Safety and efficacy of Rituximab in systemic sclerosis: A systematic review and meta-analysis.

PURPOSE Rituximab is widely prescribed to treat systemic sclerosis (SSc) by the depletion of pathogenic B cells. Nonetheless, the clinical benefit of Rituximab in SSc remains contentious. This meta-analysis was conducted to systematically evaluate the safety and efficacy profile of Rituximab in SSc patients. PATIENTS AND METHODS We performed a systematic online query in PubMed, Cochrane, and Web of Science. The available studies on the use of Rituximab in SSc patients were comprehensively reviewed and investigated. RESULTS In total, 14 studies, including 597 participants, were analyzed. Pooled results showed the long-term improvement in the modified Rodnan skin score (mRSS) for skin function (ΔmRSS: 7.00 at 6 months, 9.70 at 12 months, and 10.93 at 24 months), while forced vital capacity (FVC) (ΔFVC: -0.69 at 6 months, -2.62 at 12 months, and -0.67 at 24 months) and diffusing capacity of the lungs for carbon monoxide (DLCO) (ΔDLCO: -2.39 at 6 months, -3.28 at 12 months, and -0.79 at 24 months) for lung function remained stable in SSc patients after Rituximab treatment. The rate of Rituximab-related adverse events was 12% in the pooled results. CONCLUSION The pooled results of this meta-analysis indicated that Rituximab is well tolerated, and it is able to improve cutaneous function and stabilize pulmonary function in SSc patients.

[1]  Daniel C. Lee,et al.  Getting to the heart of the matter: detecting and managing cardiac complications in systemic sclerosis , 2019, Annals of the rheumatic diseases.

[2]  Sarah Crunkhorn.  Epigenetic mechanism of systemic sclerosis , 2019, Nature Reviews Drug Discovery.

[3]  M. Boubaya,et al.  Outcomes of patients with systemic sclerosis treated with rituximab in contemporary practice: a prospective cohort study , 2019, Annals of the rheumatic diseases.

[4]  S. Sridhar,et al.  Baseline Plasma Cell Gene Signature Predicts Improvement in Systemic Sclerosis Skin Scores Following Treatment With Inebilizumab (MEDI‐551) and Correlates With Disease Activity in Systemic Lupus Erythematosus and Chronic Obstructive Pulmonary Disease , 2018, Arthritis & rheumatology.

[5]  Radleigh G. Santos,et al.  Memory B Cells Activate Brain-Homing, Autoreactive CD4+ T Cells in Multiple Sclerosis , 2018, Cell.

[6]  Bodi D Zhang.  Ofatumumab , 2018, Reactions Weekly.

[7]  E. Hachulla,et al.  Efficacy and safety of rituximab in systemic sclerosis: French retrospective study and literature review. , 2018, Autoimmunity reviews.

[8]  M. de Pauw,et al.  Two years follow-up of an open-label pilot study of treatment with rituximab in patients with early diffuse cutaneous systemic sclerosis , 2018, Acta clinica Belgica.

[9]  A. Yoshizaki.  Pathogenic roles of B lymphocytes in systemic sclerosis. , 2018, Immunology letters.

[10]  A. Akdoğan,et al.  Rituximab Experience in Patients With Long-standing Systemic Sclerosis–Associated Interstitial Lung Disease: A Series of 14 Patients , 2017, Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases.

[11]  Diana Romero.  Haematological cancer: Extended EFS with rituximab , 2017, Nature Reviews Clinical Oncology.

[12]  C. Denton,et al.  SYSTEMIC SCLEROSIS , 2008 .

[13]  T. Lancet.  Systemic sclerosis: advances and prospects , 2017, The Lancet.

[14]  M. Flather,et al.  Rituximab versus cyclophosphamide for the treatment of connective tissue disease-associated interstitial lung disease (RECITAL): study protocol for a randomised controlled trial , 2017, Trials.

[15]  Y. Asano,et al.  Unprecedented success of rituximab therapy for prednisolone- and immunosuppressant-resistant systemic sclerosis-associated interstitial lung disease , 2017, Scandinavian journal of rheumatology.

[16]  A. Drosos,et al.  A multicenter, open-label, comparative study of B-cell depletion therapy with Rituximab for systemic sclerosis-associated interstitial lung disease. , 2017, Seminars in arthritis and rheumatism.

[17]  K. Patra,et al.  Safety and tolerability of an anti-CD19 monoclonal antibody, MEDI-551, in subjects with systemic sclerosis: a phase I, randomized, placebo-controlled, escalating single-dose study , 2016, Arthritis Research & Therapy.

[18]  A. Antonelli,et al.  Rituximab in the treatment of patients with systemic sclerosis. Our experience and review of the literature. , 2015, Autoimmunity reviews.

[19]  C. Denton,et al.  The Pathogenesis of Systemic Sclerosis. , 2015, Rheumatic diseases clinics of North America.

[20]  G. de Luca,et al.  Long-term efficacy of B cell depletion therapy on lung and skin involvement in diffuse systemic sclerosis. , 2015, Seminars in arthritis and rheumatism.

[21]  S. Hsieh,et al.  Rituximab for refractory digital infarcts and ulcers in systemic sclerosis , 2014, Clinical Rheumatology.

[22]  D. Huscher,et al.  Effects and safety of rituximab in systemic sclerosis: an analysis from the European Scleroderma Trial and Research (EUSTAR) group , 2014, Annals of the rheumatic diseases.

[23]  P. Emery,et al.  An extra dose of rituximab improves clinical response in rheumatoid arthritis patients with initial incomplete B cell depletion: a randomised controlled trial , 2014, Annals of the rheumatic diseases.

[24]  D. Elewaut,et al.  Two-year Results of an Open Pilot Study of a 2-treatment Course with Rituximab in Patients with Early Systemic Sclerosis with Diffuse Skin Involvement , 2013, The Journal of Rheumatology.

[25]  A. Chaudhuri.  Ocrelizumab in multiple sclerosis: risks and benefits , 2012, The Lancet.

[26]  Sanjiv J. Shah,et al.  Autologous non-myeloablative haemopoietic stem-cell transplantation compared with pulse cyclophosphamide once per month for systemic sclerosis (ASSIST): an open-label, randomised phase 2 trial , 2011, The Lancet.

[27]  G. Pignataro,et al.  Neuroprotective, immunosuppressant and antineoplastic properties of mTOR inhibitors: current and emerging therapeutic options. , 2011, Current opinion in pharmacology.

[28]  R. Fischer-Betz,et al.  Safety and clinical outcomes of rituximab therapy in patients with different autoimmune diseases: experience from a national registry (GRAID) , 2011, Arthritis research & therapy.

[29]  Ami A. Shah,et al.  Long-term experience of mycophenolate mofetil for treatment of diffuse cutaneous systemic sclerosis , 2011, Annals of the rheumatic diseases.

[30]  G. Tarantino,et al.  Analytical and pharmacological aspects of therapeutic drug monitoring of mTOR inhibitors. , 2011, Current drug metabolism.

[31]  G. Ferraccioli,et al.  B cell depletion in diffuse progressive systemic sclerosis: safety, skin score modification and IL-6 modulation in an up to thirty-six months follow-up open-label trial , 2010, Arthritis research & therapy.

[32]  C. Kalogeropoulou,et al.  Experience with rituximab in scleroderma: results from a 1-year, proof-of-principle study , 2009, Rheumatology.

[33]  P. Merkel,et al.  B cell depletion with rituximab in patients with diffuse cutaneous systemic sclerosis. , 2009, Arthritis and rheumatism.

[34]  Venetoclax-Obinutuzumab Elicits High Response Rates in CLL. , 2019, Cancer discovery.

[35]  V. Vilela,et al.  Rituximab for the therapy of systemic sclerosis: a series of 10 cases in a single center. , 2016, Revista brasileira de reumatologia.