Ustekinumab, an Interleukin (IL)-12 and IL-23 Inhibitor, Effectively Treats Psoriatic Arthritis (PsA) Independent of Methotrexate Combination Therapy Based on Change in Disease Activity Score 28 (DAS28) Did. Advantages of adding or maintaining methotrexate at initiation of ustekinumab include: lancet.1
“Methotrexate is thought to have several mechanisms of action that help ameliorate inflammatory arthritis, including inhibition of the interleukin (IL)-12 and IL-23 pathways,” the researchers explained. increase.
In a randomized, multicenter, placebo-controlled, phase 3b combination methotrexate efficacy, safety, and impact on adherence to ustekinumab treatment in patients with active psoriatic arthritis (MUST) trial (NCT03148860), investigators investigated evaluated the role of methotrexate in combination with , help treat PsA. Eligible patients were ustekinumab-naive, met the criteria for PsA classification, and had active her PsA.
Conducted in 22 centers in Germany between January 2017 and April 2021, patients were randomized 1:1 to receive ustekinumab (45 mg; 90 mg for patients weighing >100 kg). and placebo (15 mg weekly) or methotrexate (15 mg weekly). The primary outcome was non-inferiority of mean disease activity score-28 joints (DAS28) based on erythrocyte sedimentation rate (ESR) at week 24 for ustekinumab monotherapy compared with ustekinumab plus methotrexate therapy. Yes, which was further stratified by current methotrexate treatment versus previous methotrexate treatment. The secondary endpoint was non-inferiority of his DAS28 at week 52. Both adverse events (AEs) and serious AEs (SAEs) were reported.
Ultimately, 173 adult patients with active PsA were included in the study and assigned to receive concomitant methotrexate (n = 88) or placebo (n = 85). At baseline, 84 patients were currently receiving methotrexate treatment, and 89 patients were methotrexate-naïve. The majority (96%, n = 166) were included in the safety and efficacy analysis at 24 weeks. His average age was 48.2 years, and his 58% of patients were male.
Results showed that ustekinumab monotherapy was not inferior to ustekinumab plus methotrexate in terms of DAS28 at week 24 (2.9 [SD 1.31] vs 3.1 [1.42]). The stratified Mann-Whitney estimator for comparisons between treatment groups was 0.5426 (two-sided 95% CI 0.4545–0.6307). Similarly, the 52-week mean DAS28 was 2.8 (SD 1.4) in the monotherapy group and 3.1 (SD 1.6) in the methotrexate combination group. The stratified Mann-Whitney estimator was 0.5461 (95% CI 0.4579 to 0.6344). His DAS28 difference between the two treatment groups at week 24 was 0.29. Additionally, 44% of patients in the methotrexate cohort and 46% of patients in the monotherapy cohort achieved his DAS28 remission at 24 weeks.
SAEs were reported in 9% (n = 7) of patients in the monotherapy group and 9% (n = 8) of patients in the combination therapy group.
The study was slightly under-study as 173 patients were ultimately included from an original sample size of 196. The researchers also noted that DAS28 did not include the full range of signs and symptoms of her PsA disease activity. Misstratification may have occurred in persons with previous methotrexate exposure and nonadherence to treatment. Finally, common methotrexate-related side effects, such as nausea, may have allowed patients to decide to blind treatment.
“The analysis suggests that ustekinumab, with or without concomitant methotrexate, is highly effective in reducing disease symptoms in multiple domains,” the researchers concluded. Use of methotrexate in psoriatic arthritis may be indicative of disease severity and prolonged disease duration in some patients, but when used in combination with ustekinumab for the treatment of psoriatic arthritis, It does not appear to be beneficial. Eliminating methotrexate from ustekinumab therapy may reduce the cost and burden for patients.”
Koehm M, Rossmanith T, Foldenauer AC, et al. Methotrexate plus ustekinumab versus ustekinumab monotherapy in patients with active psoriatic arthritis (MUST): a randomized, multicenter, placebo-controlled, phase 3b, non-inferiority trial. Lancet rheumatism. 2023;5(1):e14-e23.doi:10.1016/S2665-9913(22)00329-0