Predictors of disease activity and structural progression after treatment with adalimumab plus methotrexate or continued methotrexate monotherapy in patients with early rheumatoid arthritis and suboptimal response to methotrexate

Abstract

ObjectivesMethotrexate is considered to be first-line therapy for rheumatoid arthritis (RA). However, a substantial proportion of treated patients do not achieve the desired goals of therapy. This analysis aimed to identify predictors of insufficient response to methotrexate in patients with early RA.MethodsThe Optimal Protocol for Treatment Initiation with Methotrexate and Adalimumab (OPTIMA) and PREMIER studies in patients with RA for <1 and <3 years, respectively, examined the efficacy of methotrexate and adalimumab in methotrexate-naive patients. This post hoc analysis included patients for whom initial methotrexate monotherapy was not successful after 6 months. Candidate predictors of insufficient response and clinically relevant radiographic progression (CRRP) included demographics, baseline disease characteristics and time-averaged disease variables over a 12-week interval. In OPTIMA, adalimumab was added to therapy after insufficient treatment response; in PREMIER, initial methotrexate therapy was continued; clinical, functional and radiologic outcomes were assessed after 1 year.ResultsBaseline 28-joint Disease Activity Score based on C-reactive protein (DAS28(CRP)) and time-averaged DAS28(CRP) over 4, 8 and 12 weeks were the strongest predictors of insufficient response to methotrexate and CRRP. Addition of adalimumab to methotrexate therapy was associated with better clinical, functional and radiographic outcomes after 1 year compared with continuing on methotrexate monotherapy.ConclusionsIn patients with early RA, baseline disease characteristics and early disease activity can predict response to methotrexate treatment and radiographic progression at 6 months. The addition of adalimumab at 6 months after methotrexate failure is associated with improved outcomes. These results support treatment-to-target strategies and timely adaptation of therapy in patients with early RA.Trial registration numberNCT00420927, NCT00195663; Post-results.

Validation of a Prognostic Multivariable Prediction Model for Insufficient Clinical Response to Methotrexate in Early Rheumatoid Arthritis and Its Clinical Application in Evidencio

“…We externally validated the model for the first time in its entirety as, besides the clinical and laboratory predictors, the lifestyle predictors (BMI and smoking) were also examined in the U-Act-Early cohort (as opposed to the initial validation in the MTX-Rotterdam cohort, which lacked the life-style predictors) [ 9 ]. The strongest predictor was high disease activity at baseline (DAS28 > 5.1) confirming previous findings [ 7 , 18 ]. Due to differences in treatment intensities (i.e., MTX dose and co-medication) between the derivation and the validation cohort, we investigated whether the model was applicable at 6 months despite step-up treatments after the 3-month mark.…”

Pooled analysis of TNF inhibitor biosimilar studies comparing radiographic progression by disease activity states in rheumatoid arthritis

“…Increased disease activity at baseline is also associated with disease activity at 6 months and radiographic progression. This was shown by the ASPIRE, OPTIMA and PREMIER post hoc analysis, which revealed that baseline disease activity by composite measures was the strongest predictor of insufficient response to MTX and radiographic progression at 6 months as well as at 1 year 10 46 47. Taken together with our results, it is suggested that a significant portion of the progression occurs in the first few months, and baseline disease activity plays a role in clinical and radiographic response.…”

Overlapping Sjogren’s syndrome reduces the probability of reaching target in rheumatoid arthritis patients: a propensity score matched real-world cohort from 2009 to 2019

“…2010 witnessed the formal publication of treat-totarget (T2T) recommendation, and the T2T approach has been proved to yield superior outcomes to standard care in RA [14,15]. Besides, there are many factors influencing the response to RA treatment including age, gender, RA duration, rheumatoid factor (RF) and anticitrullinated peptide antibody (ACPA) status, and baseline disease activity [16,17]. To explore the effect of overlapping SS on the therapeutic response in RA patients, we used propensity score matching (PSM) to correct those possible confounding factors.…”