UK Patients of Bangladeshi Descent with Crohn's Disease Respond Less Well to TNF Antagonists Than Caucasian Patients.

BACKGROUND: Patients with inflammatory bowel disease are currently managed with the assumption that trial data are applicable to all ethnic groups. Previous studies demonstrate differences in disease severity and phenotype of Asian patients with Crohn's disease (CD), including Bangladeshi Asians within the UK. No study has evaluated the impact of ethnicity on response to anti-TNFs. AIM: Our primary endpoint was a comparison of failure-free survival on first prescribed anti-TNF (anti-tumor necrosis factor) therapy in UK Bangladeshi and Caucasian patients with CD. Our secondary aims were to evaluate disease phenotype, indication for anti-TNF prescription, and duration from diagnosis until first anti-TNF prescribed between groups. METHODS: The records of consecutive outpatient appointments over a 12-month period were used to identify Caucasian and Bangladeshi patients prescribed an anti-TNF for CD. Information on patient demographics, ethnicity, disease phenotype, immunomodulator use, outcome from first biologic, duration of therapy, and reason for cessation was recorded. RESULTS: In total, 224 Caucasian and Bangladeshi patients were prescribed an anti-TNF for CD. Bangladeshi patients started an anti-TNF 4.3 years earlier after diagnosis than Caucasian patients (3.9 years vs. 8.2 years: p < 0.01). Bangladeshi patients experienced shorter failure-free survival than Caucasian patients (1.8 vs. 4.8 years p < 0.01). By 2 years, significantly more Bangladeshi patients had stopped anti-TNF due to loss of response (OR 6.35, p < 0.01). CONCLUSIONS: This is the first study to suggest that Bangladeshi patients resident in the UK with CD respond less well to treatment with TNF antagonists than Caucasian patients.

Differential immunogenicity of homologous versus heterologous boost in Ad26.COV2.S vaccine recipients.

BACKGROUND: Protection offered by coronavirus disease 2019 (COVID-19) vaccines wanes over time, requiring an evaluation of different boosting strategies to revert such a trend and enhance the quantity and quality of Spike-specific humoral and cellular immune responses. These immunological parameters in homologous or heterologous vaccination boosts have thus far been studied for mRNA and ChAdOx1 nCoV-19 vaccines, but knowledge on individuals who received a single dose of Ad26.COV2.S is lacking. METHODS: We studied Spike-specific humoral and cellular immunity in Ad26.COV2.S-vaccinated individuals (n = 55) who were either primed with Ad26.COV2.S only (n = 13) or were boosted with a homologous (Ad26.COV2.S, n = 28) or heterologous (BNT162b2, n = 14) second dose. We compared our findings with the results found in individuals vaccinated with a single (n = 16) or double (n = 44) dose of BNT162b2. FINDINGS: We observed that a strategy of heterologous vaccination enhanced the quantity and breadth of both Spike-specific humoral and cellular immunity in Ad26.COV2.S-vaccinated individuals. In contrast, the impact of the homologous boost was quantitatively minimal in Ad26.COV2.S-vaccinated individuals, and Spike-specific antibodies and T cells were narrowly focused to the S1 region. CONCLUSIONS: Despite the small sample size of the study and the lack of well-defined correlates of protection against COVID-19, the immunological features detected support the utilization of a heterologous vaccine boost in individuals who received Ad26.COV2.S vaccination. FUNDING: This study is partially supported by the Singapore Ministry of Health's National Medical Research Council under its COVID-19 Research Fund (COVID19RF3-0060, COVID19RF-001, and COVID19RF-008), The Medical College St. Bartholomew's Hospital Trustees - Pump Priming Fund for SMD COVID-19 Research.