Clinical and Pharmacokinetic Factors Associated With Adalimumab-Induced Mucosal Healing in Patients With Crohn’s Disease

Abstract

In a post hoc analysis of data from a randomized controlled trial of patients with moderate to severe CD, we found that adalimumab in combination with azathioprine increased trough levels of adalimumab. Higher trough levels of adalimumab associated with endoscopic response and mucosal healing at Weeks 26 and 52. UMIN registration No: 000005146.

Impact of immunomodulator use on treatment persistence in patients with ulcerative colitis: A claims database analysis

“…Our study therefore demonstrates the superiority of "step-up" infliximab over "stepup" adalimumab in terms of persistence for patients who were already prescribed an IM. 12,14,[19][20][21][22] There was no significant impact of combination treatment on persistence in the Bio + IM subgroup in either the infliximab or the adalimumab analysis; the lack of effect on persistence in infliximab-prescribed patients in the Bio + IM subgroup implies that persistence is likely to be high when infliximab is added to an existing IM. As the analysis focused on persistence during maintenance in patients who had completed the induction phase of biologic therapy without switching or discontinuing treatment, differences in the duration of induction between the two biologics were not considered to be relevant.…”

“…In addition to SUCCESS in UC, 13 the SONIC and DIA-MOND studies investigated infliximab and adalimumab treatment, respectively, in patients with CD. [18][19][20][21][22] Combination treatment with a biologic and an IM was started simultaneously in all three studies, 13,[18][19][20][21][22] whereas in the real-world setting, many UC patients may receive an IM prior to starting biologic therapy and may already be failing to respond to treatment. 6,24 In such cases, physicians may not have adequate information on previous treatments to make an informed decision as to which biologic to prescribe (infliximab or adalimumab) or whether to continue longterm (potentially failing) IM treatment when initiating anti-TNFα therapy; these decisions must therefore be made on a case-by-case basis.…”

“…6 As such, in daily practice, anti-TNFα therapies are often prescribed to patients already on an IM, as part of a "step-up" treatment approach. 16,17 Furthermore, previous combination studies, such as SUCCESS (in UC patients) and SONIC and DIAMOND (both in CD patients), only investigated the efficacy of anti-TNFα agents during the induction phase of treatment, where treatment duration range was 16-30 weeks; 13,[18][19][20][21][22] consequently, long-term outcomes data for these agents, when used as both induction and maintenance treatment, are not available. [11][12][13][14][15] Data collected so far have been contradictory; some studies have reported a benefit in terms of UC remission for combination treatment using anti-TNFα agents with IMs, while others have reported no effect compared with monotherapy.…”

“…In fact, the absence of benefit from a concomitant IM in a step-up approach for Crohn's disease (CD) has been shown previously. 16,17 Furthermore, previous combination studies, such as SUCCESS (in UC patients) and SONIC and DIAMOND (both in CD patients), only investigated the efficacy of anti-TNFα agents during the induction phase of treatment, where treatment duration range was 16-30 weeks; 13,[18][19][20][21][22] consequently, long-term outcomes data for these agents, when used as both induction and maintenance treatment, are not available.…”

Maintenance Adalimumab Concentrations Are Associated with Biochemical, Endoscopic, and Histologic Remission in Inflammatory Bowel Disease

“…Previous studies, typically referring to CD and using ELISA as the TDM assay, demonstrated that maintenance adalimumab concentration thresholds of 5.6–6.6 μg/ml and 4.9–10.3 μg/ml were associated with CRP normalization and mucosal healing, respectively. 6, 8, 11–18, 23 Yarur et al showed that the adalimumab concentration that was best associated with histologic healing in patients with IBD was 7.8 μg/ml. 7 Ungar et al identified an adalimumab therapeutic drug window of 8–12 μg/mL as being associated with a mucosal healing rate of 80–90%.…”