Treat-to-Target Strategy Helps Elderly Patients With Rheumatoid Arthritis

doctor checking elderly patient's X-ray
The efficacy and safety of a treat-to-target strategy using MTX and biologic DMARDs for patients with elderly-onset RA was investigated.

In elderly patients with new-onset rheumatoid arthritis (RA), a treat-to-target (T2T) strategy using methotrexate (MTX) and biologic disease-modifying antirheumatic drugs (bDMARDs) was safe and effective, according to study results published in Rheumatology.

The recommended approach for treatment of patients with RA is based on levels of disease activity and additional patient factors. As limited data exist on the outcomes of T2T strategy for elderly patients, the objective of the current study was to determine the safety and effectiveness of T2T intervention targeting low disease activity (LDA) for elderly patients with RA.

The treatment was modified to target LDA, defined as Simplified Disease Activity Index (SDAI) <11 or disease activity score in 28 joints according to erythrocyte sedimentation rate (DAS28-ESR) <3.2, within 24 weeks. Treatment with MTX and folic acid was initiated with dose increase according to tolerability, followed by a tumor necrosis factor inhibitor (TNFi) as the first bDMARD. The subsequent line of treatment was a different TNFi, tocilizumab, or abatacept.

The primary outcome was clinical remission, defined as SDAI ≤3.2. Secondary outcomes were the proportion of patients achieving LDA, normal physical function (Health Assessment Questionnaire Disability Index [HAQ-DI] ≤0.5), and clinically relevant radiologic progression.

The study included 197 (mean age, 74.4±6.7 years) elderly patients with new-onset RA and moderate-to-high disease activity from the CRANE cohort (Choju registry of RA treated with Non-biologic DMARDs and biologic agents in Elderly patients in Japan).

Nonimplementation of the T2T intervention was defined as lack of European League Against Rheumatism response and no treatment intensification at week 12 or not achieving LDA and no treatment intensification at weeks 24, 36, 52, 76, 104, or 128. Investigators determined the risk for drug exposure — MTX, bDMARDs, and glucocorticoids — after starting T2T intervention, using data totaling 2122 periods of 3 months each from the whole cohort of 197 patients.

A total of 157 (79.7%) of the 197 patients started treatment with MTX at baseline. Of these, 53 (33.8%) patients achieved LDA with a low dose of MTX. During the 3 years of observation, 167 (84.7%) of the 197 patients started MTX at some point, and 82 (41.6%) of these patients received bDMARDs.

In 69 (35%) patients, treatment intensification was not possible because of comorbidities or the patient’s own decision. The remaining 128 patients adhered to T2T intervention throughout the follow-up period.

Patients who adhered to the T2T intervention during the course of the study achieved remission at 50% or greater from week 52 to 156 compared with rates ranging from 8.7% to 34.8% among patients nonadhering to T2T strategy (P =.002).

At week 156, rates of normal physical function, defined as HAQ-DI ≤0.5, were significantly higher in patients adhering to T2T intervention compared with patients who did not adhere to T2T strategy (70.3% vs 43.5%, respectively; P <.001).

During the observation period, there were 89 serious adverse events of any type in 61 patients. According to the statistical analysis, MTX, bDMARDs, and low-dose glucocorticoids did not increase the risk for severe adverse events during the follow-up when adjusted for mean SDAI during the observation period and comorbidities at baseline.

The limitations of the CRANE included the small sample size, potential selection bias, lack of data on risk factors for serious infectious events or the benefits and risks of initial short-term use of glucocorticoids for this group.

“T2T strategy for [elderly-onset RA] by using MTX and bDMARDs was effective with acceptable safety profile. Adhering to T2T led to better outcomes,” concluded the researchers.

Disclosure: Several study authors declared affiliations with the pharmaceutical or biopharma industries. Please see the original reference for a full list of authors’ disclosures.


Sugihara T, Ishizaki T, Onoguchi W, et al. Effectiveness and safety of treat-to-target strategy in elderly-onset rheumatoid arthritis: a 3-year prospective observational study. Rheumatology (Oxford). Published online January 7, 2021. doi: 10.1093/rheumatology/keaa922