Volume 48, Issue 7, August–September 2025, 502372Author links open overlay panel, , , , , , AbstractObjectives

Moderate to severe Crohn's disease (CD) treatment was revolutionized by introducing anti-tumor necrosis factor (TNF) agents, which is still a cornerstone of the treatment. It is speculated that adipose tissue may influence treatment response, especially for non-weight-adjusted agents.

Patients and methods

Research comparing the effectiveness of anti-TNFs between eutrophic and overweight patients may impact clinical management. We performed a retrospective analysis of a CD patient database. The primary endpoint was loss of response (LOR) after 54 weeks with infliximab (IFX) and adalimumab (ADA) in patients with body mass index (BMI) <25 and ≥25. Secondary endpoints were steroid-free remission and endoscopic remission rate.

Results

One hundred seventy-nine CD patients were evaluated; 48.9% had LOR after 54 weeks of anti-TNF therapy. Fifty-four patients had a BMI ≥25, with 51 receiving IFX and 28 receiving ADA. The univariate analysis identified LOR in 56.5% of the patients with IFX and 34.9% in the ADA group (p = 0.009). In the 54-week multivariate analysis, loss of response in the IFX group with BMI ≥25 had a relative risk of 1.04 [CI 0.60–1.80 (p = 0.891)] compared to patients with BMI <25. Being overweight or obese led to a risk of 1.50 for LOR for ADA at 54-week time point [CI 0.60–3.74 (p = 0.0387)]. Clinical remission at 54 weeks was similar between BMI groups.

Conclusions

Being overweight did not influence the LOR to treatment when IFX and ADA were compared, nor did it affect clinical and endoscopic remission after 54 weeks.

ResumenAntecedentes

El tratamiento de la enfermedad de Crohn (EC) fue revolucionado por los agentes antifactor de necrosis tumoral (TNF) y estos agentes siguen siendo una piedra angular del tratamiento. Se especula que el tejido adiposo puede influir en la respuesta al tratamiento, especialmente para agentes no ajustados al peso. Las investigaciones que comparan la eficacia de los anti-TNF entre pacientes eutróficos y con sobrepeso pueden afectar el manejo clínico.

Métodos

Realizamos un análisis retrospectivo de una base de datos de pacientes con EC. El criterio de valoración principal fue la pérdida de respuesta (LOR) después de 54 semanas con infliximab (IFX) y adalimumab (ADA) en pacientes con IMC (índice de masa corporal) < 25 y ≥ 25. Los criterios de valoración secundarios fueron la remisión clínica sin esteroides y la tasa de remission endoscópica.

Resultados

Se evaluaron un total de 179 pacientes con EC; El 48.9% tuvo LOR después de 54 semanas de terapia anti-TNF. En total, 79 pacientes tenían un IMC ≥ 25, 51 recibieron IFX y 28 recibieron ADA. En el análisis univariado, se identificó LOR en el 56.5% de los pacientes con IFX y en el 34,9% en el grupo ADA (p = 0,009). En el análisis multivariado de 54 semanas, la perdida de respuesta en el grupo IFX con IMC ≥ 25 tuvo un riesgo relativo (RR) de 1.04 [CI 0,60-1.80 (p = 0.891)] em comparación con los pacientes con IMC < 25. El sobrepeso e la obesidad generó un riesgo de 1,50 para LOR para ADA al cabo de 54 semanas [CI 0,60-3,74 (p = 0.0387)]. La remisión clínica a las 54 semanas fue similar entre los grupos de IMC.

Conclusiones

El sobrepeso no influyó en la LOR al tratamiento cuando se compararon IFX y ADA, ni influyó en la remisión clínica y endoscópica después de 54 semanas de tratamiento.

Introduction

The treatment of moderate to severe Crohn's disease (CD) was revolutionized by introducing anti-tumor necrosis factor (TNF) agents, which is still a cornerstone of the treatment. TNF-alpha is a proinflammatory cytokine that plays a vital role in the pathogenesis of CD.1, 2 The most used anti-TNF monoclonal antibodies are infliximab (IFX) and adalimumab (ADA). The chimeric IgG1 monoclonal antibody, IFX, recognizes soluble and membrane TNF-α and neutralizes its biological activity by blocking it from binding with specific receptors. The medication is intravenously administered according to patient weight, with a predominant distribution in the vascular compartment, with a half-life between 8 and 10 days. In most patients, IFX can be detected in serum for at least 8 weeks after a 5 mg/kg dose.3 Conversely, ADA is a recombinant human anti-TNF antibody IgG1, binding with high affinity and specificity to human soluble TNF.4 It is subcutaneously administered with a fixed dosage, independently of patient weight. The absorption and distribution of ADA are slower and more progressive, with peak concentrations up to five days after subcutaneous administration. Its mean half-life is approximately two weeks, varying from 10 to 20 days between different studies.4 Despite the critical role of anti-TNF agents in treating CD, loss of response (LOR) to these agents is a frequent problem for physicians in clinical practice. LOR occurs in approximately 40% of patients in the first year of therapy and has an annual incidence of approximately 13% for IFX.5 Approximately 40% of patients receiving ADA need dose adjustment for maintenance of clinical remission, with a LOR of approximately 20% per patient-year.6

The presence of a higher concentration of adipose tissue may influence the response to treatment, especially for medications that are not weight dependent. Pharmacokinetic studies with anti-TNF agents identified higher body mass index (BMI) as a risk factor associated with increased drug clearance, shorter half-life, and lower drug concentrations.7, 8, 9, 10 Research evaluating variation in the effectiveness of anti-TNF agents between eutrophic and overweight or obese patients is warranted, as this can directly impact clinical management. The present study aimed to compare loss of response (LOR) rates between patients with a BMI <25 and ≥25 after 54 weeks of therapy with IFX and ADA. We also aimed to determine whether BMI predicted loss of clinical and endoscopic response in patients using IFX and ADA for CD.

Section snippetsStudy design and patient selection

A retrospective analysis from a prospectively maintained database was conducted, including patients with CD who attended the outpatient IBD clinics from a large tertiary hospital in south Brazil for 9 years. Patients with a confirmed diagnosis of CD for at least 6 months were included based on current clinical, radiographic, endoscopic, and histological criteria. Two senior trained physicians interviewed the patients and reviewed medical records using a standardized data collection instrument.

Patient population

Initially, 191 CD patients were identified. Twelve patients were excluded due to loss of follow-up and missing data. Table 1 demonstrates the demographic data and baseline characteristics of the 179 patients included in the final analysis. The median age at diagnosis was 28 years, and 28.7% had stricturing disease, 40.8% of patients had a BMI ≥25 kg/m2. The median BMI across all participants was 24.3 kg/m2.

Loss of response

Overall, 48.9% of the patients presented LOR at a follow-up period of 54 weeks after

Discussion

Obesity has increased worldwide, and IBD has shown a similar trend. Previous studies have reported that 15%–40% of IBD patients are obese and 20%–40% are overweight.13, 14, 15, 16 This reality is valid for the Brazilian population as well. According to the Brazilian Ministry of Health, more than 50% of the Brazilian population suffers from being overweight and obese.17, 18

It is known that IBD patients with high BMI are more prone to developing perianal and penetrating disease and have higher

Conflict of interests

The authors state that they have no conflict of interests.

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