In individuals with rheumatoid arthritis (RA), flare following reduction or withdrawal of biologic disease-modifying antirheumatic drug (bDMARD) dose may lead to radiographic progression. These findings were recently published in Rheumatology (Oxford), and the researchers highlighted the importance of monitoring for relapse symptoms. 

This double-blind interval of the PRESERVE study included 1535 participants (n=531 with Disease Activity Score in 28 joints [DAS28] relapse, n=502 with clinical disease activity index [CDAI] relapse, and 502 with simplified disease activity index [SDAI] relapse). Participants were adults on methotrexate with persistent moderate RA, and all were given weekly etanercept 50 mg in addition to methotrexate for 36 weeks. If low disease activity was achieved by week 36, participants were randomly assigned to 52 weeks of etanercept 50 mg and methotrexate, etanercept 25 mg and methotrexate, or placebo and methotrexate. Participants with and without flare were compared post hoc for radiographic progression (defined as the change in modified total Sharp score of at least 0.5 units per year) using a chi-squared test. Results were also compared between placebo and intervention groups. 

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Methotrexate monotherapy was associated with higher rates of flare compared with combination therapies, with radiographic progression of 17% vs 9% (P <.001), respectively, and a DAS28 relapse rate of 62% vs 21% (P <.0001), respectively. Among those given combination therapies, flare was also associated with higher radiographic progression compared with no flare (P <.01). Worse outcomes were also associated with flare when it was defined by SDAI and CDAI guidelines (P <.05).

Limitations to this study included a post hoc study design, a small number of patients in each subgroup, a lack of adjustments for multiple comparisons, and a 1-year analysis period.


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Study researchers concluded that “[withdrawing] bDMARDs may be successful in some patients who achieve [low disease activity] or remission with full-dose bDMARD therapy, reducing the risk [for] dose-dependent side effects and treatment costs without loss of efficacy. However, as shown in these analyses of the PRESERVE study population, a substantial proportion of patients will not achieve sustained disease control after [etanercept] withdrawal. Moreover, the likelihood of joint damage is greater in those who discontinue biologic therapy than in those who continue it.”

This study was funded by Wyeth Pharmaceuticals, which is owned by Pfizer. Several authors report financial associations with pharmaceutical companies.

Reference
Smolen JS, Pedersen R, Jones H, Mahgoub E, Marshall L. Impact of flare on radiographic progression after etanercept continuation, tapering or withdrawal in patients with rheumatoid arthritis
[published online June 30, 2019]. Rheumatology (Oxford). doi: 10.1093/rheumatology/kez224