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Real-world Crohn’s study shows genetic link to immunogenicity, biosimilar equivalence

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Patients with Crohn’s disease who carried an HLA-DQA1*05 haplotype showed an increased risk for developing immunogenicity to anti-tumor necrosis factor therapy, but immunomodulators appeared to protect against immunogenicity, according to real-world data presented at the 13th Congress of the European Crohn’s and Colitis Organisation.

“We also reported comparative data between Remicade and CT-P13 showing that no differences between originator and biosimilar infliximab in efficacy, safety or immunogenicity,” Nick A. Kennedy, FRACP, of the IBD Pharmacogenetics research group at University of Exeter, told Healio Gastroenterology and Liver Disease.

Kennedy and colleagues presented a variety of data from the Personalized Anti-TNF Therapy in Crohn’s disease (PANTS) study, a 3-year prospective observational study, which Kennedy described as “the largest prospective cohort of Crohn’s patients treated with anti-TNF with over 1,600 patients across 118 U.K. sites.”

The researchers evaluated primary non-response, loss of response and adverse drug reactions among a total of 1,610 patients aged 6 years or older (49% male; median age, 33 years) who were treated with Remicade (infliximab, Janssen; 47%), biosimilar infliximab (CT-P13, Celltrion; 12%), or Humira (adalimumab, AbbVie; 41%).

Primary non-response at weeks 12-14 was 21% among those treated with originator infliximab, 20% among those treated with biosimilar infliximab, and 26% among those treated with adalimumab. However, “there were important baseline differences between the populations treated with these drugs,” Kennedy noted.

Higher BMI was associated with primary non-response for adalimumab (P < .001) and with a lower chance of week 14 remission for both infliximab (P = .006) and adalimumab (P < .001). Low drug concentration was associated with higher primary non-response and lower week 14 remission for both drugs (P < .0001 for both outcomes for adalimumab; P = .002 for primary non-response and P < .001 for remission for infliximab).

Kennedy added that they also observed “significant associations of BMI and drug concentration with outcome at 54 weeks.”

At week 54, 40% of patients treated with originator infliximab, 38% of those treated with biosimilar infliximab, and 34% of those treated with adalimumab were in remission. At the same time point, 28%, 32% and 10% developed immunogenicity, which rose to 40%, 36% and 17% by 2 years. Immunogenicity rates were significantly higher for infliximab vs. adalimumab (P < .0001), but were comparable between originator and biosimilar infliximab (P = .21).

Further, immunogenicity was associated with lack of remission at week 54 (P < .0001 for infliximab, P = 0.01 for adalimumab), and the risk for immunogenicity was reduced by immunomodulator use for both infliximab (HR = 0.37; P < 0.0001) and adalimumab (HR = 0.36, P < .0001).

“The benefits of immunomodulator use on response were seen at week 14 for both drugs, and for infliximab at week 54,” Kennedy said. “The risk of immunogenicity is lower for adalimumab compared to infliximab and for both drugs is lower in patients on immunomodulators. For both drugs immunogenicity is associated with a poorer outcome at week 54.”

The researchers noted that 9% of infliximab-treated patients and 6% of adalimumab-treated patients discontinued therapy due to serious adverse events, which included three deaths from Crohn’s disease and two deaths possibly due to drug-related acute respiratory illness.

Finally, Kennedy and colleagues reported results from their study of genetic susceptibility to immunogenicity in a separate abstract. They assessed genotype data on 1,284 patients who were followed prospectively for at least 1 year after starting anti-TNF therapy.

“Immunogenicity for both drugs is associated with carriage of the HLA-DQA1*05 haplotype, independent of immunomodulator use,” Kennedy said.

“We strongly believe that this type of research is essential to developing cost effective, treatment strategies for patients with inflammatory bowel disease in order to maximize benefit,” PANTS study investigator Tariq Ahmad, MD, head of the Inflammatory Bowel Disease and Pharmacogenetics Research Group at the University of Exeter, and consultant gastroenterologist at the Royal Devon and Exeter Hospital, U.K., said in a press release. “The results from PANTS suggest there are opportunities to optimize the management of anti-TNF therapies and to prevent treatment failure.” – by Adam Leitenberger

Reference:

Kennedy NA, et al. Abstract OP031. Presented at: 13th Congress of ECCO. Feb. 14-17, 2018; Vienna.

Sazonovs A, et al. Abstract OP013. Presented at: 13th Congress of ECCO. Feb. 14-17, 2018; Vienna.

Disclosures: Kennedy reports financial relationships with AbbVie, MSD, Celltrion, NAPP, Pfizer, Celgene, Takeda, Pharmacosmos, Dr Falk, Allergan, Norgine and Janssen, and non-financial support from Immundiagnostik. Please visit the ECCO website for all authors’ relevant financial disclosures.

Editor's note: This article was updated on March 15 with additional information from the study authors.