Belimumab for the Treatment of Early Diffuse Systemic Sclerosis

Gordon, Jessica; Martyanov, Viktor; Franks, Jennifer M; Bernstein, Elana J.; Szymonifka, Jackie; Magro, Cynthia M.; Wildman, Horatio F.; Wood, Tammara A.; Whitfield, Michael L.; Spiera, Robert

doi:10.1002/art.40358

Cited by 103 publications

(23 citation statements)

References 40 publications

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“…The lungs, heart, kidney, and other organs may also be involved ( 1 , 3 , 4 ). We have previously identified “intrinsic” subsets of SSc (fibroproliferative, inflammatory, limited, and normal-like) based upon skin gene expression ( 5 – 7 ) that may predict response to therapy ( 8 , 9 ). Analysis of skin gene expression across cohorts identified interactions between immune and stromal cells that may act as key drivers of SSc pathogenesis in patients with a permissive genetic background ( 10 , 11 ).…”

Section: Introductionmentioning

confidence: 99%

Regulator combinations identify systemic sclerosis patients with more severe disease

et al. 2020

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Section: Introductionmentioning

confidence: 99%

Regulator combinations identify systemic sclerosis patients with more severe disease

et al. 2020

Self Cite

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“…Its biological activity causes mainly apoptosis of B cells and decreases autoantibody production [ 45 ]. A 52-week, investigator-initiated, single-centre, double-blind, placebo-controlled, pilot study was performed in early (disease duration < 3 years) dcSSc patients recently started on mycophenolate mofetil [ 46 ]. Twenty patients were enrolled and randomized 1:1 to belimumab 10 mg/kg intravenously at a 2-week interval for the first three doses and then at 4-week intervals until week 48 while also on mycophenolate mofetil therapy (1 g twice a day).…”

Section: Resultsmentioning

confidence: 99%

An update on targeted therapies in systemic sclerosis based on a systematic review from the last 3 years

Campochiaro

Allanore

2021

Arthritis Res Ther

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New molecular mechanisms that can be targeted with specific drugs have recently emerged for the treatment of systemic sclerosis (SSc) patients. Over the past 3 years, the achievement of one large phase 3 trial has led to the approval by drug agencies of the first drug licenced for SSc-related interstitial lung disease. Given this exciting time in the SSc field, we aimed to perform a systemic literature review of phase 1, phase 2 and phase 3 clinical trials and large observational studies about targeted therapies in SSc. We searched MEDLINE/PubMed, EMBASE, and ClinicalTrials.gov for clinical studies from 2016 with targeted therapies as the primary treatment in patients with SSc for skin or lung involvement as the primary clinical outcome measure. Details on the study characteristics, the trial drug used, the molecular target engaged by the trial drug, the inclusion criteria of the study, the treatment dose, the possibility of concomitant immunosuppression, the endpoints of the study, the duration of the study and the results obtained were reviewed. Of the 973 references identified, 21 (4 conference abstracts and 17 articles) were included in the systematic review. A total of 15 phase 1/phase 2 clinical trials, 2 phase 3 clinical trials and 2 observation studies were analysed. The drugs studied in phase 1/phase 2 studies included the following: inebilizumab, dabigatran, C-82, pomalidomide, rilonacept, romilkimab, tocilizumab, tofacitinib, pirfenidone, lenabasum, abatacept, belimumab, riociguat, SAR100842 and lanifibranor. All but 3 studies were performed in early diffuse SSc patients with different inclusion criteria, while 3 studies were performed in SSc patients with interstitial lung disease (ILD). Phase 3 clinical trials investigated nintedanib and tocilizumab. Nintedanib was investigated in SSc-ILD patients whereas tocilizumab focused on early diffuse SSc patients with inflammatory features. Two observational studies including > 50 patients with rituximab as the targeted drug were also evaluated. All these studies offer a real hope for SSc patients. The future challenges will be to customize patient-specific therapeutics with the goal to develop precision medicine for SSc.

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“…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 .…”

Section: Resultsmentioning

confidence: 99%

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

Erre

Sebastiani

Fenu

et al. 2020

JCM

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Background: There is a paucity of head-to-head comparisons of the efficacy and harms of pharmacological treatments for systemic sclerosis-related interstitial lung disease (SSc-ILD). Methods: We conducted a network meta-analysis (NMA) in order to compare the effects of different treatments with the placebo on change in forced vital capacity (FVC), change in diffusion lung capacity for CO (DLCO), serious adverse events (SAEs), discontinuation for adverse events and mortality in SSc-ILD. Standardized mean difference (SMD) and log odds ratio were estimated using NMA with fixed effects. Results: Nine randomized clinical trials (926 participants) comparing eight interventions and the placebo for an average follow-up of one year were included. Compared to the placebo, only rituximab significantly reduced FVC decline (SMD (95% CI) = 1.00 (0.39 to 1.61)). Suitable data on FVC outcome for nintedanib were not available for the analysis. No treatments influenced DLCO. Safety and mortality were also not different across treatments and the placebo, although there were few reported events. Cyclophosphamide and pomalidomide were less tolerated than the placebo, mycophenolate, and nintedanib. Conclusion: Only rituximab significantly reduced lung function decline compared to the placebo. However, direct head-to-head comparison studies are required to confirm these findings and to better determine the safety profile of various treatments.

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Belimumab for the Treatment of Early Diffuse Systemic Sclerosis

Cited by 103 publications

References 40 publications

Regulator combinations identify systemic sclerosis patients with more severe disease

Regulator combinations identify systemic sclerosis patients with more severe disease

An update on targeted therapies in systemic sclerosis based on a systematic review from the last 3 years

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

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