adalimumab (Mabura)

Outcomes of adalimumab biosimilar nonmedical switches in children and young adults with inflammatory bowel disease.

Himelstein Daniel D, McNicol Megan M, Abdel-Rasoul Mahmoud M, Boyle Brendan M BM et al.

Adalimumab biosimilars are as safe and effective compared to the originator. Adult patients with inflammatory bowel disease (IBD) who switched to a biosimilar have comparable outcomes, but pediatric data are limited. This study evaluates clinical outcomes of children and young adults with IBD following a nonmedical, insurance-driven switch from the adalimumab originator to a biosimilar. A single-center retrospective chart review was conducted among pediatric and young adult patients with IBD who switched from the adalimumab originator to a biosimilar between May 2023 and July 2024. Demographics, Physician Global Assessment (PGA), laboratory values, adalimumab levels, and antibodies were collected preswitch and up to 6 months postswitch. Adalimumab biosimilar continuation was assessed 6 months postswitch. McNemar's exact test, linear mixed effect models, and paired t-tests compared variables preswitch and postswitch. Fifty patients switched to a biosimilar. Forty-two patients had PGAs pre and postswitch, and among them, 86% (36/42) of patients demonstrated stable or improved PGAs postwitch. Seventy-six percent (38/50) of patients continued on the biosimilar for at least 6 months postswitch. Of the 12 patients who discontinued adalimumab biosimilar, 42% (5/12) discontinuation was not related to the switch, while 58% (7/12) were due to the switch. Laboratory values remained stable pre and postswitch, although adalimumab levels decreased postswitch (18-15 µg/mL; p = 0.007). Switching from the adalimumab originator to a biosimilar resulted in comparable outcomes in children and young adults with IBD based on PGA, laboratory markers, and continuation of the medication.

The influence of symptom duration on flare risk after biologic DMARD withdrawal in axial spondyloarthritis: a meta-analysis of randomized withdrawal trials.

Benavent Diego D, Navarro-Compán Victoria V, Capelusnik Dafne D, Ramiro Sofia S

To assess whether symptom duration modifies flare risk after biologic/targeted synthetic DMARD (b/ts DMARDs) withdrawal in axial spondyloarthritis (axSpA) following remission/inactive disease. We systematically identified randomized placebo-controlled trials evaluating withdrawal or tapering of b/tsDMARDs in axSpA through a previous systematic literature review. Eligible studies included adults with axSpA who achieved inactive disease or remission by ASDAS and were randomized to continuation or withdrawal/tapering, with available flare data. Patient-level data were obtained from Vivli and stratified by symptom duration thresholds of ≤2, 3, 4, or 5 years. Relative risks (RRs) of flare for continuation versus withdrawal were calculated within each subgroup, and relative risk ratios (RRRs) were estimated. Random-effects meta-analysis was performed. A subgroup analysis included only patients with nr-axSpA. Three RCTs involving 773 patients were included, evaluating adalimumab, certolizumab pegol, and ixekizumab versus placebo; no tsDMARD or tapering studies were eligible. Continuation of bDMARDs was consistently associated with fewer flares than withdrawal. Symptom duration did not significantly modify flare risk overall. In the overall axSpA population, pooled RRRs showed no statistically significant effect modification: 0.61 (95% CI 0.29-1.28) for ≤2 years, 0.77 (0.54-1.12) for ≤3 years, 0.83 (0.45-1.54) for ≤4 years and 0.82 (0.49-1.37) for ≤5 years. In nr-axSpA (n=508), pooled RRRs favoured shorter symptom duration at ≤4 years (0.25 (0.07-0.96)) but not at ≤2, ≤3 or ≤5 years. Symptom duration did not consistently modify flare risk after bDMARD withdrawal in axSpA overall, although exploratory findings suggest a potential effect in early nr-axSpA.

Reactive Therapeutic Drug Monitoring Guides Optimal Management of Adalimumab Failure in Pediatric Crohn's Disease: A Real-World Single-Center Experience.

Jeong In Sook IS, Kim Tae-Gyeong TG, Yi Dae Yong DY, Kim Kyung Mo KM

Although biologics, including anti-tumor necrosis factor (TNF) drugs, are increasingly used for treating pediatric Crohn's disease (CD), the potential loss of response (LOR) to these drugs requires attention. This retrospective study investigated reactive therapeutic drug monitoring (TDM) and the clinical course of pediatric-onset CD in patients treated with adalimumab. Patients aged <18 years diagnosed with CD and treated with adalimumab were enrolled in this study. Reactive TDM levels, presence of anti-drug antibodies (ADAs), and LOR were evaluated from 2017 to 2019, and clinical outcomes were followed up until June 2022. Thirty-two pediatric patients with CD were enrolled: 14 in the LOR group and 18 in the remission group. The median ages at CD diagnosis and first adalimumab injection were 13 and 14 years, respectively. The median duration of adalimumab injection was 12.5 months. Among 7 patients with therapeutic trough levels (TLs) and undetectable ADAs, 5 achieved clinical remission with continued adalimumab, whereas 2 remained refractory and subsequently switched to alternative biologics. Among 5 patients with subtherapeutic TLs (<5 µg/mL) and undetectable ADAs, 3 eventually underwent a switch to other biologic agents despite interval shortening, while the remaining 2 were ultimately diagnosed with monogenic inflammatory bowel disease (IBD) after further genetic evaluation. Reactive TDM and ADA categorizes the mechanisms of LOR to adalimumab in pediatric CD, guiding appropriate dose escalation or biologic switching. When these strategies fail, exploring underlying monogenic disorders is essential for optimal management.

Extrapulmonary Tuberculosis Despite Preventive Therapy During Adalimumab for Psoriasis.

Torres Tiago T, Luz Martim M