Switching TNFα inhibitors: Patterns and determinants

Abstract

The aim of this study was to assess switching patterns and determinants for switching in patients initiating TNFα inhibitor (TNFα-i) treatment. Patients were included who started TNFα-i treatment between July 1, 2012 and December 31, 2017, from three Dutch hospitals, and were diagnosed with rheumatic diseases (RD), inflammatory bowel disease (IBD), or psoriasis. Outcomes were switching, defined as initiating another biological; switching patterns including multiple switches until the end of follow-up; determinants for first switch, assessed using multivariate logistic regression. A total of 2228 patients were included (median age 43.3 years, 57% female), of which 52% (n = 1155) received TNFα-i for RD, 43% (n = 967) for IBD, and 5% (n = 106) for psoriasis. About 16.6% of RD patients, 14.5% of IBD patients, and 16.0% of psoriasis patients switched at least once, mainly to another TNFα-i. TNFα-i dose escalation (OR 13.78, 95% CI 1.40-135.0) and high-dose corticosteroids initiation (OR 3.62, 95% CI 1.10-12.15) were determinants for switching in RD patients. TNFα-i dose escalation (OR 8.22, 95% CI 3.76-17.93), immunomodulator initiation/dose escalation (OR 2.13, 95% CI 1.04-4.34), high-dose corticosteroids initiation (OR 6.91, 95% CI 2.81-17.01) and serum concentration measurement (OR 5.44, 95% CI 2.74-10.79) were determinants for switching in IBD patients. Switching biological treatment occurred in about one in six patients. RD patients with TNFα-i dose escalation and/or high-dose corticosteroids initiation were more likely to switch. IBD patients with TNFα-i or immunomodulator initiation/dose escalation, high-dose corticosteroids initiation or serum concentration measurement were more likely to switch. These findings might help clinicians anticipating switching in TNFα-i treatment.

Keywords: biological products; drug utilization; inflammatory bowel diseases; pharmacoepidemiology; rheumatology; tumor necrosis factor inhibitors.

FIGURE 1

Kaplan–Meier curve of time of persistent use of initial TNFα inhibitor; time until switch to another biological; time until discontinuation TNFα inhibitor without switching for all indications (A), RD (B), IBD (C) and psoriasis (D)

FIGURE 2

(A) Switching patterns of RD patients with median time (IQR) until switch. TNFα inhibitors (etanercept, infliximab, adalimumab, certolizumab, golimumab) were colored purple, selective immunosuppressants (abatacept, tofacitinib, baricitinib) were colored red, interleukin inhibitors (anakinra, ustekinumab, tocilizumab, secukinumab) were colored green and rituximab was colored yellow. (B) Switching patterns of IBD patients with median time until switch. TNFα inhibitors (infliximab, adalimumab, golimumab) were colored purple, selective immunosuppressants (vedolizumab) were colored red and interleukin inhibitors (anakinra, ustekinumab) were colored green. (C) Switching patterns of psoriasis patients with median time until switch. TNFα inhibitors (etanercept, infliximab, adalimumab) were colored purple and interleukin inhibitors (ustekinumab, secukinumab) were colored green