased from 52.5 mg/d (range, 10–70) to 9 mg/d (range, 7–65) and six patients had a decrease in the burden of their associated immunosuppressants. At baseline, all 10 patients presented with ILD. At M12, improvement of ILD was observed in 5 out of the 10 patients, stabilization in 4, and worsening in 1.ConclusionsThis pilot study of rituximab treatment in patients with refractory anti-SS provided data on evolution of muscular and pulmonary parameters. Rituximab should now be evaluated in a larger, controlled study for this homogenous group of patients.Trial RegistrationClinicaltrials.gov NCT00774462.

Oxygen-Dependent Patient with Antisynthetase Syndrome Associated Interstitial Lung Disease Responds Promptly to Rituximab with Rapid Pulmonary Function Improvement

“…7 In a recent study, not only did rituximab show improvement in pulmonary function but also led to a decrease in total creatine kinase levels, decreased steroid dosage, and decreased usage of immunosuppressive medications. 10 Interestingly, pulmonary function improvement may also be due to muscular strength reinforcement rather than just improvement of ILD itself. 10 During treatment, adverse effects of rituximab were mainly limited to infections, but not severe enough to require hospitalization.…”

“…10 Interestingly, pulmonary function improvement may also be due to muscular strength reinforcement rather than just improvement of ILD itself. 10 During treatment, adverse effects of rituximab were mainly limited to infections, but not severe enough to require hospitalization. 10 Early diagnosis of antisynthetase syndrome along with prompt initiation of the correct treatment regimen is critical to preventing disease progression.…”

“…10 During treatment, adverse effects of rituximab were mainly limited to infections, but not severe enough to require hospitalization. 10 Early diagnosis of antisynthetase syndrome along with prompt initiation of the correct treatment regimen is critical to preventing disease progression. Recent research is limited to case reports and retrospective studies; nevertheless, they indicate treatment with rituximab have shown great efficacy in improving pulmonary function.…”

Guidelines of the Brazilian Society of Rheumatology for the treatment of systemic autoimmune myopathies

“…A multicenter phase II study evaluated the efficacy of rituximab in individuals with SAM with anti-synthetase autoantibodies refractory to conventional treatment (GC and at least two immunosuppressive drugs) demonstrated that the majority of these patients had an increase in the Manual Muscle Testing (MMT)-8 followed by a reduction of CK levels and a reduction in the dose of GC (B) [87].…”

Diagnosis of dermatomyositis: Autoantibody profile and muscle pathology

“…At present, patients with different idiopathic inflammatory myopathies are treated with roughly the same medications. However, in the era when biological (molecular targeted) therapy is becoming a realistic option, it will be reasonable to consider therapeutic strategies separately for distinct subsets . In this context, the diagnostic criteria of myositis, which were formulated by Bohan and Peter in 1975, and are often still used now, do not seem appropriate for the current situation .…”