Impact of biologic agents with and without concomitant methotrexate and at reduced doses in older rheumatoid arthritis patients

Abstract

Objective: To examine whether concomitant methotrexate (MTX) use is associated with better biologic persistence and whether self-administered anti-tumor necrosis factor (anti-TNF) therapies are used at reduced doses in real-world clinical care settings, not just clinical trials.

Methods: We conducted a retrospective cohort study among rheumatoid arthritis (RA) patients using Medicare claims data from 2006 to 2012. Subjects were new initiators of etanercept, infliximab, adalimumab, abatacept, and tocilizumab with at least 12 months of continuous medical and pharmacy coverage after treatment initiation. We examined the association between concomitant MTX use and persistence on biologic agents using Cox proportional hazards regression, adjusting for demographics and baseline comorbidities. We further identified a subgroup of patients who initiated and were adherent on etanercept or adalimumab for at least 12 months and examined the proportion of patients who subsequently used these therapies at reduced doses continuously for an additional 12, 18, and 24 months.

Results: Of 26,510 eligible RA patients, 10,511 initiated biologic monotherapy. Overall, patients who initiated biologic monotherapy were 1.4 (95% confidence interval [95% CI] 1.3-1.5) times more likely to discontinue at 1 year compared to those who initiated combination therapy, and 1.8 (95% CI 1.7-2.0) times more likely if starting infliximab monotherapy. Approximately 10-20% of patients who initiated and adhered to etanercept and adalimumab for ≥12 months subsequently received reduced-dose therapy for an 12 additional months and beyond.

Conclusion: In real-world practice, concomitant MTX was associated with improved persistence on biologic therapy, especially for infliximab users; reduced-dose injectable anti-TNF therapy was used by a substantial proportion of RA patients.

Figure 1

Kaplan-Meier plot of time to discontinuation by type of biologic therapy and use of concomitant methotrexate

Figure 2

a. Proportion of RA Patients Who Continuously Used Reduced Dose Injectable Etanercept or Adalimumab By Length of Follow-up (<80% days covered) a presents data among adherent patient defined as having PDC≥80% for the first 12 months since biologic initiation. Follow-up started on Month 13 and each bar represents the proportion of patients who continuously used reduced dose biologic (PDC < 80%). Results were stratified into the 3 bar graphs based upon the length of follow-up time during which the patients must have remained persistent with therapy. b. Proportion of RA Patients Who Continuously Used Reduced Dose Injectable Etanercept or Adalimumab using Alternative Definition (<70% days covered) b presents data among adherent patient defined as having PDC≥70% for the first 12 months since biologic initiation. Follow-up started on Month 13 and each bar represents the proportion of patients who continuously used reduced dose biologic using an alternative definition (PDC < 70%). Results were stratified into the 3 bar graphs based upon the length of follow-up time during which the patients must have remained persistent with therapy.

Figure 2

a. Proportion of RA Patients Who Continuously Used Reduced Dose Injectable Etanercept or Adalimumab By Length of Follow-up (<80% days covered) a presents data among adherent patient defined as having PDC≥80% for the first 12 months since biologic initiation. Follow-up started on Month 13 and each bar represents the proportion of patients who continuously used reduced dose biologic (PDC < 80%). Results were stratified into the 3 bar graphs based upon the length of follow-up time during which the patients must have remained persistent with therapy. b. Proportion of RA Patients Who Continuously Used Reduced Dose Injectable Etanercept or Adalimumab using Alternative Definition (<70% days covered) b presents data among adherent patient defined as having PDC≥70% for the first 12 months since biologic initiation. Follow-up started on Month 13 and each bar represents the proportion of patients who continuously used reduced dose biologic using an alternative definition (PDC < 70%). Results were stratified into the 3 bar graphs based upon the length of follow-up time during which the patients must have remained persistent with therapy.