Introduction
Tumor necrosis factor (TNF) inhibitor therapies (anti-TNFs) are routinely used for the management of Crohn’s disease (CD) in patients with moderate to severe disease activity. However, approximately 30% of patients discontinue anti-TNF treatment due to inefficacy or adverse events.
Aims & Methods
This study analyzed the long-term anti-TNFα drug survival in a cohort of patients with CD from central Greece aiming to find potential predictive factors that are associated with increased survival of anti-TNF agents. All adult patients with CD treated with anti-TNF agents including infliximab (IFX) ή adalimumab (ADA) from 2012 to 2022 in the sole tertiary referral center for inflammatory bowel disease in central Greece were screened for eligibility and their electronic medical records were reviewed retrospectively. Data collected included the socio-demographic and clinical characteristics of our population as well as specific information regarding anti-TNF treatment survival, concomitant treatment modalities, treatment compliance, adverse events, and the need for treatment optimization. Parametric and non-parametric statistical tests were used for the description of the study population. To evaluate the survival of anti-TNF agents, a Kaplan-Meier survival curve was performed whereas the influence of population characteristics on the survival of anti-TNF agents was assessed with linear regression. Patients with incomplete data were excluded from the analysis.
Results
193 patients were screened for eligibility and 123 were finally included. Over the study period, 68% and 71% of the population treated with IFX and ADA required treatment optimization. The majority of the population (>60%) received anti-TNF as a 1-st line treatment. At 1 year, the probability of retaining anti-TNFs was>75% with no significant differences being recorded between IFX and ADA whereas the percentage of patients who remained on the same treatment at 5 years gradually reduced to 23% and 35% respectively. Among the population characteristics, the increased disease duration at the onset of treatment was the sole factor that was positively associated with increased survival to both anti-TNFs ([standardized beta: .545, t: 3.690, p: < .001 95,0% Confidence Interval: 1.580-5.511 for ADA], [ standardized beta: .479, t:5.119, p: <.001 95,0% Confidence Interval: 1.738-3.952 for IFX]), whereas the development of antibodies ( standardized beta: .247, t: 2.639, p: < .01 95,0% Confidence Interval: 3.682-26.312) and the early need for treatment optimization (standardized beta: .203, t: 2.128, p: < .037 95,0% Confidence Interval: 1.373-41.358), defined as the need for treatment optimization within the first year, were the sole factors that were associated with reduced survival of IFX.
Conclusion
Treatment survival with anti-TNF agents decreases in CD patients over time. A trend for increased long-term survival was recorded for ADA over IFX. Among CD patients, the increased disease duration at treatment onset was found to be associated with increased treatment survival irrespective of the type of anti-TNF agents that was selected. Immunogenicity and the need for early treatment optimization were the sole factors that were associated with reduced treatment survival among CD patients receiving IFX.
References
Torres J, Bonovas S, Doherty G, Kucharzik T, Gisbert JP, Raine T, Adamina M, Armuzzi A, Bachmann O, Bager P, Biancone L, Bokemeyer B, Bossuyt P, Burisch J, Collins P, El-Hussuna A, Ellul P, Frei-Lanter C, Furfaro F, Gingert C, Gionchetti P, Gomollon F, González-Lorenzo M, Gordon H, Hlavaty T, Juillerat P, Katsanos K, Kopylov U, Krustins E, Lytras T, Maaser C, Magro F, Marshall JK, Myrelid P, Pellino G, Rosa I, Sabino J, Savarino E, Spinelli A, Stassen L, Uzzan M, Vavricka S, Verstockt B, Warusavitarne J, Zmora O, Fiorino G. ECCO Guidelines on Therapeutics in Crohn's Disease: Medical Treatment. J Crohns Colitis. 2020 Jan 1;14(1):4-22. doi: 10.1093/ecco-jcc/jjz180. PMID: 31711158.
