Sustained remission rates at 1 year were not significantly affected by a programmed infliximab treatment strategy, according to research published in the Annals of the Rheumatic Diseases.
Researchers sought to determine whether a programmed treatment strategy in which the infliximab dose is adjusted based on baseline serum tumor necrosis factor-α (TNF-α), induces clinical remission after 54 weeks plus subsequent infliximab discontinuation for 1 year. The study (Remission induction by Raising the dose of Remicade in RA [RRRR]) was an open-label, parallel-group, multicenter, randomized, controlled trial conducted in Japan between April 2011 and September 2013.
Eligible participants were randomly assigned 1:1 to receive either standard or programmed infliximab treatment. The programmed treatment dose was based on 3 categories of baseline TNF-α levels: low <0.55 pg/mL; intermediate ≥0.55 pg/mL and <1.65 pg/mL, and high ≥1.65 pg/mL. Patients in the standard treatment arm received 3 mg/kg of infliximab at 0, 2, and 6 weeks after trial enrollment, and every 8 weeks thereafter.
In total, 337 patients were enrolled in the RRRR study and randomly assigned to a treatment group (167 patients to standard treatment and 170 patients to programmed treatment). Within the programmed treatment arm, 51, 68, and 51 patients were allocated into the low, intermediate, and high TNF-α groups, respectively. In total, 120 and 117 patients in the standard and programmed treatment arms completed treatment to 54 weeks.
At 54 weeks, differences in the least squares mean for both the simplified disease activity index (SDAI) and the disease activity score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR) were not statistically significant. After 54 weeks, clinical remission proportions via SDAI in each arm were 32.3% and 39.4% (standard and programmed treatment, respectively). By DAS28-ESR, clinical remission proportions were 31.1% and 40% in each group, respectively. Overall, 52 and 67 patients in each group began infliximab treatment discontinuation.
Investigators found that the proportion of sustained infliximab discontinuation 1 year after the 54-week discontinuation was not significantly different between the groups (21.6% and 23.5% in the standard and programmed treatment arms, respectively; 2.2% difference; 95% CI, -6.6% to 11%; P =.631).
Within the programmed treatment arm, the rates of sustained discontinuation at 1 year were 21.6%, 23.5%, and 25.5% in the TNF-low, intermediate, and high groups, with no statistically clear trend in terms of infliximab dose. Primary reasons for ceasing discontinuation included the reintroduction of infliximab, the introduction of other biologic antirheumatic drugs, and clinical judgment.
Researchers used a logistic regression model to evaluate the associations between baseline characteristics and sustained 1-year remission in both treatment arms. In each arm, SDAI <26.0 was “a statistically significant predictor of sustained discontinuation,” according to investigators (odds ratios 2.83% and 2.97%; 95% CI, 1.24-6.50 and 1.37-6.43 in the standard and programmed treatment arms, respectively). Additionally, rheumatoid factor less than 45, baseline TNF-α higher than 1.65, and baseline methotrexate dose lower than 10 mg/kg were also statistically significant predictors of 1-year remission in the standard treatment arm.
Study limitations include technical, ethical, and budgetary issues, resulting in the necessitation of different numbers of vials of infliximab needing to be prepared and the use of health insurance coverage by included participants.
“In order to facilitate decision-making by patients and rheumatologists, more efforts are needed to determine the patient profile most likely to benefit from discontinuation of biological [disease-modifying antirheumatic drugs],” the researchers concluded.
Disclosure: This clinical trial was supported by Mitsubishi Tanabe Pharma Co, Ltd. Please see the original reference for a full list of authors’ disclosures.
Tanaka Y, Oba K, Koike T, et al. Sustained discontinuation of infliximab with a raising-dose strategy after obtaining remission in patients with rheumatoid arthritis: the RRRR study, a randomised controlled trial [published online October 19, 2019]. Ann Rheum Dis. doi: 10.1136/annrheumdis-2019-216169