Biologic Dose Reduction
At Point of Care
In the recent HIT-HARD study, treatment-naive patients received combination adalimumab plus MTX compared with MTX alone (at a dose of 15 mg weekly) for 24 weeks, after which adalimumab was discontinued and all patients continued on MTX monotherapy for another 24 weeks. Most patients did not maintain low disease activity after discontinuing adalimumab. Patients who had initially received adalimumab plus MTX had less radiographic progression, even after discontinuation of adalimumab.
An observational study assessed whether patients (N=51) with stable RA and low disease activity, defined as DAS28 <3.2, could have their infliximab dose reduced or discontinued. Dose was reduced from a mean of 3 mg/kg every 8 to 12 weeks in 25% increments until discontinuation or flare. In 16% (CI 6%–26%) and 45% (CI 31%–59%), infliximab could be discontinued or downtitrated, while in 39% downtitration was not possible. Over the course of the study, the mean infliximab dose was reduced from 3.0 mg/kg to 1.7 mg/kg. Mean DAS28 scores increased from 2.5 to 2.8.72
One-year results from the HONOR study suggested that in some patients who had attained sustained remission with adalimumab plus MTX treatment, adalimumab could be withdrawn for up to 1 year and MTX monotherapy continued. In this study, 52 of the 75 patients who maintained DAS28 erythrocyte sedimentation rate–defined remission for 6 months were considered evaluable, and of these, 48% maintained adalimumab-free remission. All patients who experienced low disease activity during the year after discontinuation maintained structural remission. Among patients who experienced flare during the year following discontinuation, radiographic progression was absent in most cases (83%).73
UPDATE 2/6/15 Remission was maintained for 12 months by more than half of patients who tapered or discontinued DMARD treatment in the prospective phase III RETRO study. END UPDATE
UPDATE 2/15 The DOSEFLEX trial reported comparable efficacy between 2 dosing regimens of certolizumab pegol maintenance treatment (400 mg every 4 weeks and 200 mg every 2 weeks) and both regimens were superior to placebo.