Background/Purpose: Digital ulcers (DUs) are a major cause of pain and disability in patients with systemic sclerosis (SSc). Despite the availability of a range of treatment approaches including drug therapies, DUs are often slow to heal, and many patients experience recurrent digital ulceration. Assessment of DU burden is hugely challenging in both clinical practice and clinical trials resulting in a major barrier to the development of new and optimized treatment approaches for DUs. The aim of this scoping review of the literature was to evaluate the domains of illness studied, and the range of instruments and outcome measures used in clinical studies of DUs in patients with SSc.

Methods: Embase, MEDLINE and Cochrane Central Register of Controlled Trials were searched for all articles written in the English language relating to SSc-associated DUs. Two reviewers (MH & NM) independently screened the abstracts. A minimum of 15 participants for DU imaging-derived studies and 25 participants for questionnaire-based studies was required for inclusion. Basic laboratory and genetic studies, and studies of pediatric/juvenile SSc were excluded. There was no limitation by intervention, comparator, or study setting. All primary and secondary outcomes measured and instruments used in each study were recorded along with the study characteristics, including date of publication, sample size, interventions, and study types.

Results: A total of 4869 manuscripts was identified with 1126 duplicates excluded. Of the remaining 3743 abstracts, 123 were eligible for full-text review, and 40 were included in the final analysis. Most studies were either randomized controlled trials (n=13) or non-randomized prospective (n=12) or retrospective (n=8) studies. There was wide variation in the sample sizes of the intervention/actively studied (n=8 to 1439) and comparator (n=9 to 186) arms of the studies. Active interventions included oral/intravenous drugs therapies (n=25), topical/local treatments (n=4), and surgical interventions (n=2).

Domains and instruments/measurements used to study DUs in SSc are presented in Table 1. Half the studies assessed either the count/number of DUS (n=23) or improvement in DU (n=20). Functional impact of DUs was examined in 25% (n=10) of studies assessed. Other outcomes were related to complications of DU (n=7), pain (n=6), health-related quality of life (n=4), microvascular assessment/pathophysiology (n=4), or global DU assessment (n=2). For each outcome, there was significant heterogeneity regarding the types and number of instruments/measurements used within and between studies (Table 1).

Conclusion: This review identified a broad range of disease-related domains and associated outcome instruments/measurements used to study SSc-DUs, including in randomized clinical trials. There has been significant heterogeneity in outcomes used by investigators to study the impact of SSc-DUs.

These data will inform the ongoing work of the OMERACT Vascular Disease in Systemic Sclerosis Working Group to define a core set of disease domains to capture the burden of SSc-DUs.

Table 1. Domains and outcome instruments/measurements used in clinical research studying digital ulcers in systemic sclerosis.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/outcome-reporting-in-systemic-sclerosis-related-digital-ulcers-a-scoping-review/