The effectiveness of two-compound formulation calcipotriol and betamethasone dipropionate gel in the treatment of moderately severe scalp psoriasis: A systematic review of direct and indirect evidence

To evaluate the two-compound formulation (TCF) calcipotriol and betamethasone dipropionate (BDP) gel versus other topical therapies for scalp psoriasis in adults using direct and indirect comparisons. A systematic review identified 10 randomised controlled trials (RCTs) of topical treatments used in clinical practice for moderately severe scalp psoriasis. A meta-analysis was undertaken to obtain estimates of clinical effectiveness using recommended efficacy and safety outcome measures. We determined the proportion of responding patients using two definitions: i) 'controlled disease' using the Investigator Global Assessment (IGA) rating scale and ii) a score of 0 or 1 on the Total Sign Score (TSS). Tolerability was extracted in terms of percentages of patients experiencing all adverse events (AEs), skin AEs and withdrawals due to AEs. Direct comparisons were performed where head-to-head data were available. For other comparators where TCF gel was compared indirectly, 'pairs' of trials were compared on the basis of a common comparator using meta-regression in order to derive an indirect comparison estimate, while preserving randomisation within trials. Assumptions of comparability were considered regarding study homogeneity (data can be pooled in a meta-analysis), similarity of trials (clinical and methodological) and consistency of findings from direct and indirect evidence. The meta-analysis showed that TCF gel was statistically significantly more effective than other topical treatments in terms of achieving a response defined according to both IGA and TSS criteria. TCF gel was generally associated with a statistically significant lower risk of AEs, skin AEs or patients withdrawing from RCTs due to AEs. Although direct and indirect evidence in this analysis is sparse, this indirect comparison suggests that the TCF gel has significant benefits over other topical therapies considered in the routine management of patients with moderately severe scalp psoriasis. Despite other analysis limitations in terms of study heterogeneity inevitable across an evidence base spanning decades, these results were consistent, using a number of efficacy and tolerability outcome measures.