Abstract: 【Abstract】 Objective To evaluate the clinical equivalence between a domestic calcipotriol/betamethasone dipropionate ointment and the originator product in the treatment of stable plaque psoriasis. Methods A multicenter, randomized, double-blind, three-arm, parallel-group, active- and placebo-controlled study was conducted, and 449 patients aged 18 - 65 years with stable plaque psoriasis were enrolled from 25 hospitals （such as the First Affiliated Hospital of China Medical University）. Eligible patients had a baseline physician's global assessment （PGA） score of ≥ 3 points, baseline body surface area （BSA） involvement of 5% - 30%, and a target lesion psoriasis area and severity index （TL-PASI） for plaque elevation of ≥ 3 points. Participants were randomly assigned in a 2:2:1 ratio to the test group （n = 179）, reference group （n = 180）, and placebo group （n = 90）, and applied the domestic calcipotriol/betamethasone dipropionate ointment, originator product, and ointment base respectively, once daily in the evening for 4 weeks. Efficacy and safety were assessed at weeks 1, 2, and 4. The primary efficacy endpoints were the treatment success rates and clinical success rates in each group at week 4. The per-protocol set （PPS） was used for the primary efficacy analysis, and the intention-to-treat （ITT） set for supplementary efficacy analysis. Equivalence between the test and reference preparations was tested using the Cochran-Mantel-Haenszel method adjusted for randomization strata. Superiority of the test and reference preparations over the placebo was also tested. Measurement data were compared among the 3 groups using analysis of variance or non-parametric tests, while treatment success rates, clinical success rates, and incidence rates of adverse reactions were compared using the chi-square test. Results The ITT, PPS, and safety sets included 447, 420, and 448 patients, respectively. In the ITT set, patients were aged 43.6 ± 12.8 years, including 320 （71.6%） males and 127 （28.4%） females, and the disease duration was 11.21 ± 9.05 years; 316 （70.7%） had a PGA score of 3 points and 131 （29.3%） had a PGA score of 4 - 5 points. No significant differences in the baseline characteristics （including age, sex, disease duration and disease severity） were observed among the 3 groups （all P > 0.05）. Based on the PPS analysis, the treatment success rates were 57.9% （99/171） in the test group, 50.3% （86/171） in the reference group, and 7.7% （6/78） in the placebo group, and the clinical success rates were 57.9% （99/171）, 50.3% （86/171）, and 10.3% （8/78）, respectively; both the test and reference groups were superior to the placebo group in both treatment and clinical success rates （all P < 0.001）; the rate differences for treatment success （90% confidence interval ［CI］: -1.3% - 16.4%） and clinical success （90% CI: -1.3% - 16.3%） between the test and reference groups were entirely within the pre-defined equivalence margin （-20% - 20%）. Subgroup analyses by baseline PGA scores: for patients with a baseline PGA score of 3 points, the treatment success rates in the test, reference, and placebo groups were 60.8% （73/120）, 52.1% （62/119）, and 11.1% （6/54）, respectively, and the corresponding clinical success rates were 61.7% （74/120）, 53.8% （64/119）, and 13% （7/54）, respectively; the test and reference groups did not differ significantly in treatment or clinical success rates （both P > 0.05）, but both showed higher success rates than the placebo group （all P < 0.001）; the results of statistical comparisons among the 3 groups in patients with a baseline PGA score of 4 - 5 points were consistent with those observed in patients with a baseline PGA score of 3 points. The percentage reductions in PGA and TL-PASI scores from baseline to weeks 1, 2, and 4 showed significant differences among the 3 groups, which were significantly higher in the test and reference groups than in the placebo group （all P < 0.001）, but did not differ between the test and reference groups （all P > 0.05）. The primary adverse reactions were local skin reactions, such as pruritus, pain, and erythema. The incidence rates of adverse reactions were 8.9% （16/179） in the test group, 7.3% （13/179） in the reference group, and 7.8% （7/90） in the placebo group, with no significant difference among the 3 groups （P > 0.05）. Conclusions The domestic calcipotriol/betamethasone dipropionate ointment demonstrated clinical equivalence to the originator product in the treatment of stable plaque psoriasis, and the two agents exhibited comparable efficacy for patients with varying degrees of disease severity, and were comparable in the speed and degree of clinical improvement, with similar favorable safety profiles.

Key words: Psoriasis, Calcipotriol/betamethasone dipropionate ointment, Clinical equivalence, Vitamin D3 derivatives, Glucocorticoid, Topical compound preparations