Yiu Zenas Z N, Smith Catherine H, Laws Philip, Hampton Philip J, Griffiths Christopher E M, Warren Richard B
Centre for Dermatology Research, Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom.
The Dermatology Centre, Salford Royal Hospital, Northern Care Alliance NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom.
JAMA Dermatol. 2025 Jun 4. doi: 10.1001/jamadermatol.2025.1463.
It is unclear whether concomitant methotrexate enhances the effectiveness and persistence of adalimumab for psoriasis. The recent OPTIMAP randomized clinical trial that tested adalimumab against adalimumab with methotrexate could not adequately answer this question due to underrecruitment.
To determine the effectiveness of using methotrexate with adalimumab in people with plaque psoriasis.
DESIGN, SETTING, AND PARTICIPANTS: This target trial emulation cohort study replicated key aspects of the OPTIMAP trial design using the British Association of Dermatologists Biologics and Immunomodulators Register between 2007 and 2021.
Adalimumab, 40 mg, every other week monotherapy (comparator) vs adalimumab, 40 mg, every other week and methotrexate weekly, with the dosage as determined by the clinician (intervention).
The primary outcome was the difference in the adalimumab survival function at 1 year. The secondary outcomes included differences in adalimumab survival function at 3 years; 75% reduction in Psoriasis Area and Severity Index (PASI75) at 1 year and 3 years; serious adverse events at 1 and 3 years; and adalimumab concentrations and antidrug antibodies at 1 year. Inverse probability treatment and censoring weighting were used for covariate and missing outcome adjustment. Flexible parametric survival models were fitted for survival outcomes and generalized linear models for other outcomes.
There were 231 and 1553 participants (754 female individuals [42.3%]) in the intervention (median [IQR] age, 43.7 [35.1-53.1] years) and comparator (median [IQR] age, 43.6 [34.2-52.0] years) arms, respectively. Drug survival for the comparator arm at 1 year was 78.1% (95% CI, 76.1%-80.2%) and the intervention arm was 79.1% (95% CI, 71.8%-87.2%), with no evidence of difference (1.0%; 95% CI, -7.0% to 8.9%). PASI75 at 1 year and 3 years in the comparator arm was 52.0% (95% CI, 47.7%-56.3%) and 32.4% (95% CI, 28.0%-36.8%), respectively; in the intervention arm, PASI75 was 49.4% (95% CI, 31.5%-67.3%) and 37.2% (95% CI, 16.8%-57.6%), respectively. There was no evidence of differences at 1 year and 3 years (-2.5%; 95% CI, -21.0% to 15.9% and 4.9%; 95% CI, -16.1% to 25.7%, respectively). There was no evidence for a difference between the 2 arms for serious adverse events and adalimumab concentrations, while the intervention arm had a lower antidrug antibody level (risk difference, -123.7 AU/mL; 95% CI, -200.5 to -46.9).
The results of this cohort study suggest that there was no evidence of a difference in the effectiveness and persistence of adalimumab in people with psoriasis between monotherapy and adalimumab with concomitant methotrexate.
甲氨蝶呤与阿达木单抗联合使用是否能提高阿达木单抗治疗银屑病的有效性和持久性尚不清楚。最近一项比较阿达木单抗与阿达木单抗联合甲氨蝶呤的OPTIMAP随机临床试验，由于入组人数不足，未能充分回答这个问题。
确定甲氨蝶呤与阿达木单抗联合使用对斑块状银屑病患者的有效性。
设计、地点和参与者：这项目标试验模拟队列研究使用英国皮肤科医师协会生物制剂和免疫调节剂登记处2007年至2021年的数据，复制了OPTIMAP试验设计的关键方面。
阿达木单抗，40mg，每两周一次单药治疗（对照）与阿达木单抗，40mg，每两周一次，甲氨蝶呤每周一次，剂量由临床医生确定（干预）。
主要结局是1年时阿达木单抗生存函数的差异。次要结局包括3年时阿达木单抗生存函数的差异；1年和3年时银屑病面积和严重程度指数（PASI75）降低75%；1年和3年时的严重不良事件；以及1年时阿达木单抗浓度和抗药抗体。采用逆概率治疗和删失加权法进行协变量和缺失结局调整。对生存结局采用灵活的参数生存模型，对其他结局采用广义线性模型。
干预组有231名参与者（754名女性个体[42.3%]）（年龄中位数[四分位间距]，43.7[35.1 - 53.1]岁），对照组有1553名参与者（年龄中位数[四分位间距]，43.6[34.2 - 52.0]岁）。对照组1年时药物生存率为78.1%（95%置信区间，76.1% - 80.2%），干预组为79.1%（95%置信区间，71.8% - 87.2%），无差异证据（1.0%；95%置信区间，-7.0%至8.9%）。对照组1年和3年时的PASI75分别为52.0%（95%置信区间，47.7% - 56.3%）和32.4%（95%置信区间，28.0% - 36.8%）；干预组1年和3年时的PASI75分别为49.4%（95%置信区间，31.5% - 67.3%）和37.2%（95%置信区间，16.8% - 57.6%）。1年和3年时均无差异证据（分别为-2.5%；置信区间，-21.0%至15.9%和4.9%；95%置信区间，-16.1%至25.7%）。两组在严重不良事件和阿达木单抗浓度方面无差异证据，而干预组抗药抗体水平较低（风险差异，-123.7 AU/mL；95%置信区间，-200.5至-46.9）。
这项队列研究结果表明，在银屑病患者中，单药治疗的阿达木单抗与阿达木单抗联合甲氨蝶呤在有效性和持久性方面没有差异证据。
