Rituximab in early systemic sclerosis

Abstract

Objectives(1) Hypothesis testing of the potency of rituximab (RTX) in preventing fibrotic complications and (2) assessing acceptability and feasibility of RTX in early systemic sclerosis (SSc).MethodsA small, 24-month, randomised, double-blind, placebo-controlled, single-centre trial in patients with SSc diagnosed <2 years was conducted. Patients received RTX or placebo infusions at t=0, t=15 days and t=6 months. Patients were clinically evaluated every 3 months, with lung function tests and high-resolution CT every other visit. Skin biopsies were taken at baseline and month 3. Immunophenotyping of peripheral blood mononuclear cells was performed at every visit, except at months 9 and 18. Adverse events, course of skin and pulmonary involvement and B cell populations in skin and peripheral blood were evaluated.ResultsIn total 16, patients (rituximab n=8, placebo n=8) were included. Twelve patients had diffuse cutaneous SSc. Eighty-eight adverse events (RTX n=53, placebo n=35, p=0.22) and 11 serious adverse events (RTX n=7, placebo n=4, p=0.36) occurred. No unexpected RTX-related events were observed. Mean skin score over time did not differ between the groups. Over time, forced vital capacity and extent of lung involvement slightly improved with RTX, but this difference was insignificant. In peripheral blood B cells depletion was demonstrated.ConclusionsNo unexpected safety issues were observed with RTX in early SSc. Although this small trial could not confirm or reject potential efficacy of RTX in these patients, future placebo-controlled trials are warranted, specifically in the subgroup of patients with pulmonary involvement.Trial registration numberEudraCT 2008-07180-16; Results.

Efficacy, Safety, and Tolerability of Treatments for Systemic Sclerosis-Related Interstitial Lung Disease: A Systematic Review and Network Meta-Analysis

“…We excluded 42 studies (Abou-Raya, A., 2013 [ 29 ]; Allanore, Y., 2018 [ 30 ]; Allanore, Y., 2019 [ 31 ]; ASSET, 2019 [ 32 ]; ASSIST, 2011 [ 33 ]; Boonstra, M., 2017 [ 34 ]; Chakravarty, E.F., 2015 [ 35 ]; Daoussis, D., 2010 [ 36 ]; Daoussis, D., 2012 [ 37 ]; Daoussis, D., 2017 [ 38 ]; Denton, C., 2007 [ 39 ]; EDITA, 2019 [ 40 ]; FaSScinate, 2016 [ 41 ]; FocuSSced, 2020 [ 42 ]; Gordon, J.K., 2018 [ 43 ]; Gruber, B.L., 1991 [ 44 ]; Guillevin, L., 1982 [ 45 ]; Guo, H.M., 2008 [ 46 ]; Henes, J., 2020 [ 47 ]; Herrick, A.L., 2017 [ 48 ]; Hoffmann-Vold, A.M., 2019 [ 49 ]; Khanna, D., 2009 [ 50 ]; Khanna, D., 2019 [ 50 ]; Mehrabi, S., 2019 [ 51 ]; Nadashkevich, O., 2008 [ 52 ]; NCT02283762 [ 53 ]; NCT02465437 [ 54 ]; NCT02745145 [ 55 ]; Pakas, J., 2002 [ 56 ]; Panopoulos, S.T., 2013 [ 57 ]; Poormoghim, H., 2013 [ 58 ]; Pope, J.E., 2001 [ 59 ]; Prey, S., 2012 [ 60 ]; Quillinan, N.P., 2014 [ 61 ]; Schiopu, E., 2016 [ 62 ]; Sclero XIII, 2019 [ 63 ]; Seibold, J.R., 2000 [ 64 ]; Seibold, J.R., 2010 [ 65 ]; Su, T.I.K., 2009 [ 66 ]; Sullivan, A., 2018 [ 67 ]; van den Hoogen, F.H.J., 1996 [ 68 ]; van Laar, J.M., 2014 [ 69 ]). Reasons for exclusion are described in the Supplementary material 2.1, pages 25–26 .…”

Monitoring patients with systemic lupus erythematosus: general characteristics and discussion questions (according to the Canadian Rheumatology Association recommendations)

“…Как правило, в эти исследования включались больные с диффузной формой ССД на ранней стадии, когда индурация кожи является доминирующим симптомом. Исключениями можно считать два небольших исследования (оба с группами сравнения без лечения), в которых изменений плотности кожи (по модифицированному кожному счету Роднана) между группами не было [5,29]. активности было ожидаемым изменение СОЭ и СРБ, которые изначально были повышенными, хотя и умеренно.…”

Immunotherapy of systemic sclerosis

“…84 The double-blind RCT study by Boonstra M et al also examined 16 early (<2years disease duration) scleroderma patients. 82 Patients treated with Rituximab showed moderately improvement, although not statistically significant, of lung function compared to patients on placebo. Skin score did not differ between groups.…”

“…Skin score did not differ between groups. 82 On the contrary, Thiebaut M et al in their retrospective study of 53 patients (13 from a single centre in France combined with data from 40 additional patients retrieved from published cases) concluded that RTX improves skin, and lung function. 83 Currently RTX is considered in cases with worsening ILD following treatment with CyP.…”

“…Among 20 relevant references found in the literature, 11 had less than ten patients and/or no comparison group. The remain 9 studies were: 1 open label RCT with two years follow up, 78,79 1 open label comparative study, 80 1 retrospective nested case-control study, 81 1 double-blind RCT with 2 years follow-up, 82 1 retrospective study in a single centre combined with literature review of published cases, 83 and 3 prospective open label studies. [84][85][86] The first study showed improvement in mRSS and lung function tests (FVC and DLCO) 78 and further improvement observed after two years of follow up.…”