Background Clinical remission or low disease activity (LDA) are now realistic targets in the management of patients with rheumatoid arthritis (RA), especially in early disease and thanks to biologic treatments. The subsequent handling of biologic therapy after remission or LDA has been achieved however remains unclear, and possibility of discontinuation of tumor necrosis factor (TNF) inhibitors may become an important issue with relevant safety and economy issues.
Objectives To assess the currently available data on the risk of relapse after TNF inhibitors withdrawal in patients with LDA.
Methods We conducted a systematic literature review and assessed available articles published (up to December 2013) in Medline/Pubmed, and presented at ACR and EULAR congresses from 2010 to 2013. The primary endpoint was the comparison in proportions of patients who had relapsed at 52 weeks after either discontinuation or maintain of TNF inhibitors, in RA patents who had achieved at least LDA state with anti-TNF agents. Relapse was defined as DAS28>3.2 or DAS28CRP>2.7. The Mantel-Haenszel method was used to provide a pooled odds-ratio (OR) estimate and a 95% confidence interval (CI) in “discontinuation” versus “maintain the treatment” groups. Statistical heterogeneity was assessed by χ2 test.
Results The literature search identified 81 articles and 7 congress abstracts, of which 5 articles and 3 abstracts could be included in the study according to predefined requirements. Among these, 3 articles (BRIGHT , PRESERVE , OPTIMA ) and 1 abstract (DOSERA ) met the criteria to allow meta-analysis. After discontinuing TNF inhibitors, the proportion of relapse ranged across the studies from 19% to 87% in “discontinuation” group, and from 9% to 48% in “maintain the treatment”. The meta-analysis showed a significantly increased risk of relapse after drug withdrawal (OR 1.97 (95%CI 1.12-3.48), with substantial heterogeneity due to study OPTIMA, which differed from others by disease duration (i.e. including patients with earlier disease).
Conclusions This meta-analysis shows a significantly increased risk of relapse after discontinuation of TNF inhibitors in RA patients who had achieved LDA under this treatment. Further evaluation of other options, especially progressive tapering of the biologic drug, might be a more efficient option to decrease drug exposure.
BRIGHT: Harigai and al, Mod Rheumatol. 2012; 22(6):814-22.
PRESERVE: Smolen and al, Lancet. 2013; 381(9870):918-29.
OPTIMA: Smolen and al, Lancet. 2014; 383:321–32
DOSERA: Van Vollenhoven [abstract]. Arthritis Rheum 2012; 64:4171.
Disclosure of Interest None declared