Tariq Ahmad

Tariq Ahmad
Royal Devon and Exeter NHS Foundation Trust · Department of Gastroenterology

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342
Publications
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Publications

Publications (342)
Article
Full-text available
Background During illness, adaptations of the hypothalamic–pituitary‐thyroid axis reduce energy expenditure, protein catabolism and modulate immune responses to promote survival. Lower serum free triiodothyronine‐to‐thyroxine (fT3/fT4) ratio has been linked to non‐response to treatment in a range of diseases, including in biologic‐treated patients...
Article
Full-text available
Background COVID-19 vaccine-induced antibody responses are reduced in patients with inflammatory bowel disease (IBD) taking anti-TNF or tofacitinib after two vaccine doses. We sought to assess whether immunosuppressive treatments were associated with reduced antibody and T-cell responses in patients with IBD after a third vaccine dose. Methods VIP...
Article
Full-text available
Genome-wide association studies (GWASs) have identified hundreds of loci associated with Crohn’s disease (CD). However, as with all complex diseases, robust identification of the genes dysregulated by noncoding variants typically driving GWAS discoveries has been challenging. Here, to complement GWASs and better define actionable biological targets...
Article
Full-text available
Background Anti‐drug antibodies are associated with treatment failure to anti‐TNF agents in patients with inflammatory bowel disease (IBD). Aim To assess whether immunogenicity to a patient's first anti‐TNF agent would be associated with immunogenicity to their second, irrespective of drug sequence Methods We conducted a UK‐wide, multicentre, ret...
Article
Objective Antitumour necrosis factor (TNF) drugs impair serological responses following SARS-CoV-2 vaccination. We sought to assess if a third dose of a messenger RNA (mRNA)-based vaccine substantially boosted anti-SARS-CoV-2 antibody responses and protective immunity in infliximab-treated patients with IBD. Design Third dose vaccine induced anti-...
Preprint
Patients with inflammatory bowel disease (IBD) treated with anti-TNF therapy exhibit attenuated humoral immune responses to vaccination against SARS-CoV-2. The gut microbiota and its functional metabolic output, which are perturbed in IBD, play an important role in shaping host immune responses. We explored whether the gut microbiota and metabolome...
Article
Anti tumour necrosis factor (anti-TNF) drugs increase the risk of serious respiratory infection and impair protective immunity following pneumococcal and influenza vaccination. Here we report SARS-CoV-2 vaccine-induced immune responses and breakthrough infections in patients with inflammatory bowel disease, who are treated either with the anti-TNF...
Conference Paper
Background Antibody responses following SARS-CoV-2 infection or a single-dose of SARS-CoV-2 vaccine are impaired in patients with inflammatory bowel disease treated with anti-TNF compared to those treated with vedolizumab, a gut-selective anti-integrin α4β7 monoclonal antibody. Here we sought to determine if patients treated with infliximab have at...
Article
Background Robust COVID-19 vaccine-induced antibody (Ab) responses are important for protective anti-viral immunity. Data are urgently needed to determine whether vaccine-induced immunity is impacted by commonly used immunosuppressive drug regimens in IBD. Methods We prospectively recruited 447 adults (90 healthy controls and 357 IBD) at nine UK c...
Article
Background Anti-TNF treatment failure is common. Primary non-response and loss of response are frequently caused by low anti-TNF drug levels mediated, principally, by the formation of anti-drug antibodies which can be mitigated by concomitant immunomodulator use. Previous small studies in patients with IBD suggest that antibodies formed prior to tr...
Preprint
Full-text available
We report SARS-CoV-2 vaccine-induced immunity and risk of breakthrough infections in patients with inflammatory bowel disease treated with infliximab, a commonly used anti-TNF drug and those treated with vedolizumab, a gut-specific antibody targeting integrin a4b7 that does not impact systemic immunity. In infliximab-treated patients, the magnitude...
Conference Paper
Introduction Anti-TNF treatment failure in patients with IBD is common. International guidelines recommend switching out of class when anti-TNF drug levels are therapeutic and within class with an immunomodulator when anti-TNF drug levels are suboptimal and associated with antibody development.We sought to define the: 1) risk of immunogenicity to a...
Conference Paper
Introduction Pressure on critical care services because of further COVID-19 surges have forced governments to prioritise primary vaccination to vulnerable groups. To extend limited vaccine supplies, many countries including the United Kingdom have also delayed second vaccine doses, trading maximal effectiveness for a lower level of protective immun...
Article
Background Etrolizumab is a gut-targeted anti-β7 integrin monoclonal antibody. In a previous phase 2 induction study, etrolizumab significantly improved clinical remission versus placebo in patients with moderately to severely active ulcerative colitis. We aimed to compare the safety and efficacy of etrolizumab with infliximab in patients with mode...
Article
Background Etrolizumab is a gut-targeted, anti-β7 integrin, monoclonal antibody. In an earlier phase 2 induction study, etrolizumab significantly improved clinical remission compared with placebo in patients with moderately to severely active ulcerative colitis. We aimed to evaluate the efficacy and safety of etrolizumab in patients with moderately...
Article
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Background and aims: Infliximab attenuates serological responses to SARS-CoV-2 infection. Whether this is a class effect, or if anti-TNF level influences serological responses, remains unknown. Methods: Seroprevalence and the magnitude of SARS-CoV-2 nucleocapsid antibody responses were measured in surplus serum from 11422 (53.3% (6084) male; med...
Preprint
Full-text available
To inform healthcare policy for immunosuppressed patients there is a need to define SARS-CoV-2 vaccine responses. Here we report SARS-CoV-2 vaccine-induced antibody and T cell responses in patients treated with anti-tumour necrosis factor (anti-TNF), a commonly used biologic in inflammatory diseases, compared to patients treated with vedolizumab, a...
Article
Background & aims: Because of COVID-19 public health restrictions, telemedicine has replaced conventional outpatient follow up for most patients with chronic immune-mediated inflammatory disorders treated with biologic drugs. Innovative solutions to facilitate remote therapeutic drug monitoring are therefore required. Low-volume intracapillary blo...
Article
Background Identification of biomarkers that predict severe Crohn’s disease is an urgent unmet research need, but existing research is piecemeal and haphazard. Objective To identify biomarkers that are potentially able to predict the development of subsequent severe Crohn’s disease. Design This was a prognostic systematic review with meta-analysi...
Preprint
Full-text available
Genome-wide association studies (GWAS) have identified hundreds of loci associated with Crohns disease (CD); however, as with all complex diseases, deriving pathogenic mechanisms from these non-coding GWAS discoveries has been challenging. To complement GWAS and better define actionable biological targets, we analysed sequence data from more than 3...
Conference Paper
Background Anti-TNF drugs increase the risk of serious respiratory infections and impair protective immunity following pneumococcal, influenza, and viral hepatitis vaccinations. Therefore, we sought to determine whether patients with inflammatory bowel disease treated with infliximab have attenuated serological responses following SARS-CoV-2 infect...
Conference Paper
Background Timely diagnosis of inflammatory bowel disease (IBD) is important because earlier use of biologic therapies leads to mucosal healing, a reduction in hospitalisations and surgeries and improvements in quality of life. In the United Kingdom, general practitioners refer patients with symptoms suggestive of IBD to colorectal surgeons, emerge...
Conference Paper
Background Anti-TNF (aTNF) treatment failure in patients with IBD is common. International guidelines recommend switching out of class when aTNF drug levels are therapeutic and within class with an immunomodulator when aTNF drug levels are suboptimal and associated with antibody development. We sought to define the: 1) risk of immunogenicity to a s...
Conference Paper
Background Given the existential threat from COVID-19 and the consequent restrictive public health measures it is perhaps unsurprising that SARS-CoV-2 infection has been linked to increases in rates of depression in the general population. Few studies, however have addressed anxiety and depression in patients with inflammatory bowel disease (IBD) d...
Conference Paper
Full-text available
Background Because of COVID-19 public health restrictions, telemedicine has replaced conventional outpatient follow up for most patients with chronic immune-mediated inflammatory disorders treated with biologic drugs. Innovative solutions to facilitate remote therapeutic drug monitoring are therefore required. Low-volume intracapillary blood sampli...
Article
Full-text available
Objective: Delayed second dose SARS-CoV-2 vaccination trades maximal effectiveness for a lower level of immunity across more of the population. We investigated whether patients with inflammatory bowel disease treated with infliximab have attenuated serological responses to a single dose of a SARS-CoV-2 vaccine. Design: Antibody responses and ser...
Preprint
Full-text available
Background Delayed second-dose SARS-CoV-2 vaccination trades maximal effectiveness for a lower level of immunity across more of the population. We investigated whether patients with inflammatory bowel disease treated with infliximab have attenuated serological responses to a single-dose of a SARS-CoV-2 vaccine. Methods Antibody responses and seroco...
Article
Full-text available
Objective Antitumour necrosis factor (anti-TNF) drugs impair protective immunity following pneumococcal, influenza and viral hepatitis vaccination and increase the risk of serious respiratory infections. We sought to determine whether infliximab-treated patients with IBD have attenuated serological responses to SARS-CoV-2 infections. Design Antibo...
Article
In this Article, author Marquis P. Vawter was missing from the Genome Aggregation Database Consortium list. They are associated with the affiliation: ‘Department of Psychiatry & Human Behavior, University of California Irvine, Irvine, CA, USA’, and contributed to the generation of the primary data incorporated into the gnomAD resource. The original...
Article
Full-text available
A Correction to this paper has been published: https://doi.org/10.1038/s41591-020-01185-6.
Article
SARS-CoV-2 has caused a global health crisis and mass vaccination programmes provide the best opportunity for controlling transmission and protecting populations. Despite the impressive clinical trial results of the BNT162b2 (Pfizer/BioNTech), ChAdOx1 nCoV-19 (Oxford/AstraZeneca), and mRNA-1273 (Moderna) vaccines, important unanswered questions rem...
Conference Paper
Full-text available
Introduction Tofacitinib is an oral partially selective Janus kinase inhibitor approved for the treatment of refractory moderate to severe ulcerative colitis (UC). Real-world experience of patients with UC treated with tofacitinib is however limited, and safety concerns over the risk of venous thromboembolism (VTE) have recently emerged. Further, f...
Conference Paper
Introduction Anti-drug antibodies can affect biopharmaceutical pharmacokinetics by increasing or decreasing drug clearance. Drug-tolerant (total), unlike drug-sensitive (free), antibody assays permit antibodies to be measured in the presence of drug.We aimed to confirm the positivity threshold of our total anti-tumour necrosis factor (TNF) antibody...
Article
Full-text available
Background: Colonoscopic surveillance in patients with inflammatory bowel disease (IBD) leads to earlier detection of colorectal cancer (CRC) and reduces CRC-associated mortality. However, it is limited by poor adherence in practice. Aim: To identify missed opportunities to detect IBD-associated CRC at our hospital METHODS: We undertook root-cau...
Article
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Background: When used proactively, drug-tolerant anti-tumour necrosis factor (TNF) antibody assays provide early opportunity to suppress immunogenicity. Aim: To validate positivity thresholds of IDKmonitor drug-tolerant anti-infliximab and -adalimumab antibody assays. Methods: We applied positivity thresholds, defined by testing sera from 498...
Article
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LINKED CONTENT This article is linked to Gordon et al and Mahmoud & Itzkowitz papers. To view these articles, visit https://doi.org/10.1111/apt.16155 and https://doi.org/10.1111/apt.16175
Article
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LINKED CONTENT This article is linked to Bangma et al paper. To view this article, visit https://doi.org/10.1111/apt.15762
Article
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Background Delay in the diagnosis of inflammatory bowel disease (IBD) is common and contemporary UK studies are lacking. Aim To determine factors associated with, and the consequences of, a prolonged time to diagnosis in IBD. Methods This quality improvement study included 304 adults with a new IBD diagnosis made between January 2014 and December...
Article
Full-text available
Background: Gastro-oesophageal reflux disease (GORD) is associated with multiple risk factors but determining causality is difficult. We used a genetic approach [Mendelian randomization (MR)] to identify potential causal modifiable risk factors for GORD. Methods: We used data from 451 097 European participants in the UK Biobank and defined GORD...
Article
Background and aims We sought to define temporal changes in prevalence of inflammatory bowel disease (IBD) in East Devon, UK, in order to facilitate service planning over the next 5 years. Methods Multiple primary and secondary care databases were used to identify and verify cases. Point prevalence and incidence of IBD were reported in April 2017...
Article
Background: Anti-TNF exposure has been linked to demyelination events. We sought to describe the clinical features of demyelination events following anti-TNF treatment and test whether affected patients were genetically predisposed to multiple sclerosis (MS). Methods: We conducted a case-control study to describe the clinical features of demyeli...
Article
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Human genetic variants predicted to cause loss-of-function of protein-coding genes (pLoF variants) provide natural in vivo models of human gene inactivation and can be valuable indicators of gene function and the potential toxicity of therapeutic inhibitors targeting these genes1,2. Gain-of-kinase-function variants in LRRK2 are known to significant...
Article
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Genetic variants that inactivate protein-coding genes are a powerful source of information about the phenotypic consequences of gene disruption: genes that are crucial for the function of an organism will be depleted of such variants in natural populations, whereas non-essential genes will tolerate their accumulation. However, predicted loss-of-fun...
Article
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Structural variants (SVs) rearrange large segments of DNA1 and can have profound consequences in evolution and human disease2,3. As national biobanks, disease-association studies, and clinical genetic testing have grown increasingly reliant on genome sequencing, population references such as the Genome Aggregation Database (gnomAD)4 have become int...
Article
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Naturally occurring human genetic variants that are predicted to inactivate protein-coding genes provide an in vivo model of human gene inactivation that complements knockout studies in cells and model organisms. Here we report three key findings regarding the assessment of candidate drug targets using human loss-of-function variants. First, even e...
Article
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The acceleration of DNA sequencing in samples from patients and population studies has resulted in extensive catalogues of human genetic variation, but the interpretation of rare genetic variants remains problematic. A notable example of this challenge is the existence of disruptive variants in dosage-sensitive disease genes, even in apparently hea...
Article
Objective To determine the diagnostic accuracy of calprotectin to diagnose inflammatory bowel disease (IBD) in children in whom general practitioners (GPs) suspected IBD. Design Prospective observational cohort study of a new calprotectin-based primary care referral pathway. Setting 48 GP practices and gastroenterology secondary care services at...
Article
Full-text available
Background: Tofacitinib is a partially selective Janus kinase inhibitor approved for the treatment of refractory moderate to severe ulcerative colitis (UC). We sought to define the effectiveness and adverse effects of tofacitinib in a real-world cohort. Methods: We conducted a retrospective observational cohort study of 134 patients with UC (64%...
Conference Paper
Background Anti-drug antibodies can affect biopharmaceutical pharmacokinetics by increasing or decreasing drug clearance. Drug-tolerant (total), unlike drug-sensitive (free), antibody assays permit antibodies to be measured in the presence of a drug. We sought to confirm the positivity threshold of our total anti-tumour necrosis factor (TNF) antibo...
Article
Full-text available
Background Tofacitinib is a partially selective Janus kinase inhibitor that was approved for the treatment of refractory moderate to severe ulcerative colitis (UC) in 2018. We report the real-world clinical effectiveness and adverse effects of tofacitinib in UC. Methods We conducted a retrospective observational cohort study of tofacitinib-treated...
Conference Paper
Background Proteomic biomarkers have been linked to anti-TNF treatment failure, but previous studies have been insufficiently powered to stratify associations by drug level. The Personalised Anti-TNF Therapy in Crohn’s disease (PANTS) is a prospective UK-wide study investigating treatment failure in 1610 anti-TNF naïve patients. We aimed to identif...
Conference Paper
Full-text available
Background Colonoscopic surveillance in IBD patients can reduce the development of colorectal cancer (CRC) and the rate of CRC-associated death. We recently reported that 27% of IBD patients living in East Devon are managed exclusively in primary care of whom about 23% maybe eligible for colonoscopic surveillance. We devised an outreach programme,...
Conference Paper
Background Colonoscopic surveillance in inflammatory bowel disease (IBD) patients leads to earlier detection of colorectal cancer (CRC) and reduces CRC-associated deaths. However, adherence to international surveillance guidelines in practice is poor. Consequently, we hypothesised that patients with IBD-associated CRC had suboptimal endoscopic surv...
Article
Full-text available
Background Biologic treatments can reactivate viral hepatitis and HIV. Prior to starting biologic therapy, the ECCO guidelines recommend patients are screened for chronic viral infection. We recently diagnosed a patient treated with adalimumab with HIV. As a consequence we sought to assess the effectiveness of our screening process for viral infect...