VIENNA — People with Crohn’s disease could be one step closer to an individualized approach to tumor necrosis factor inhibitor therapy, thanks to the Personalised Anti-TNF Therapy in Crohn’s Disease (PANTS) study (NCT03088449).
Interim 54-week data from the trial show that older age, a higher body mass index, and low drug levels are associated with primary nonresponse rates for infliximab (Remicade), the biosimilar CT-P13, and adalimumab (Humira).
And for patients who had a primary nonresponse at week 54, “week 14 status was a strong predictor of the week 54 outcomes,” said investigator Nicholas Kennedy, MBBS, from the University of Exeter in the United Kingdom.
Primary nonresponse at week 14 was defined as treatment failure or the need for corticosteroid therapy.
The significant associations between outcome at 14 weeks and body mass index, immunomodulator use, and drug concentration persisted at 54 weeks, Kennedy reported here at the European Crohn’s and Colitis Organisation (ECCO) 2018 Congress, where the PANTS study won the ECCO Congress Best Investigator-Initiated Study Abstract Award.
PANTS Study
The 1601 adults and children who participated in the 3-year prospective study were older than 6 years and were being treated with TNF inhibitors at one of 118 sites in the United Kingdom. All had evidence of Crohn’s disease activity at enrollment, indicated by a C-reactive protein level above 3 mg/L or a calprotectin level of at least 50 µg/g.
In the study cohort, 49% of participants were male, median age was 33 years, and median disease duration was 3 years.
Overall, 47% of the participants were treated with infliximab, 12% with CT-P13, and 41% with adalimumab. At baseline, 44% of patients were being treated with azathioprine, 27% with steroids, 8% with mercaptopurine, and 5% with methotrexate.
Remission was defined as a Harvey-Bradshaw Index score of 3 points or less, a C-reactive protein level no higher than 3 mg/L, and no use of concomitant steroids. Remission rates at week 54 were 40% in the infliximab and CT-P13 groups and 34% in the adalimumab group.
At 12 to 14 weeks, primary nonresponse rates were 21% for infliximab, 21% for CT-P13, and 26% for adalimumab.
Insight Into Immunogenicity
At week 54, the association between immunogenicity — the only data beyond 1 year presented at the congress — and nonremission was significant for the three agents (P < .0001).
Table. Immunogenicity Rates
| TNF Inhibitor | Week 54, % | 3 Years, % |
|---|---|---|
| Infliximab | 26 | 42 |
| CT-P13 | 28 | 38 |
| Adalimumab | 11 | 23 |
“This was an uncontrolled trial with physicians using anti-TNF in a real-world setting for fairly standard indications of luminal Crohn’s disease,” Kennedy said. Because participants differed in a number of important characteristics at baseline, “we have not attempted to make statistical comparisons between infliximab and adalimumab for this reason.”
Immunomodulator use significantly reduced the risk for immunogenicity for infliximab and CT-P13 (hazard ratio [HR], 0.37; P < .0001) and for adalimumab (HR, 0.34; P < .0001).
A Positive Effect for Immunomodulators
“The data suggest that immunogenicity to an anti-TNF may influence long-term effectiveness, a process that may be mediated by concomitant immune modulators,” said Gilaad Kaplan, MD, from the University of Calgary in Canada.
“These data may aid clinicians in choosing between anti-TNF agents, and ultimately may provide information on the positioning of anti-TNF with biologics of other mechanisms,” he told Medscape Medical News.
Patients were taking immunomodulators at baseline at the discretion of their physicians. “In our data, there does not seem to be any difference between patients on azathioprine or methotrexate,” Kennedy reported.
“Monoclonal antibody biologic therapies, such as infliximab and adalimumab, are prone to immunogenicity and loss of response, particularly infliximab,” said Arthur Barrie of the University of Pittsburgh Medical Center in Pennsylvania.
The PANTS study shows that concomitant immunomodulators can protect against loss of response by suppressing immunogenicity,” said Arthur Barrie, MD, PhD, from the University of Pittsburgh Medical Center.
Biologic and Biosimilar Similarities
Another leg of the PANTS trial was designed to assess the initial experience with the CP-P13 biosimilar in the United Kingdom. There were no significant differences in primary nonresponse rates, efficacy, safety, or immunogenicity between the infliximab originator and the biosimilar, Kennedy reported.
Serious adverse events led 140 participants (9%) to withdraw from treatment. In the first 52 weeks of the study, five participants died: three from Crohn’s disease and two from acute respiratory illnesses that might have been related to treatment.
“Five is too small a number to draw any statistically significant conclusions,” Kennedy said. However, “it’s interesting to note that all five patients had primary nonresponse, and four of the five were exposed to concomitant steroids.”
“Personalized medicine is necessary in the era of multimechanistic biologics for the treatment of Crohn’s disease,” said Kaplan. “PANTS brings us closer to practicing personalized medicine for Crohn’s disease.”
AbbVie, MSD, Pfizer, NAPP, Celltrion, and Celgene provide financial support for the PANTS study, and Immundiagnostik provides nonfinancial support. Dr Kennedy reports financial relationships with Takeda, Pharmacosmos, Dr Falk Pharma, Allergan, AbbVie, Janssen, and Norgine. Dr Kaplan reports financial relationships with Janssen and AbbVie. Dr Barrie has disclosed no relevant financial relationships.
European Crohn’s and Colitis Organisation (ECCO) 2018 Congress: Abstract OP031. Presented February 17, 2018.
Follow Medscape Gastro on Twitter @MedscapeGastro and Damian McNamara @MedReporter
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