Adding low-dose methotrexate (MTX) to adalimumab therapy for adults with chronic plaque psoriasis may enhance treatment effectiveness and increase adalimumab drug survival against anti-drug antibodies, according to results of a single-blind randomized controlled trial published in the Journal of Investigative Dermatology.
Investigators randomly assigned adult patients with chronic plaque psoriasis 1:1 to treatment with either adalimumab plus MTX 10 mg once weekly (ADL-MTX group) or adalimumab monotherapy (ADL group). Patients needed to be adalimumab-naïve and have a Psoriasis Area Severity Index (PASI) score of greater than 8 to participate in the study. Clinical safety, efficacy, pharmacokinetic, and immunogenicity assessments were performed at baseline and at weeks 5, 13, 25, 37, and 49, or at early termination, respectively. The primary endpoint was adalimumab drug survival at the final first-year study visit (week 49), assessed using Kaplan-Meier curves.
Investigators included 66 patients in the trial and randomly assigned 33 to the ADL-MTX group and 33 to the ADL group. In the ADL-MTX group, 30 patients were followed up for the 49-week study period including 11 who discontinued the study medication prematurely, mostly due to adverse events, and 1 who never started MTX. In the ADL group, 28 patients were followed up for the entire study period including 12 who did not remain on the study treatment regimen, mostly due to psoriasis exacerbation or adverse events. The majority of patients in both groups were men, and the mean age at baseline for both groups was around 48 years.
After 13 weeks of treatment, more patients in the ADL-MTX group continued adalimumab therapy with a cumulative drug survival of 74.2% compared with 58.6% in the ADL group (P =.15). Investigators noted that significantly more patients in the ADL-MTX group achieved PASI 75 than the ADL group at week 5 (22.6% vs 3.5%; P =.05). This difference did not remain significant at week 49 (P =.13). More patients achieved PASI 90 in the ADL-MTX group (29%) than the ADL group (16.7%) at week 49, but this difference was not significant (P =.34).
Median improvement in PASI score was greater in the ADL-MTX group at week 5 (8.5, IQR: 5.1-9.8) compared with the ADL group (4.1, IQR: 2.1-6.6; P <.01), but was not significant at other time points. The percentage of patients meeting treatment goals was significantly higher in the ADL-MTX group at week 13 (P =.03), but was not significantly different at weeks 25 and 49. Mean change in Dermatology Life Quality Index (DLQI) by week 49 was comparable between the groups.
In terms of safety, no serious treatment-emergent adverse events occurred overall, and at least 1 or more adverse events were reported by 85.2% of all patients with no major differences between groups. In the ADL-MTX group, gastrointestinal disturbance and fatigue appeared to occur most frequently, and infections and headache were slightly more common in the ADL group.
For pharmacokinetic endpoints, adalimumab median serum-trough concentrations were not significantly higher in the ADL-MTX group compared with the ADL group at all timepoints. At week 5, significantly more patients in the ADL group failed to reach adalimumab serum concentrations above 3.2 mg/l than in the ADL-MTX group, but this difference was not significant at week 49. “Good responders (PASI > 75) had higher serum adalimumab trough concentrations” than non-or moderate responders at week 49 in both groups, it was written.
The study was limited as it did not reach the calculated target sample size of 93 patients.
“Owing to the pragmatic trial design, we expect that our findings can be extrapolated directly to daily clinical practice and support guidance on the use of adalimumab combination therapy with MTX,” the study authors wrote.
Disclosure: Several study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
van der Kraaij G, Busard C, van den Reek J, et al. Adalimumab with methotrexate vs. adalimumab monotherapy in psoriasis: first-year results of a single-blind randomized controlled trial. J Invest Dermatol. 2022;142(9):2375-2383.e6. doi:10.1016/j.jid.2022.01.033