From the AGA Journals

Anti-TNFs equal in Crohn’s disease

Dr. Stephen Hanauer
The retrospective cohort study of Medicare data tells the good, the bad, and the ugly about biologic therapy for Crohn's disease circa 2006-2010. The good is that therapy is associated with low hospitalization and surgery rates during the 4-year interval of observation. These findings are consistent with placebo-controlled trials of infliximab and adalimumab in Crohn's disease where Crohn's-related hospitalizations and surgeries were reduced within 1-year maintenance trials. However, the bad and the ugly relate to persistence data with each. Only 28%-31% of patients were still on the respective therapies at 12 months. This speaks to lack of optimization for effectiveness of treatment as the anti-TNF biologics are indicated for both induction and maintenance of Crohn's disease.

If less than a third of all patients initiated on treatment are still receiving maintenance therapies after 1 year, then something is wrong! Up to and during the observation period we were unaware of benefits of combination therapy with biologics and immunosuppressives and the study does not describe the impact of combination treatment on persistence and less than 4% of the cohorts were newly treated with immunosuppressives and about one-third were receiving them in combination. We are learning more about the prevention of immunogenicity and the role of therapeutic drug monitoring. I hope that in the next review between 2010 and 2014 we will be able to see an improvement in persistence along with longer-term reductions in hospitalizations and surgeries.


Dr. Stephen B. Hanauer, professor of medicine, Northwestern University Feinberg School of Medicine, and medical director, Digestive Health Center, Chicago. He has served as a consultant for AbbVie and Janssen and has received institutional research support from both companies.


 

FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY

There is no significant difference between infliximab and adalimumab in Crohn’s disease, reported Dr. Mark T. Osterman and his colleagues in the May 1 issue of Clinical Gastroenterology and Hepatology (doi:10.1016/j.cgh.2013.06.010).

Indeed, in a study that they called "one of the first to directly compare the effectiveness of these two therapies for CD [Crohn’s disease]," the researchers calculated that rates of hospitalization and surgery while on these therapies were statistically similar, providing "justification for allowing patients’ preferences to be a major factor when choosing between these two medications."

Dr. Osterman of the department of medicine at the University of Pennsylvania, Philadelphia, and his colleagues conducted a retrospective cohort analysis of Medicare data on new users of the either adalimumab or infliximab between 2006 and 2010.

Participants had no history of using any anti–tumor necrosis factor (TNF) medications before the index prescription, as well as a diagnosis of Crohn’s in the 12 months prior.

Exclusion criteria included age greater than 85 years on the index anti-TNF prescription date; a coexisting diagnosis of rheumatoid arthritis, psoriasis, psoriatic arthritis, or ankylosing spondylitis; or a diagnosis of ulcerative colitis on or immediately preceding the index date.

In total, the authors analyzed data on 1,445 infliximab patients and 865 adalimumab patients, more than 60% of whom were female and more than 90% of whom were white.

First, the authors assessed the persistence of each drug. They found that after 26 weeks of therapy, 49% of infliximab patients were still taking the drug, as were 47% of adalimumab users (adjusted odds ratio, 0.98; 95% confidence interval 0.81-1.19).

Similarly, by 1 year, the rates of persistence were 31% and 28% for infliximab and adalimumab, respectively (adjusted OR, 1.08; 95% CI, 0.86-1.37).

Next, the authors analyzed surgery-related outcomes. They found that although infliximab patients had a numerically lower incidence of surgery (including bowel resection, ostomy creation, or treatment of a perforation or abscess), the difference did not reach statistical significance (5.5 vs. 6.9 surgeries per 100 person-years, respectively; adjusted hazard ratio, 0.79; 95% CI, 0.60-1.05).

The final outcome assessed was the rate of hospitalizations attributed to Crohn’s disease. Here, too, Dr. Osterman found no significant difference between infliximab (11.8/100 patient-years) and adalimumab patients (15.4/100 patient-years) (adjusted HR, 0.88; 95% CI, 0.72-1.07).

The researchers did concede several limitations, including the fact that they did not compare adverse event rates in their analysis, although they stated that, "In general, the safety profiles of infliximab and adalimumab are believed to be similar with a few exceptions."

Dr. Osterman also wrote that the observational nature of the present analysis is by definition less robust than a head-to-head clinical trial; however, given the extreme cost of such studies, such potentially more definitive analyses "are unlikely to ever be undertaken."

Nevertheless, the current retrospective study should "allow patients, physicians, and insurers to develop rational treatment strategies and guidelines" in the treatment of CD.

Dr. Osterman and several of his coauthors disclosed financial relationships with pharmaceutical companies, including the makers of infliximab and adalimumab, Janssen Biotech and AbbVie, respectively. The researchers disclosed grant funding for this study from the Agency for Healthcare Research and Quality and the National Institutes of Health.

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