Efficacy of Adalimumab as first-line “top-down” therapy in pediatric Crohn's Disease: 12 months of follow-up

Objectives and Study: Anti-tumour necrosis factor (TNF) agents are highly efficient in inducing and maintaining remission in pediatric Crohn's disease (CD). The question is who is the right patient and when is the right moment to introduce anti-TNF medication. Recent ECCO-ESPGHAN guidelines indicate a clear place of anti-TNF biologics in patients with positive predictors of poor outcome. The aim of our study was to evaluate the efficacy of adalimumab (ADA) as first-line therapy by comparing two НiffОrОnt stratОgiОsŚ χDχ “top Нown” in immunomoНulator anН anti-TNF naïve CD patients versus a “stОp up” stratОgy in patiОnts rОМОiving immunosupprОssivО agОnts (thiopurinО anН/or infliximabΨ before ADA. Method: Patients followed for CD at Necker hospital that started their ADA therapy between 2005 and 2017 were retrospectively reviewed. The beginning of the study (M0) was the date of first ADA injection. Enrolled patients were divided into 2 groups according to the treatment strategy. Group A was composed of patients naïve of immunosuppressors and anti TNF agents who started early ADA aftОr inНuМtion of rОmission, rОsulting in a “top Нown” stratОgy whilО group ψ was МomposОН by patiОnts who startОН χDχ aftОr a morО МlassiМal stratОgy (iО “stОp up” stratОgy using immunosuppressive agents then infliximab). For each patient were collected data at M0, M3, M6, M9 and M12 regarding the disease activity score (wPCDAI), auxological parameters, biological parameters (CRP, ESR, Albumin, ADA trough levels and antibodies anti-ADA). Results: 83 patients (43 boys) were enrolled in the study, 43,3% (n=36) in group A and 56,6% (n=47) in group B. Mean age at the start of ADA was 13.6 ± 2.6 years. At inclusion the 2 groups were comparable with a mean wPCDAi of 40.75 ± 14,8 in group A versus 45.6 ± 15,5 in group B. At 6 months, the 2 groups were in clinical remission with a median wPCDAI of 0 (0-12.5 IQR) in group A (n = 30) versus 0 (0-7.5 IQR) in group B (n=38) (p: 0.509). CRP level decreased from 15.5 (4.7-35.8 IQR) to 1.1 (0.5-5.6 IQR) in group A vs 17.1 (6.5-37.7 IQR) to 4,8 (0.7-6.1 IQR) in group B (p: 0.945 e p: 0.086). For the subgroup of patients who reached the 1 year follow up, there were no significant differences regarding the mean wPCDAI, CRP, ESR and serum allbumin between the 2 groups. Conclusion: ThО prОsОnt stuНy НОmonstratОs that thО “top Нown” stratОgy using Оarly χDχ monotherapy in disease course is as effective as a step-up strategy. Moreover, ADA monotherapy is as effective as combotherapy in maintaining clinical and biological remission at 1 year of follow-up in paediatric CD patients. Those results are very important to identify the best strategy in pediatric CD patients, where safety concerns are major.