Clinical trial NCT05813860: HLADQA1*05 Genotype and the Efficacy of Treatment With Infliximab in Chinese Population Crohn's Disease
Official title: Preemptive HLADQA1*05 Genotyping for the Use of Infliximab in Chinese Crohn's Disease：A Multicenter, Prospective, Controlled, Randomized Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Crohn Disease
Infliximab
Lead sponsor: Sixth Affiliated Hospital, Sun Yat-sen University
Sponsor class: OTHER
First posted: 2023-04-14
Enrollment: 976
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Crohn's disease (CD) is a chronic non-specific inflammatory disease of the intestine. Infliximab (IFX) is a kind of one of the anti-tumor necrosis factor agents (anti-TNF) and is the main clinical treatment drug for Crohn's disease, but approximately 30-50% of patients develop a secondary non-response to respond within one year. The main cause of secondary non-response failure is the formation of anti-IFX anti-drug antibodies (ADA). The human leukocyte antigen (HLA) gene is a complex allele that has been associated with susceptibility to a variety of diseases. Studies have shown that HLADQA1\*05 allele carriage significantly increases the immunogenicity of anti-tumor necrosis factor agents (anti-TNF) and the risk of ADA formation, resulting in a significant reduction in the efficacy of IFX. Our previous retrospective study found an increased risk of ADA, IFX failure to respond and discontinuation in patients with HLADQA1\*05 variants, and that IFX in combination with immunosuppression improved clinical outcomes in wild-type genotype patients, whereas combination therapy in patients with variant genotype did not optimize clinical outcomes significantly. Therefore, we believe that the impact of HLADQA1\*05 on the efficacy of IFX in the Chinese population is unclear, and the combination of immunosuppressants in patients with variant HLADQA1\*05 genotype remains to be validated due to insufficient sample size. We hypothesized that HLADQA1\*05 wild-type CD patients would have better clinical remission when treated with IFX than HLADQA1\*05 variant patients and that the combination of immunosuppressants would improve the outcome in wild-type patients but not in variant patients. By advancing this project, we hope to provide high quality evidence on the clinical use of IFX in Crohn's disease in the Chinese population and help physicians to be more selective in the use of IFX alone or in combination with azathioprine, or to switch treatment in a timely manner.


Eligibility criteria: Inclusion Criteria:

* Participants with Crohn's disease who meet the diagnostic criteria of the Consensus Opinion on the Diagnosis and Treatment of Inflammatory Bowel Disease (Beijing, 2018)
* Meet the indications for IFX use
* CDAI score of 220-450; age≥18 years, regardless of gender
* Participants or family members able to understand the study protocol and willing to participate in this study by providing written informed consent

Exclusion Criteria:

* NUDT 15 CT and TT genotypes; previous treatment with IFX and/or other anti-TNF biologics
* Participants who are proposed to have given birth and/or breastfeeding in the 12 months
* those with immunosuppressive intolerance or contraindications
* concurrent chronic diseases or factors of other systems (including severe cardiopulmonary, hepatic and renal, neurological, psychiatric, rheumatic and immune diseases, alcoholism, drug dependence, other chronic active diseases and long-term hormonal or immunosuppressive drugs)
* Excluding infectious diseases (tuberculosis, etc.)
* Excluding tumor-related diseases (lymphoma, gastrointestinal tract tumors, etc.)
* any medical condition/combined surgery/medication/other clinically significant abnormal laboratory tests which, in the judgment of the investigator, may affect the results of the test
* Known refusal or inability to follow protocol requirements for any reason (including planned clinical visits and examinations)

Primary outcomes:
measure: Clinical remission without corticosteroid use at 102 weeks
timeFrame: 102 weeks
Secondary outcomes:
measure: Clinical response at 14 weeks
timeFrame: 14 weeks
measure: Positive for ADA
timeFrame: 102 weeks
measure: IFX Intensive Therapy
timeFrame: 102 weeks
measure: IFX Failure to Respond
timeFrame: 102 weeks
measure: Adverse drug events
timeFrame: 102 weeks
measure: IFX discontinuation
timeFrame: 102 weeks
Other outcomes:
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