Impact Of Anti-Tnf-Alpha Treatment Failure Complicating Long-Term Maintenance Therapy For Crohn'S Disease

Purpose: Although long-term anti-TNF-α therapy has emerged as the mainstay of treatment for refractory moderate to severe Crohn's disease (CD), a significant subgroup of patients discontinue treatment due to immunogenicity and/or loss of efficacy. Clinical outcome of CD patients who discontinue long-term biologic maintenance treatment with infliximab (IFX) has not been well defined. Methods: This was a retrospective observational cohort analysis of CD pts who had received long-term, scheduled maintenance IFX for > 1 year, but subsequently discontinued therapy. All patients were followed at a single tertiary referral IBD Center between 1998–2007. Our primary outcomes were health related quality of life (QOL) measured using the short inflammatory bowel disease questionnaire (SIBDQ), hospitalizations, surgeries and permanent work disability. We analyzed patterns of IFX dose intensification prior to discontinuation, concomitant immunomodulator use and subsequent forms of therapy. Results: Among153 CD patients who received maintenance IFX treatment beyond 1 year, 42 patients (27%) discontinued treatment. CD patients who failed long-term IFX had a mean age of 39 ± 13 y; a mean disease duration of 15 ± 14.5 yrs; and had a slight female predominance (57%). Prior to discontinuation, 57% of patients (24/42) required IFX dose escalation. 64% of patients failing IFX (27/42) were started on adalimumab (ADA), among whom 22% (6/27) failed the second anti-TNF-α agent. 66% of pts who continued on ADA were maintained on concomitant immunomodulators (IMM). Among IFX long-term failures, 24% of patients received subsequent IMM monotherapy, and 12% were on no specific CD therapy. Following IFX failure, mean SIBDQ scores were similar between patients on IMM monotherapy (41.5 ± 13) or ADA maintenance (42.5 ± 13). CD patients failing a second anti-TNF-α had significantly lower SIBDQ scores (28.8 ± 13) (P < .05). Among the 27 ADA treated patients, there were 39 surgeries and 47 hospitalizations prior to therapy. The 21 ADA responders had a mean of 0.1 hospitalizations (N = 2) per patient and 0 surgeries (N = 0) during follow-up compared to corresponding means of 1.7 and 0.7 among those who failed the second anti-TNF-α agent. Among all long-term IFX failures, permanent disability was seen in 21% (9/42). Conclusion: Long-term anti-TNF-α failures in CD have low QOL and high rates of permanent disability. Patients who respond to a second anti-TNF-α agent have better QOL and lower health care utilization compared with the subgroup of patients who have failed a second anti-TNF-α biologic.