Adalimumab dose tapering is associated with fewer disease flares than complete adalimumab withdrawal in patients in long-standing clinical remission from rheumatoid arthritis (RA), according to study data published in the Annals of Rheumatic Disease. Time to flare was also slightly longer in patients who tapered than in those who withdrew.
The PREDICTRA study (Phase 4 Trial Assessing the Impact of Residual Inflammation Detected via Imaging Techniques, Drug Levels and Patient Characteristics on the Outcome of Dose Tapering of Adalimumab in Clinical Remission Rheumatoid Arthritis [RA] Subjects; ClinicalTrials.gov Identifier: NCT02198651) was a double-blind randomized clinical trial conducted at 54 sites in Australia, Canada, Europe, and the United States. Patients with RA who were receiving adalimumab 40 mg every other week for ≥12 months and who were in stable clinical remission were eligible for inclusion.
Stable remission was defined as a 28-joint Disease Activity Score based on erythrocyte sedimentation rate (DAS28-ESR) or C-reactive protein of <2.6 for ≥6 months. Exclusion criteria were current use of biological disease-modifying antirheumatic drugs (bDMARDs) other than adalimumab or having a medical condition that precluded contrast-enhanced magnetic resonance imaging (MRI).
Consenting patients were enrolled in a 4-week, open-label lead-in period, during which they received adalimumab 40 mg every other week. Patients who maintained a DAS28-ESR of <2.6 throughout the 4-week taper period were randomly assigned 5:1 to either the adalimumab taper group (40 mg every 3 weeks) or adalimumab withdrawal group (placebo dose every 3 weeks) for 36 weeks. Patients who experienced a flare were reassigned to a rescue group, through which they received adalimumab 40 mg every other week for up to 16 weeks. A flare was defined as either DAS28-ESR >2.6 and a DAS28-ESR increase of >0.6 from baseline or a DAS28-ESR increase of ≥1.2 from baseline. Hand and wrist synovitis and bone marrow edema were measured by MRI. The association between MRI-detected inflammation and flare occurrences was assessed using multivariable logistic regression.
Of 146 patients treated during the open-label lead-in period, 122 were randomly assigned to the taper (n=102) and withdrawal (n=20) groups. The majority of participants were women (n=91; 75%). Patients had a mean 12.9±10.0 years of active disease, 5.4±3.3 years of adalimumab exposure, and 2.2±2.0 years of sustained RA remission. Flares were experienced by 37 (36%) and 9 (45%) patients in the taper and withdrawal groups, respectively. Time to flare was generally lower in the withdrawal group than in the taper group.
Per regression analyses, baseline synovitis and bone marrow edema were not significantly associated with flare occurrence in the taper group. Clinical remission was maintained by 86% and 85% of patients in the taper and withdrawal groups, respectively, who remained in the study through week 40. Among patients who experienced a flare, 38% in the taper group and 50% in the withdrawal group regained disease control after 16 weeks of adalimumab rescue therapy. Time to regain disease control was 4.1 weeks in the taper group and 10.6 weeks in the withdrawal group. No new safety signals were observed during the trial. Adverse events occurred at similar rates between study groups.
Taken together, these data demonstrated the feasibility of adalimumab tapering in patients with RA in long-standing remission. Patients in the tapering group experienced numerically fewer flares than patients in the withdrawal group. Time to flare was also longer in the tapering group, though not significantly so.
The study findings were limited by the small cohort size and relatively low baseline inflammation of enrollees, which may have limited the performance of imaging results to predict flare occurrence in this population.
“Tapering bDMARDs is an option for a subset of patients who are in deep, long-standing remission, and in case of a flare, previous bDMARD dose can be reinstituted to help regain remission in some but not all patients,” the investigators concluded.
Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Emery P, Burmester GR, Naredo E, et al. Adalimumab dose tapering in patients with rheumatoid arthritis who are in long-standing clinical remission: results of the phase IV PREDICTRA study [published online May 13, 2020]. Ann Rheum Dis. doi:10.1136/annrheumdis-2020-217246