Comparison of methotrexate with placebo in the treatment of systemic sclerosis: a 24 week randomized double-blind trial, followed by a 24 week observational trial
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In this study, methotrexate (MTX) was compared with placebo in the treatment of systemic sclerosis (scleroderma, SSc) in a 24 week randomized double-blind trial, followed by an observational trial of 24 weeks duration. Twenty-nine scleroderma patients were allocated to receive weekly injections of either 15 mg MTX or placebo. Patients who responded favourably after 24 weeks continued with the same regimen for a further 24 weeks; those who showed a poor response on placebo were allocated to further treatment with 15 mg MTX weekly, and those who responded poorly to treatment with 15 mg MTX had their doses increased to 25 mg. A favourable response was defined as an improvement of total skin score (TSS) by > or = 30%, of single breath diffusion capacity (DLCO) by > or = 15%, or of the score on a visual analogue scale of general well-being (VAS) by > or = 30%, provided that such improvements were not accompanied by persistent digital ulcerations or worsening of DLCO > or = 15%. Seventeen patients were allocated to MTX treatment and 12 to treatment with placebo. After 24 weeks, a significantly larger number of patients receiving MTX (n = 8, 53%) who completed the first 24 weeks of the study had responded favourably compared to patients receiving placebo (n = 1, 10%, P = 0.03). Comparison of separate variables between the two treatment groups by intention-to-treat analysis at week 24 showed improvement in the MTX group of TSS (P = 0.06) and creatinine clearance (P = 0.07). At week 48, 13 patients received MTX from the start of the study and nine during 24 weeks. From these 22 patients, 15(68%) responded favourably and compared with the start of the study they showed significant improvement of TSS (P = 0.04), VAS (P = 0.02), grip strength of the right hand (P = 0.02) and ESR (P = 0.01). Although the number of patients enrolled in this study is small, these results suggest that in a group of patients with active systemic sclerosis, low-dose MTX seems to be more effective than placebo according to pre-defined response criteria.
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Two randomized controlled trials and their reanalysis have shown that methotrexate improves skin score in early diffuse systemic sclerosis.
“According to the same recommendations, two RCTs 148,149 and their reanalysis have shown that MTX improves skin score in early diffuse SSc.”
From Autoimmune diseases and immune-checkpoint inhibitors for cancer therapy: Review of the literature and personalized risk-based prevention strategy (2020) · cites this paper as [148]
Positive effects of methotrexate on other organ manifestations in systemic sclerosis have not been established.
“Positive effects on other organ manifestations have not been established.”
From Autoimmune diseases and immune-checkpoint inhibitors for cancer therapy: Review of the literature and personalized risk-based prevention strategy (2020) · cites this paper as [148]
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- Authors
- VAN DEN HOOGEN, F. H. J., BOERBOOMS, A. M. T., SWAAK, A. J. G., RASKER, J. J., VAN LIER, H. J. J., & VAN DE PUTTE, L. B. A.
- Affiliations
- Radboud University Nijmegen (NL)
- Daniel den Hoed Kliniek (NL)
- Medisch Spectrum Twente (NL)
- ORCID
- RASKER, J. J.
- Venue
- Rheumatology
- Publisher
- Oxford University Press (OUP)
- Published
- 1996
- Volume
- 35
- Issue
- 4
- Pages
- 364-372
- ISSN
- 1462-0324 (ISSN-L)
- 1462-0332
- OpenAlex
- W2149183272
- Cited by
- 355
- References
- 30
- Citations by year
- 2026: 6 · 2025: 11 · 2024: 15 · 2023: 14 · 2022: 14 · 2021: 13 · 2020: 14 · 2019: 11 · 2018: 13 · 2017: 17 · 2016: 25 · 2015: 12 · 2014: 7 · 2013: 16 · 2012: 8
- FWCI
- 2.51
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Lara D. Veeken (publishedVersion)
- PubMed (publishedVersion)
- University of Twente Research Information (publishedVersion, other-oa)
- Radboud Repository (Radboud University) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion, other-oa)
- University of Twente Research Information (submittedVersion, other-oa)
- Funders
- ReumaNederland
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Systemic Sclerosis and Related Diseases
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Pulmonary Hypertension Research and Treatments
- Health Sciences › Medicine › Rheumatology › Dupuytren's Contracture and Treatments
- Keywords
- systemic sclerosis, methotrexate, placebo comparison, skin thickness, lung function, diffusing capacity for carbon monoxide, digital ulcers, creatinine clearance, grip strength, erythrocyte sedimentation rate, treatment response, dose escalation, immunosuppressive therapy, well-being, hand function
- MeSH terms
- Adult, Aged, Double-Blind Method, Female, Humans, Male, Methotrexate, Middle Aged, Scleroderma, Systemic, Severity of Illness Index, Time Factors, Treatment Outcome, Antirheumatic Agents
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