Pruritus associated with systemic sclerosis: a systematic review of treatment-based clinical trials

Clinical Snapshot

Key Findings

• P Value: Not reported at the systematic review level; individual study p-values not synthesised

• Effect Size: No pooled effect size calculable; qualitative findings only. Oral lenabasum (cannabinoid receptor agonist) demonstrated pruritus improvement in a phase II RCT. Low-dose opioid receptor modulators and rituximab showed qualitative pruritus improvement across included studies.

• Primary Outcome: Pruritus severity and relief in patients with systemic sclerosis across multiple therapeutic interventions

• Nnt Or Sensitivity: Not calculable from available data; no NNT, sensitivity, or hazard ratio reported at the review level

• Confidence Interval: Not reported — no meta-analysis performed

Clinical Application

Feasibility of applying these findings in routine clinical practice is currently limited. Lenabasum is not yet approved for SSc in most jurisdictions and remains investigational. Rituximab, while used off-label in SSc for fibrotic and immunological manifestations, is not specifically indicated for pruritus. Low-dose opioid receptor modulators (e.g., low-dose naltrexone) are accessible but lack robust SSc-specific evidence. Standardised pruritus assessment tools (e.g., Numerical Rating Scale, 5-D Itch Scale) should be incorporated into routine SSc clinical assessments. In Australia, rituximab is PBS-listed for several autoimmune conditions but not specifically for SSc or SSc-associated pruritus, requiring off-label use with associated access barriers. Lenabasum is not TGA-approved and is not available outside clinical trials in Australia. Low-dose naltrexone is not PBS-listed and is typically compounded, limiting accessibility. The RACGP and Australian Rheumatology Association (ARA) do not currently have specific guidelines for pruritus management in SSc. Australian clinicians managing SSc should consider incorporating validated pruritus assessment (e.g., NRS, 5-D Itch Scale) into routine multidisciplinary SSc reviews, consistent with the review's recommendations. Referral to dermatology or specialist itch clinics may be appropriate for refractory cases. Adults with systemic sclerosis (both diffuse and limited cutaneous subtypes) experiencing clinically significant pruritus. Findings are most directly applicable to patients in whom pruritus is a prominent symptom affecting quality of life and where standard symptomatic measures have been insufficient.

Abstract

This paper aims to examine the latest research on treatments for itch (pruritus) in people with systemic sclerosis (SSc), identify areas where information is lacking, and propose suggestions for future studies.A comprehensive literature search was performed in PubMed and Scopus in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to identify studies evaluating therapeutic interventions for pruritus in SSc. Eligible studies included randomized controlled trials, cohort studies, and case series comprising a minimum of three patients. Data extraction encompassed study design, patient demographics, pruritus assessment instruments including validated and non-validated measures, and clinical outcomes. Studies were excluded if they concerned localized scleroderma, irrelevant populations, case reports, systematic reviews, lacking relevant outcome data, or incomplete trials. Ten studies met criteria, evaluating immunomodulatory agents, mast cell stabilizers, opioid receptor antagonist, and lysophosphatidic acid receptor antagonists. Pruritus assessment varied and was often secondary to fibrosis outcomes. Oral lenabasum improved pruritus in a phase II trial; low-dose opioid receptor modulators and rituximab also showed qualitative improvement. Pruritus is a frequently overlooked yet clinically significant symptom in systemic sclerosis (SSc) that negatively impacts patients' quality of life. Existing evidence regarding effective therapeutic options remains limited. Future research should prioritize pruritus as a predefined outcome and utilize validated assessment instruments to inform treatment strategies and enhance patient quality of life.

References

1. 1.Mortezaei, K., Pasula, R., Nursoy, M., Syal, A., Panayiotou, I., Kumari, G., Chatzitoffis, A., Milutinovic, P., Fadugba, O. O., & Derk, C. T. (2026). Pruritus associated with systemic sclerosis: a systematic review of treatment-based clinical trials. Rheumatology International. Advance online publication. https://doi.org/10.1007/s00296-025-05842-4