Twelve‐Year Retention Rate of First‐Line Tumor Necrosis Factor Inhibitors in Rheumatoid Arthritis: Real‐Life Data From a Local Registry

Abstract

Objective. To evaluate the 12-year survival of the first tumor necrosis factor inhibitor (TNFi) treatment in a cohort of rheumatoid arthritis (RA) patients, comparing the between-groups discontinuation rates for infliximab, etanercept, and adalimumab. Methods. RA patients treated with their first TNFi were investigated from a local registry. Before and after adjusting for propensity scores, overall and by individual TNFi 12-year drug retention was evaluated. Drug survival rates were calculated using the Kaplan-Meier method and compared by the Cox extended model. Subanalyses were performed according to concomitant methotrexate (MTX) and discontinuation reasons. Results. Of 583 patients, 222 were treated with infliximab, 179 with etanercept, and 182 with adalimumab; 33.7% and 26% discontinued the first TNFi because of inefficacy or adverse events, respectively. The overall 12-year drug survival rate for the unmatched population was 23.4%. In the propensity score-adjusted population, the hazard ratio (HR) for treatment discontinuation was significantly greater for adalimumab and infliximab versus etanercept (HR 2.89 [95% confidence interval (95% CI) 2.2-3.78] and HR 2.56 [95% CI 1.92-3.4], respectively), and no difference was found between and for adalimumab versus infliximab (HR 1.16 [95% CI 0.91-1.47]). The incidence of withdrawal due to secondary inefficacy was stable from 3 to 12 years for etanercept, but progressively increased for the monoclonal antibodies. Concomitant MTX significantly increased the survival of both adalimumab and etanercept (HR 1.48 [95% CI 1.18-1.86]). Conclusion. The overall 12-year drug survival rate was 23.4%, being significantly higher for etanercept than adalimumab and infliximab. Etanercept discontinuations for inefficacy did not increase from 3 to 12 years. Concomitant MTX increased adalimumab and etanercept drug survival.

Persistence, switch rates, drug consumption and costs of biological treatment of rheumatoid arthritis: an observational study in Italy

“…Etanercept showed the highest persistence with treatment; at the end of the 4-year follow-up, the number of patients persisting with etanercept treatment was ~1.4 and 1.6 times higher than for infliximab and adalimumab, respectively. This finding is consistent with the results of two important Italian registries, GISEA (Italian Early Arthritis study)23 and LORHEN (Lombardy Rheumatology Network),24 and with another study that, based on a local registry, estimated persistence with therapy at 12 years of the three most commonly used TNF inhibitors for the treatment of RA, showing that the risk of discontinuation for adalimumab (hazard ratio [HR] 2.35 [95% CI 1.73–3.21]) and infliximab (HR 1.55 [95% CI 1.14–2.11]) was significantly greater than for etanercept 25…”

Treatment Outcomes with Biosimilars: Be Aware of the Nocebo Effect

“…In addition, drug profiles play an important role, with patients more likely to discontinue treatment due to a poor side-effect profile or lack of efficacy of a medication [23]. For example, in patients with rheumatoid arthritis, discontinuation rates due to inefficacy and adverse events were demonstrated in etanercept (17.5 and 22.4%, respectively), infliximab (44.1 and 36.7%, respectively) and adalimumab (50.4 and 31.2%, respectively) over a period of 12 years.…”

“…For example, in patients with rheumatoid arthritis, discontinuation rates due to inefficacy and adverse events were demonstrated in etanercept (17.5 and 22.4%, respectively), infliximab (44.1 and 36.7%, respectively) and adalimumab (50.4 and 31.2%, respectively) over a period of 12 years. These data highlight the importance efficacy and safety of a medication plays in patient adherence to treatment [23]. [14].…”

Infection, malignancy, switching, biosimilars, antibody formation, drug survival and withdrawal, and dose reduction

“…First-line biologic treatment survival in a population-based cohort was examined in a large Italian registry of patients with rheumatoid arthritis; the length of time examined (12 years) far exceeded prior attempts [32]. Examining survival for ETN, ADA, and IFX, the data revealed that the incidence of ETN withdrawal for secondary lack of efficacy was stable over 3 to 12 years whereas withdrawal for the mAbs progressively increased over the same period.…”