Combination Therapy of Adalimumab With an Immunomodulator Is Not More Effective Than Adalimumab Monotherapy in Children With Crohn’s Disease: A Post Hoc Analysis of the PAILOT Randomized Controlled Trial

Abstract

Background The PAILOT trial was a randomized controlled trial aimed to evaluate proactive vs reactive therapeutic drug monitoring in children with Crohn’s disease (CD) treated with adalimumab. Our aim in this post hoc analysis of the PAILOT trial was to assess the efficacy and safety of adalimumab combination treatment in comparison with monotherapy at week 72 after adalimumab induction. Methods Participants were children 6–17 years old, biologic naïve, with moderate to severe CD, who responded to adalimumab induction at week 4. Patients receiving immunomodulators at baseline maintained a stable dose until week 24; patients could then discontinue immunomodulators. At each visit, patients were assessed for disease index, serum biomarkers, fecal calprotectin, adalimumab trough concentration, and anti-adalimumab antibodies. Results Out of the 78 patients (29% female; mean age, 14.3 ± 2.6 years), 34 patients (44%) received combination therapy. During the study period, there was no significant difference in the rates of sustained corticosteroid-free clinical remission (25/34, 73%, vs 28/44, 63%; P = 0.35) or sustained composite outcome of clinical remission, C-reactive protein ≤0.5 mg/dL, and calprotectin ≤150 µg/g (10/34, 29%, vs 14/44, 32%; P = 0.77) between the combination group and the monotherapy group, respectively. Clinical and biological outcomes did not differ between the proactive and reactive subgroups within the combination and monotherapy groups. Adalimumab trough concentrations and immunogenicity were not significantly different between groups. The rate of serious adverse events was not significantly different between groups but was numerically higher in the monotherapy group. Conclusions Combination therapy of adalimumab and an immunomodulator was not more effective than adalimumab monotherapy in children with CD (ClinicalTrials.gov No. NCT02256462).

Factors Associated with the Immunogenicity of Anti-Tumor Necrosis Factor Agents in Pediatric Patients with Inflammatory Bowel Disease

“…9 There is limited data regarding the immunogenicity to ADL from studies on children with IBD. ADAs to ADL have been re-ported to occur in 3.3% to 10.3% of pediatric patients, 21,22 which is a relatively lower proportion than that observed among their counterparts receiving IFX and also among adult patients with IBD. The absence of ADAs against ADL observed in our study could be due to the significantly shorter duration of anti-TNF treatment in patients treated with ADL compared with those receiving IFX (0.9±0.5 years vs 3.0±1.3 years; p<0.001).…”

“…Meanwhile, a recent study of children with CD revealed that there was no benefit of adding an immunomodulator to ADL treatment compared with ADL monotherapy. 22 Further large-scale and longitudinal studies on the impact of concomitant treatment with an immunomodulator during treatment with ADL in children are required for better insight. Therapeutic drug monitoring (TDM) of anti-TNF agents has emerged as a strategy to optimize and personalize treatment based on measurement of TLs and ADAs.…”

Therapeutic Monitoring of Adalimumab at Non-Trough Levels to Gauge Its Efficacy in Patients with Inflammatory Bowel Disease in Clinical Practice

“…Reports on the bene ts of the combined use of immunomodulators with ADA are controversial [19][20][21][22][23][24]. Although there was no association between the concomitant use of immunomodulators with ADA versus only ADA in this study (P = 0.252), we found that AAA positivity was signi cantly lower in the immunomodulator combination group (1/27 [3.7%] vs. 11/25 [44%], P < 0.05, Mann-Whitney's U-test).…”

Therapeutic monitoring of adalimumab at non-trough levels in patients with inflammatory bowel disease

“…Reports on the benefits of the combined use of immunomodulators with ADA are controversial [19][20][21][22][23][24]. In this study, although there was no association between the concomitant use of immunomodulators with ADA and only ADA (P = 0.252), AAA positivity was significantly lower in the immunomodulator combination group than in the immunomodulator non-combination group (1/27 [3.7%] vs. 11/25 [44%], P <0.05, Mann-Whitney U test).…”