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Introduction Limited cutaneous systemic sclerosis (lcSSc) is the most prevalent SSc subset and can lead to significant disability and impaired quality of life. Our objective was to review and map the literature regarding the efficacy of drug interventions, including immunosuppressive drugs, to prevent new or progressive complications in lcSSc.Material and Methods The electronic databases MEDLINE, EMBASE and EBM Reviews were searched from cohort inception to August 2024, using terms related to scleroderma, pharmacological interventions and randomized controlled trials (RCTs). Identified papers were screened by two independent reviewers. We included RCTs evaluating the efficacy of pharmacological interventions on clinical outcomes in at least 20 SSc patients, including lcSSc.Results Out of 1816 identified papers, 144 manuscripts met inclusion criteria, including 106 unique trials. Notably, 110 papers were excluded because they included dcSSc patients only, of which 54 would have met inclusion criteria otherwise. Of the 106 unique trials, 33 (31%) reported no data on disease subset distribution, 65 (61%) only reported on the number of lcSSc patients, 3 (2.8%) included only lcSSc patients, and 5 (4.7%) performed lcSSc subgroup analyses. Whereas most vasoactive/vasodilator drug trials included lcSSc participants (94%, n=50), this was the case in a minority of immunosuppressive drug trials (38%, n=11, see figure 1).Among immunosuppressive drug trials, 6 were interstitial lung disease (ILD) trials, with 26% to 64% of study populations being lcSSc patients. One trial performed subgroup analyses and confirmed the efficacy of cyclophosphamide compared to placebo in slowing lung function decline in lcSSc. In addition, a trial of tofacitinib with 40 (61%) lcSSc patients showed that this drug was more effective than low-dose methotrexate in treating skin fibrosis, digital ulcers and arthritis after one year. One small trial examined the effect of methotrexate (15-25 mg weekly) compared to placebo in 29 early SSc patients, of whom 62% had lcSSc, and found a higher rate of >30% improvement in mRSS in the treated group (53% vs 10%) at 24 weeks. One pulmonary arterial hypertension trial of rituximab vs placebo, which included 35 (62%) patients with anti-centromere or anti-Th/To antibodies, found higher 6-minute walking distances at 24 weeks, but otherwise no significant differences in other hemodynamic parameters.Conclusions Few trials have examined the efficacy of immunosuppressive drugs in lcSSc. Further research including lcSSc patients is needed to evaluate the role of immunosuppression and inform management of this highly prevalent subset.Abstract P.283 Figure 1