Combination regimens of topical calcipotriene in chronic plaque psoriasis - Systematic review of efficacy and tolerability

Objective: To examine the efficacy and tolerability of calcipotriene combin ed with phototherapy br systemic therapies compared with monotherapy for th e treatment of chronic plaque psoriasis. Design: Quantitative systematic review of 11 randomized controlled trials i nvolving a total of 756 patients with plaque psoriasis. Main Outcome Measures: Rate ratios (RRs) for marked improvement or clearanc e in patient and investigator overall assessments of response; mean differe nce in percentage change in Psoriasis Area and Severity Index; and RRs for clearance in patient and investigator overall assessments of response. Adve rse effects were estimated with the RR and the rate difference in terms of withdrawal rate, proportion of patients experiencing adverse events, and pr oportion of patients with cutaneous and noncutaneous adverse effects. Results: Antipsoriatic effects of acitretin, cyclosporine, and psoralen-UV- A phototherapy were enhanced with the addition of topical calcipotriene usi ng the Psoriasis Area and Severity Index as the outcome, but this is not tr anslated into an increase in the number of patients who achieve at least ma rked improvement. At the end of treatment, the RRs for marked improvement o r clearance in patient assessments were as follows: calcipotriene plus acit retin vs acitretin alone (12 weeks), 1.4 (95% confidence interval [CI], 1.0 -1.9); calcipotriene plus cyclosporine vs cyclosporine alone (6 weeks), 1.2 (95% Ci, 0.9-1.6); and calcipotriene plus psoralen-UV-A vs psoralen-W-A al one (12 weeks), 1.2 (95% CI, 0.9-1.6). Patients were also no more likely to obtain marked improvement or better with calcipotriene plus W-B therapy th an with UV-B therapy alone (RR, 1.0; 95% CI, 0.8-1.1 at 8 weeks in the pati ent assessment). There is limited evidence that use of calcipotriene might reduce the cumulative exposure to phototherapy and systemic treatment. Duri ng the short duration of these trials, there were no significant difference s in withdrawal rates or adverse effects between the combined regimens arid their corresponding monotherapy control interventions. Conclusions: Overall, there is insufficient evidence to support any large e ffects in favor of combination treatment. In the patient assessments, the r esults do not show an adjuvant effect, but there is some evidence that use of calcipotriene might reduce cumulative exposure to systemic therapy to ob tain clearance. There were no longterm morbidity data on the effectiveness of any of the combinations studied. Given that psoriasis is a chronic recur rent disease for most patients, longer trials are needed to determine wheth er the addition of topical calcipotriene to systemic therapy improves the r isk-benefit ratio by reducing the long-term risk of toxic effects. Equally important is the need to examine the impact of such combinations on the dur ation of remission after treatment.