medwireNews: Tapering of adalimumab may be possible for some patients with rheumatoid arthritis (RA) in sustained remission, but additional research is needed to predict which groups are most suitable for this approach, phase 4 study findings indicate.
The PREDICTRA trial, by Paul Emery (University of Leeds, UK) and colleagues, also found that not all patients who flare during tapering can regain remission when adalimumab is reinstated.
Writing in the Annals of the Rheumatic Diseases, the authors say their results “suggest that tapering of [biologic] DMARDs is only a viable option for a subset of patients.”
They add: “Attempts to define this subset of patients based on baseline clinical and imaging characteristics associated with the occurrence of flare were not successful in this study.”
In all, 122 participants (mean age 60 years, 75% women) with RA who had been receiving adalimumab 40 mg every other week for at least 1 year and had been in stable clinical remission for at least 6 months were randomly assigned, after a 4-week lead-in period, to undergo adalimumab tapering (to 40 mg every 3 weeks; n=102) or withdrawal (switch to placebo; n=20) for 36 weeks.
The individuals had a mean active disease duration of 12.9 years and had been in sustained remission – defined as a DAS28-ESR or DAS28-CRP below 2.6 points – for 2.2 years, on average.
During the course of the study, 36% of patients in the tapering group and 45% of those in the withdrawal group experienced a flare (DAS28-ESR >2.6 points and an increase >0.6 points from baseline or DAS28-ESR increase ≥1.2 points from baseline, regardless of absolute value).
The low number of flares meant that median time to flare was not reached in either arm, but the researchers calculated that the time taken for a quarter of patients to experience a flare was 18.0 weeks in the taper arm compared with just 13.3 weeks in the withdrawal arm.
Logistic regression analyses found no significant association between the odds for developing a flare and either baseline hand and wrist synovitis or bone marrow edema, as measured by magnetic resonance imaging (MRI).
However, Emery et al note that the patients were enrolled on the basis of their sustained clinical remission and had low inflammation on MRI at baseline. “[T]his homogeneity in low scores may have limited the ability of this study to demonstrate a relationship between objectively assessed MRI inflammation and flare,” they remark.
Nonetheless, there were also no associations between flares and any other baseline variables, such as serum adalimumab concentrations and antibody status.
Among patients who experienced a flare, 62% of those in the tapering arm and 50% of those in the withdrawal arm were not back in clinical remission after 16 weeks of open-label rescue adalimumab.
Emery and team conclude: “These findings further support the notion that not all patients do well after [biologic] DMARD tapering or withdrawal, or regain disease control if reinitiation of therapy is required, especially with long-standing disease.”
medwireNews is an independent medical news service provided by Springer Healthcare. © 2020 Springer Healthcare part of the Springer Nature Group