Testing treat-to-target outcomes with initial methotrexate monotherapy compared with initial tumour necrosis factor inhibitor (adalimumab) plus methotrexate in early rheumatoid arthritis

Abstract

Objectives: To compare responses in patients with early rheumatoid arthritis (RA) initially treated with the tumour necrosis factor inhibitor (TNFi) adalimumab+methotrexate (MTX) versus MTX monotherapy who may have continued receiving MTX or switched to adalimumab rescue therapy after inadequate response to MTX.

Methods: OPTIMA enrolled MTX-naive patients with active RA for <1 year. This post hoc analysis determined the proportion of patients, stratified by initial treatment, who achieved 28-joint modified Disease Activity Score based on C reactive protein <3.2, normal function and/or no radiographic progression at weeks 26, 52 and 78.

Results: Significantly greater proportions of patients initially treated with adalimumab+MTX (n=466) compared with MTX monotherapy (n=460) achieved good clinical (53% vs 30%), functional (45% vs 33%) and radiographic (87% vs 72%) outcomes at week 26. From weeks 26 to 78, adalimumab rescue patients achieved similar clinical and functional outcomes versus patients initially treated with adalimumab+MTX. However, significantly more patients initially treated with adalimumab+MTX had no radiographic progression at weeks 52 and 78 versus patients initially treated with MTX (both timepoints: 86% vs 72%).

Conclusions: In early RA, starting with MTX monotherapy and adding TNFi after 26 weeks yields similar longer term clinical results as starting with TNFi+MTX combination therapy but allows a small but significant accrual of radiographic damage.

Trial registration: ClinicalTrials.gov NCT00420927.

Keywords: anti-tnf; disease activity; early rheumatoid arthritis; methotrexate; treatment.

Conflict of interest statement

Competing interests: AK has provided remunerated expert advice to and received grant/research support for his institution from AbbVie. RFvV has received grants and research support from AbbVie, Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Pfizer, Roche and UCB, and consulting fees and honoraria from AbbVie, AstraZeneca, Biotest, Bristol-Myers Squibb, Celgene, Crescendo, GlaxoSmithKline, Centocor-Janssen, Lilly, Merck, Novartis, Pfizer, Roche, UCB and Vertex. RF provided remunerated expert advice to and received grant support from AbbVie. PE has received research grants and/or consulting fees from AbbVie, Bristol-Myers Squibb, Lilly, Merck, Novartis, Pfizer, Roche, Sandoz and UCB. SF, IS and SC are employees of AbbVie and may hold stock or stock options. BG is a former employee of AbbVie and may hold stock or stock options. HK is an employee of AbbVie Deutschland GmbH & Co KG and may hold stock or stock options. JSS has provided remunerated expert advice to and received grant/research support for his institution from AbbVie.

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Figures

Figure 1

Percentage of patients with clinical, functional and radiographic outcomes stratified by initial treatment regimen. (A) LDA based on DAS28(CRP) 2 test. Missing DAS28(CRP) and HAQ-DI data were imputed using last observation carried forward; missing ΔmTSS data were imputed using multiple imputation. ADA, adalimumab; CRP, C reactive protein; DAS28, 28-joint modified Disease Activity Score; HAQ-DI, Disability Index of the Health Assessment Questionnaire; LDA, low disease activity; mTSS, modified total Sharp score; MTX, methotrexate; PBO, placebo.

Figure 2

Response rates for patients achieving (A) 20%, (B) 50% and (C) 70% improvement in ACR criteria over the course of 78 weeks. *This analysis group included the ADA continuation arm (n=105) and, after scaling to yield a proportional equivalent number of patients, the ADA withdrawal arm (n=102). †Percentage improvement was assessed from week 26. ‡Percentage improvement was assessed from week 52. Missing data were imputed using last observation carried forward. ACR, American College of Rheumatology; ADA, adalimumab; MTX, methotrexate.