No Benefit of Continuing 5-Aminosalicylates in Patients with Crohn's Disease Treated with Anti-metabolite Therapy

Abstract

Background and aims: 5-aminosalicylates (5-ASA) are frequently used in the management of Crohn's disease (CD). We used a de-identified administrative claims database to compare patterns and outcomes of continuing versus stopping 5-ASA in patients with CD who escalated to anti-metabolite monotherapy.

Methods: Patients with CD on 5-ASA who were new users of anti-metabolite monotherapy and followed for at least 12 months from OptumLabs® Data Warehouse. Three patterns of 5-ASA use were identified: stopped 5-ASA, short-term 5-ASA (use for < 6 months after starting anti-metabolites), or persistent 5-ASA (use for > 6 months after starting anti-metabolites). Outcomes (need for corticosteroids, risk of CD-related hospitalization and/or surgery, treatment escalation to biologic therapy) were compared using Cox proportional hazard analysis adjusting for key covariates, with a 12-month immortal time period.

Results: Of 3036 patients with CD who were new-users of anti-metabolite monotherapy, 667 (21.9%), 626 (20.6%), and 1743 (57.4%) stopped 5-ASA, used 5-ASA transiently or persistently, respectively. Compared to patients who stopped 5-ASA after starting anti-metabolites, persistent 5-ASA use was associated with a higher risk of corticosteroid use (HR, 1.24 [1.08-1.42]), without an increase in risk of CD-related hospitalization (HR, 1.21 [0.98-1.49]), CD-related surgery (HR, 1.28 [0.90-1.80]) or treatment escalation (HR, 0.85 [0.62-1.20]). Sensitivity analyses using a 3-month window after initiation of anti-metabolites to classify patients as continuing vs. stopping 5-ASA showed similar results. Residual confounding by disease severity could not be excluded.

Conclusion: 5-ASAs are frequently continued long-term even after escalation to anti-metabolite therapy in patients with CD but offer no clinical benefit over stopping 5-ASA.

Keywords: Immunosuppressive; Inflammatory bowel diseases; Low-value care; Mesalamine.

Figure 1.

Flow of patients for identification of anti-metabolite-treated patients with Crohn’s disease

Figure 2.

Comparative effectiveness of stopping 5-ASA vs. short-term 5-ASA use vs. persistent 5-ASA use in anti-metabolite-treated patients with Crohn’s disease, 12-month landmark analysis: (A) CD-related hospitalization and/or emergency department visit, (B) CD-related surgery, (C) Flare requiring corticosteroids and (D) Escalation of immunosuppressive therapy.

Figure 2.

Comparative effectiveness of stopping 5-ASA vs. short-term 5-ASA use vs. persistent 5-ASA use in anti-metabolite-treated patients with Crohn’s disease, 12-month landmark analysis: (A) CD-related hospitalization and/or emergency department visit, (B) CD-related surgery, (C) Flare requiring corticosteroids and (D) Escalation of immunosuppressive therapy.

Figure 2.

Comparative effectiveness of stopping 5-ASA vs. short-term 5-ASA use vs. persistent 5-ASA use in anti-metabolite-treated patients with Crohn’s disease, 12-month landmark analysis: (A) CD-related hospitalization and/or emergency department visit, (B) CD-related surgery, (C) Flare requiring corticosteroids and (D) Escalation of immunosuppressive therapy.

Figure 2.

Comparative effectiveness of stopping 5-ASA vs. short-term 5-ASA use vs. persistent 5-ASA use in anti-metabolite-treated patients with Crohn’s disease, 12-month landmark analysis: (A) CD-related hospitalization and/or emergency department visit, (B) CD-related surgery, (C) Flare requiring corticosteroids and (D) Escalation of immunosuppressive therapy.