Systemic pharmacological treatment of digital ulcers in systemic sclerosis: a systematic literature review.

OBJECTIVES: To evaluate the evidence concerning systemic pharmacological treatments for systemic sclerosis (SSc) digital ulcers (DU) to inform the development of evidence-based treatment guidelines.

METHODS: A systematic literature review of seven databases was performed to identify all original research studies of adult patients with SSc DU. Randomised controlled trials (RCTs) and prospective longitudinal observational studies (OBS) were eligible for inclusion. Data was extracted, applying the PICO framework, and risk of bias (RoB) was assessed. Due to study heterogeneity narrative summaries were used to present data.

RESULTS: Forty-seven studies that evaluated the treatment efficacy or safety of pharmacological therapies were identified among 4250 references. Data from 18 RCTs of 1,927 patients and 29 OBS of 661 patients, at various RoB (total 2,588 patients) showed that intravenous iloprost, phosphodiesterase-5 inhibitors and atorvastatin are effective for the treatment of active DU. Bosentan reduced the rate of future DU in two RCTs (moderate RoB) and eight OBS at low to high RoB. Two small studies (moderate RoB) indicate that JAK inhibitors may be effective for the treatment of active DU, otherwise there are no data to support the use of immunosuppression or anti-platelet agents in the management of DU.

CONCLUSION: There are several systemic treatments, across four medication classes, that are effective therapies for the management of SSc DU. However, a lack of robust data means it is not possible to define the optimal treatment regimen for SSc DU. The relatively low quality of evidence available has highlighted further areas of research need.