R Lujan, R Buchuk et al. Gastroenterol 2024; 166: 815-825.Early Initiation of Biologics and Disease Outcomes in Adults and Children With Inflammatory Bowel Diseases: Results From the Epidemiology Group of the Nationwide Israeli Inflammatory Bowel Disease Research Nucleus Cohort
Methods: All patients diagnosed with CD or UC in Israel (2005–2020) were included in the Epidemiology Group of the Israeli Inflammatory Bowel Disease Research Nucleus cohort. The authors compared disease duration at biologics initiation (ie, 0–3 months, >3–12 months, >1–2 years, and >2–3 years) using the cloning, censoring, and weighting by inverse probabilities method to emulate a target trial, adjusting for time-varying confounders and selection bias.
Of the 34,375 included patients (of whom 5240 [15%] were children), 7452 of 19,264 (39%) with CD and 2235 of 15,111 (15%) with UC received biologics. To attempt to adjust for patient characteristics, “essentially, each patient was cloned 4 times and 1 clone was assigend to each treatment strategy at baseline…[they were removed] subsequently if they did not receive the biologic within the acceptable time window.” Key findings:
- In CD, by 10 years postdiagnosis, the probability of CD-related surgery decreased gradually but modestly with earlier initiation of biologics; a significant difference was noted between >2–3 years (31%) and 0–3 months (18%; P = .02; number needed to treat, 7.7)
- In CD, the 10-year probability of steroid dependency for the 0–3-month period (19%) differed both from the >2–3-year (31%; P < .001) and 1–2-year periods (37%; P < .001).
- In UC, no significant differences in colectomy or steroid dependency rates were observed between the treatment initiation periods.
- Similar trends were noted in the pediatric population.
Thus, overall, the study found that early initiation of biologics was associated only with a modest reduced risk of surgery and steroid dependency for Crohn’s disease. It was not found to reduce risk of colectomy or steroid dependency in UC.
My take: In my view, this study probably underestimates the benefits of early biologic therapy. Even though, lead time bias can skew interpretation, inadequately-treated disease likely leads to long-term damage. The associated editorial (pg 728) by Murphy notes that despite the sophisticated statistical methodology, all observational studies cannot fully control for unmeasured confounders.
Related blog posts:
- Is It RISKy Not To Use Anti-TNF Therapy for Pediatric Crohn’s Disease?
- Early Treatment Can Prevent Fistulas in Pediatric Crohn’s Disease
- What is Mild Crohn’s Disease and How to Treat It
- Paris Classification Quiz and Explanation
- CCFA: Updates in Inflammatory Bowel Disease 2017 (part 3)
- Paris Classification of Pediatric Crohn’s Disease
- Validated SEMA-CD Score For Crohn’s Disease
This past weekend there were two fun events in Atlanta -Porchfest (Virginia Highlands) and Midtown Garden Stroll. Porchfest featured more than 50 local bands.
Here’s a couple photos from the Midtown Garden Stroll:
gutsandgrowth 
Dear Dr. Hochman,
I have been reading your emails/blogs for about 6 months now. I find them so informative and you explain issues/studies clearly to lay people like me.
My son, now 28, was diagnosed with Crohn’s at the age of 19, and had a resection the summer of his college sophomore year. He was good for awhile (he has been on Remicaide for almost 10 years every 8 weeks at 10mg/kg). He is still on this but had adhesion surgery this past summer that went wrong/had a complication and had a 2nd surgery 5 weeks later to take out his ICV due to his small intestine flipping on itself due to a hematoma from the first surgery. He is better now but having trouble absorbing iron so we are trying to get to the bottom of this as he does not want to continue to have iron infusions every 6 weeks and he would like to do some long term traveling. Anyway, this is background for what I am about to say and maybe you can address it.
Most likely looking back my son probably had mild Crohn’s symptoms at the age of 16 but our pediatrician did not diagnose it/send us to a GI or even investigate Ted’s shorter stature with a blood test. (He said my husband, 5’9″ and I, 5’4″, were not tall so Ted at 5’6″ was fine, though my brothers are 6 feet and over). Anyway, what I find so perplexing about all these studies that say “get treatment early” is that along the line pediatricians (regular pediatricians not GI pediatricians) need to be more educated in Crohn’s. I think if our pediatrician had taken a blood test (Ted’s inflammation markers were our clue as they were extremely elevated) perhaps we would have been sent to a GI to determine his Crohn’s earlier. What is the medical profession doing to pass down the line to first line pediatricians to help them diagnose IBD? That I think would then get patients on treatment sooner. What do you think? I mean it is fine to say get treatment early, but unless the patient has very severe symptoms, nothing is done.
Thank you for taking the time.
Sincerely,
Bette Fruchtman
I am sorry your son has had to to have multiple surgeries/complications.
I am glad that some of the blog posts (which are mainly geared for medical professionals) are helpful.
In terms of earlier diagnosis, many pediatric GIs give frequent lectures (at all stages of training) to help pediatricians recognize GI problems like Crohn’s disease. The stool calprotectin test along with blood tests serve as excellent screens. I have seen pediatricians using these tests more so I think we are seeing less diagnostic delays than in the past. At the same, IBD can be tricky with symptoms that overlap with common concerns.