A steroid-free clinical response had no impact on multiple components of Crohn’s disease progression, based on data from 95 adults.
The therapeutic goals of Crohn’s disease have evolved from controlling symptoms to blocking disease progression and reducing complications, wrote David Laharie, MD, of Hôpital Haut-Lévêque, Pessac, France, and colleagues. The goal of steroid-free remission has been used as an endpoint of treatment, but data on the impact of such remission on long-term disease are limited, the researchers noted in a retrospective study published in Clinical Gastroenterology and Hepatology.
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In the study, the researchers reviewed data from 95 adults with early Crohn’s disease (CD) who participated in the TAILORIX trial involving treatment with infliximab and immunosuppressants. The primary endpoint of the TAILORIX trial was sustained corticosteroid-free remission from week 22 to 54. In the current study, the primary endpoint was progression-free survival at 1, 3, and 5 years in patients who did or did not meet the TAILORIX primary endpoint. The median disease duration was 4.5 months, and the median follow-up was 64.2 months.
Progression-free survival was defined as a composite of luminal surgery, anal surgery, hospitalization, and the need for a new CD treatment during the follow-up period.
In the study population, 45 patients achieved corticosteroid-free remission and 50 did not. At 54 weeks, 17 patients with corticosteroid-free remission (38%) and 28 patients without remission (56%) achieved complete mucosal healing, and progression-free survival rates were similar between these groups.
Overall, the rates of progression-free survival at 1, 3, and 5 years were not significantly different between the remission and nonremission groups: 86% versus 91%, respectively, at 1 year; 70% for both groups at 3 years; and 64% and 61%, respectively, at 5 years.
The researchers also compared individual components of the primary endpoint (luminal surgery, anal surgery, hospitalization, and the need for a new CD treatment), and found no significant differences in survival rates in patients who had and had not achieved steroid-free remission.
Survival rates without luminal surgery at 1, 3, and 5 years were 97% versus 96%, 93% versus 90%, and 87% versus 82%, respectively, for remission and nonremission groups. Similarly, survival rates without anal surgery were 93%, 86%, and 86% versus 96%, 88%, and 85%, respectively, for the two groups. Rates of hospitalization-free survival at 1, 3, and 5 years were 90% versus 92%, 81% versus 81%, and 78% versus 69%, respectively, in the remission and nonremission groups. Survival rates without a new systemic CD treatment also were similar at 1, 3, and 5 years: 93% versus 95%, 71% versus 93%, and 60% versus 51%, respectively, for the remission and nonremission groups.
CD progression was not associated with not achieving corticosteroid-free remission (hazard ratio, 0.861). Other factors that were not associated with disease progression in this study included CRP greater than 5 mg/L, age older than 30 years, active smoking, and B1 phenotype.
The researchers noted that, although endoscopic and clinical remission is currently recommended for CD, “there is no validated or standardized definition of this endoscopic goal.” The high rates of survival without major abdominal surgery, regardless of remission status, suggest a significant impact of early combination therapy for CD patients who were biologic naive. Other studies have shown similar improved outcomes for CD patients with early treatment.
The study findings were limited by several factors including the retrospective design and lack of power to compare long-term progression-free survival, the researchers noted. However, the results were strengthened by the robust data on hospitalizations and surgeries from the TAILORIX trial.
The results support a more flexible strategy for CD, “recommending endoscopic and clinical remission in early diagnosed patients and less stringent objectives in those with more refractory or advanced disease,” they concluded.
Findings may guide patient management
The current study is important to help clinicians know whether CD patients who achieve a short-term, steroid-free clinical and endoscopic remission go on to experience better long-term disease outcomes than those who do not achieve this short-term remission, Atsushi Sakuraba, MD, of the University of Chicago said in an interview.
Dr. Sakuraba said that he was surprised by the study findings. “Achieving a clinical remission off steroids with complete endoscopic remission, i.e., deep remission, is considered a treatment goal, but the fact that it did not result in less disease progression was surprising.”
The take-home message for clinicians from the study is that CD patients may still experience disease progression after achieving a single time of clinical and endoscopic remission “mainly due to loss of response to infliximab, so continued long-term disease monitoring and control are required,” Dr. Sakuraba said.
The current study was a post hoc follow-up analysis of a previous trial, Dr. Sakuraba noted. Therefore, studies primarily focused on changing the disease progression and natural course of CD are warranted.
Dr. Laharie disclosed counseling, boards, transportation, or fees from AbbVie, Biogaran, Biogen, Ferring, HAC-pharma, Janssen, MSD, Novartis, Pfizer, Prometheus, Roche, Takeda, Theradiag, and Tillots. Dr. Sakuraba had no relevant financial conflicts to disclose.