Publications by category
Journal articles
Hanić M, Vučković F, Deriš H, Bewshea C, Lin S, Goodhand JR, Ahmad T, Trbojević-Akmačić I, Kennedy NA, Lauc G, et al (2023). Anti-TNF Biologicals Enhance the Anti-Inflammatory Properties of IgG N-Glycome in Crohn’s Disease.
Biomolecules,
13(6), 954-954.
Abstract:
Anti-TNF Biologicals Enhance the Anti-Inflammatory Properties of IgG N-Glycome in Crohn’s Disease
Crohn’s disease (CD) is a chronic inflammation of the digestive tract that significantly impairs patients’ quality of life and well-being. Anti-TNF biologicals revolutionised the treatment of CD, yet many patients do not adequately respond to such therapy. Previous studies have demonstrated a pro-inflammatory pattern in the composition of CD patients’ immunoglobulin G (IgG) N-glycome compared to healthy individuals. Here, we utilised the high-throughput UHPLC method for N-glycan analysis to explore the longitudinal effect of the anti-TNF drugs infliximab and adalimumab on N-glycome composition of total serum IgG in 198 patients, as well as the predictive potential of IgG N-glycans at baseline to detect primary non-responders to anti-TNF therapy in 1315 patients. We discovered a significant decrease in IgG agalactosylation and an increase in monogalactosylation, digalactosylation and sialylation during the 14 weeks of anti-TNF treatment, regardless of therapy response, all of which suggested a diminished inflammatory environment in CD patients treated with anti-TNF therapy. Furthermore, we observed that IgG N-glycome might contain certain information regarding the anti-TNF therapy outcome before initiating the treatment. However, it is impossible to predict future primary non-responders to anti-TNF therapy based solely on IgG N-glycome composition at baseline.
Abstract.
Lin S, Hannon E, Waring JF, Reppell M, Smaoui N, Pivorunas VL, Guay H, Chanchlani N, Bewshea C, Bai BYH, et al (2023). DOP88 Understanding the molecular mechanisms of anti-TNF treatment failure: Whole blood DNA methylation changes associated with primary non-response to anti-TNF treatment in patients with Crohn’s disease. Journal of Crohn's and Colitis, 17(Supplement_1), i164-i166.
Liu Z, Le K, Zhou X, Alexander JL, Lin S, Bewshea C, Chanchlani N, Nice R, McDonald TJ, Lamb CA, et al (2023). Neutralising antibody potency against SARS-CoV-2 wild-type and omicron BA.1 and BA.4/5 variants in patients with inflammatory bowel disease treated with infliximab and vedolizumab after three doses of COVID-19 vaccine (CLARITY IBD): an analysis of a prospective multicentre cohort study.
Lancet Gastroenterol Hepatol,
8(2), 145-156.
Abstract:
Neutralising antibody potency against SARS-CoV-2 wild-type and omicron BA.1 and BA.4/5 variants in patients with inflammatory bowel disease treated with infliximab and vedolizumab after three doses of COVID-19 vaccine (CLARITY IBD): an analysis of a prospective multicentre cohort study.
BACKGROUND: Anti-TNF drugs, such as infliximab, are associated with attenuated antibody responses after SARS-CoV-2 vaccination. We aimed to determine how the anti-TNF drug infliximab and the anti-integrin drug vedolizumab affect vaccine-induced neutralising antibodies against highly transmissible omicron (B.1.1.529) BA.1, and BA.4 and BA.5 (hereafter BA.4/5) SARS-CoV-2 variants, which possess the ability to evade host immunity and, together with emerging sublineages, are now the dominating variants causing current waves of infection. METHODS: CLARITY IBD is a prospective, multicentre, observational cohort study investigating the effect of infliximab and vedolizumab on SARS-CoV-2 infection and vaccination in patients with inflammatory bowel disease (IBD). Patients aged 5 years and older with a diagnosis of IBD and being treated with infliximab or vedolizumab for 6 weeks or longer were recruited from infusion units at 92 hospitals in the UK. In this analysis, we included participants who had received uninterrupted biological therapy since recruitment and without a previous SARS-CoV-2 infection. The primary outcome was neutralising antibody responses against SARS-CoV-2 wild-type and omicron subvariants BA.1 and BA.4/5 after three doses of SARS-CoV-2 vaccine. We constructed Cox proportional hazards models to investigate the risk of breakthrough infection in relation to neutralising antibody titres. The study is registered with the ISRCTN registry, ISRCTN45176516, and is closed to accrual. FINDINGS: Between Sept 22 and Dec 23, 2020, 7224 patients with IBD were recruited to the CLARITY IBD study, of whom 1288 had no previous SARS-CoV-2 infection after three doses of SARS-CoV-2 vaccine and were established on either infliximab (n=871) or vedolizumab (n=417) and included in this study (median age was 46·1 years [IQR 33·6-58·2], 610 [47·4%] were female, 671 [52·1%] were male, 1209 [93·9%] were White, and 46 [3·6%] were Asian). After three doses of SARS-CoV-2 vaccine, 50% neutralising titres (NT50s) were significantly lower in patients treated with infliximab than in those treated with vedolizumab, against wild-type (geometric mean 2062 [95% CI 1720-2473] vs 3440 [2939-4026]; p
Abstract.
Author URL.
Liu Z, Le K, Zhou X, Alexander J, Lin S, Bewshea C, Chanchlani N, Nice R, McDonald T, Lamb C, et al (2023). OP24 Neutralising antibody potency against SARS-CoV-2 wild-type and Omicron BA.1 and BA.4/5 variants in infliximab and vedolizumab treated patients with Inflammatory Bowel Disease after three doses of COVID-19 vaccine: a prospective multicentre cohort study. Journal of Crohn's and Colitis, 17(Supplement_1), i32-i34.
Carbery I, Lin S, Chanchlani N, Janjua M, Nice R, McDonald TJ, Bewshea C, Kennedy NA, Ahmad T, Goodhand JR, et al (2023). P649 Does serum triiodothyronine-to-thyroxine (T3/T4) ratio predict therapeutic outcome to anti-TNF therapies in biologic-naïve patients with active luminal Crohn’s disease?. Journal of Crohn's and Colitis, 17(Supplement_1), i778-i778.
Lin S, Chanchlani N, Smith R, Roberts C, Nice R, McDonald TJ, Hamilton B, Bewshea C, Kennedy NA, Goodhand JR, et al (2023). P662 Pre-treatment vitamin D concentrations do not predict therapeutic outcome to anti-TNF therapies in biologic-naïve patients with active luminal Crohn’s disease. Journal of Crohn's and Colitis, 17(Supplement_1), i791-i793.
Chanchlani N, Lin S, Hamilton B, Bewshea C, Thomas A, Smith R, Roberts C, Nice R, McDonald TJ, Goodhand JR, et al (2023). P798 Understanding anti-TNF treatment failure: mechanisms and management of loss of response to anti-TNF therapy, three-year data from the PANTS study. Journal of Crohn's and Colitis, 17(Supplement_1), i928-i930.
Chanchlani N, Lin S, Chee D, Hamilton B, Nice R, Arkir Z, Bewshea C, Cipriano B, Derikx LAAP, Dunlop A, et al (2022). Adalimumab and Infliximab Impair SARS-CoV-2 Antibody Responses: Results from a Therapeutic Drug Monitoring Study in 11 422 Biologic-Treated Patients.
J Crohns Colitis,
16(3), 389-397.
Abstract:
Adalimumab and Infliximab Impair SARS-CoV-2 Antibody Responses: Results from a Therapeutic Drug Monitoring Study in 11 422 Biologic-Treated Patients.
BACKGROUND AND AIMS: Infliximab attenuates serological responses to SARS-CoV-2 infection. Whether this is a class effect, or if anti-tumour necrosis factor [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 11 422 (53.3% [6084] male; median age 36.8 years) patients with immune-mediated inflammatory diseases, stored at six therapeutic drug monitoring laboratories between January 29 and September 30, 2020. Data were linked to nationally held SARS-CoV-2 PCR results to July 11, 2021. RESULTS: Rates of PCR-confirmed SARS-CoV-2 infection were similar across treatment groups. Seroprevalence rates were lower in infliximab- and adalimumab- than vedolizumab-treated patients (infliximab: 3.0% [178/5893], adalimumab: 3.0% [152/5074], vedolizumab: 6.7% [25/375], p
=
0.003). The magnitude of SARS-CoV-2 reactivity was similar in infliximab- vs adalimumab-treated patients (median 4.30 cut-off index [COI] [1.94-9.96] vs 5.02 [2.18-18.70], p
=
0.164), but higher in vedolizumab-treated patients (median 21.60 COI [4.39-68.10, p
Abstract.
Author URL.
Lin S, Kennedy NA, Saifuddin A, Sandoval DM, Reynolds CJ, Seoane RC, Kottoor SH, Pieper FP, Lin K-M, Butler DK, et al (2022). Antibody decay, T cell immunity and breakthrough infections following two SARS-CoV-2 vaccine doses in inflammatory bowel disease patients treated with infliximab and vedolizumab.
Nat Commun,
13(1).
Abstract:
Antibody decay, T cell immunity and breakthrough infections following two SARS-CoV-2 vaccine doses in inflammatory bowel disease patients treated with infliximab and vedolizumab.
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 antibody, infliximab, or with vedolizumab targeting a gut-specific anti-integrin that does not impair systemic immunity. Geometric mean [SD] anti-S RBD antibody concentrations are lower and half-lives shorter in patients treated with infliximab than vedolizumab, following two doses of BNT162b2 (566.7 U/mL [6.2] vs 4555.3 U/mL [5.4], p
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Chee D, Nice R, Hamilton B, Jones E, Hawkins S, Redstone C, Cairnes V, Pohl K, Chanchlani N, Lin S, et al (2022). Patient-led Remote IntraCapillary pharmacoKinetic Sampling (fingerPRICKS) for Therapeutic Drug Monitoring in patients with Inflammatory Bowel Disease.
J Crohns Colitis,
16(2), 190-198.
Abstract:
Patient-led Remote IntraCapillary pharmacoKinetic Sampling (fingerPRICKS) for Therapeutic Drug Monitoring in patients with Inflammatory Bowel Disease.
BACKGROUND AND 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 blood sampling can be undertaken by patients at home and samples returned by post to central laboratories. We sought to report the effect of the COVID-19 pandemic on requests for therapeutic drug monitoring and the equivalence, acceptability and effectiveness of low volume Patient-led Remote IntraCapillary pharmacoKinetic Sampling [fingerPRICKS] compared to conventional venepuncture. METHODS: We undertook a cross-sectional blood sampling methods comparison study and compared sample types using linear regression models. Drug and antidrug antibody levels were measured using standard ELISAs. Acceptability was assessed using a purpose-designed questionnaire. RESULTS: Therapeutic drug monitoring requests for adalimumab (96.5 [70.5-106] per week to 52 [33.5-57.0], p < 0.001) but not infliximab (184.5 [161.2-214.2] to 161 [135-197.5], p = 0.34) reduced during the first UK stay-at-home lockdown compared with the preceding 6 months. Fingerprick sampling was equivalent to conventional venepuncture for adalimumab, infliximab, vedolizumab and ustekinumab drug, and anti-adalimumab and anti-infliximab antibody levels. The median [interquartile range] volume of serum obtained using intracapillary sampling was 195 µL [130-210]. More than 87% [90/103] of patients agreed that intracapillary testing was easy and 69% [71/103] preferred it to conventional venepuncture. In routine care, 75.3% [58/77] of patients returned two blood samples within 14 days to permit remote assessment of biologic therapeutic drug monitoring. CONCLUSIONS: Therapeutic drug monitoring can be undertaken using patient-led remote intracapillary blood sampling and has the potential to be a key adjunct to telemedicine in patients with immune-mediated inflammatory diseases.
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Author URL.
Kennedy NA, Goodhand JR, Bewshea C, Nice R, Chee D, Lin S, Chanchlani N, Butterworth J, Cooney R, Croft NM, et al (2021). Anti-SARS-CoV-2 antibody responses are attenuated in patients with IBD treated with infliximab.
Gut,
70(5), 865-875.
Abstract:
Anti-SARS-CoV-2 antibody responses are attenuated in patients with IBD treated with infliximab
ObjectiveAntitumour 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.DesignAntibody responses in participants treated with infliximab were compared with a reference cohort treated with vedolizumab, a gut-selective anti-integrin α4β7 monoclonal antibody that is not associated with impaired vaccine responses or increased susceptibility to systemic infections. 6935 patients were recruited from 92 UK hospitals between 22 September and 23 December 2020.ResultsRates of symptomatic and proven SARS-CoV-2 infection were similar between groups. Seroprevalence was lower in infliximab-treated than vedolizumab-treated patients (3.4% (161/4685) vs 6.0% (134/2250), p<0.0001). Multivariable logistic regression analyses confirmed that infliximab (vs vedolizumab; OR 0.66 (95% CI 0.51 to 0.87), p=0.0027) and immunomodulator use (OR 0.70 (95% CI 0.53 to 0.92), p=0.012) were independently associated with lower seropositivity. In patients with confirmed SARS-CoV-2 infection, seroconversion was observed in fewer infliximab-treated than vedolizumab-treated patients (48% (39/81) vs 83% (30/36), p=0.00044) and the magnitude of anti-SARS-CoV-2 reactivity was lower (median 0.8 cut-off index (0.2–5.6) vs 37.0 (15.2–76.1), p<0.0001).ConclusionsInfliximab is associated with attenuated serological responses to SARS-CoV-2 that were further blunted by immunomodulators used as concomitant therapy. Impaired serological responses to SARS-CoV-2 infection might have important implications for global public health policy and individual anti-TNF-treated patients. Serological testing and virus surveillance should be considered to detect suboptimal vaccine responses, persistent infection and viral evolution to inform public health policy.Trial registration numberISRCTN45176516.
Abstract.
Chanchlani N, Lin S, Thomas A, Hamilton B, Nice R, Chee D, Kennedy N, Goodhand J, Ahmad T (2021). HMO-4 Immunogenicity to second anti-TNF therapy (IMSAT): implications for sequencing of biologic therapy. Gut, 70(Suppl 4), a31-a32.
Kennedy NA, Lin S, Goodhand JR, Chanchlani N, Hamilton B, Bewshea C, Nice R, Chee D, Cummings JF, Fraser A, et al (2021). Infliximab is associated with attenuated immunogenicity to BNT162b2 and ChAdOx1 nCoV-19 SARS-CoV-2 vaccines in patients with IBD.
Gut,
70(10), 1884-1893.
Abstract:
Infliximab is associated with attenuated immunogenicity to BNT162b2 and ChAdOx1 nCoV-19 SARS-CoV-2 vaccines in patients with IBD.
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 seroconversion rates in infliximab-treated patients (n=865) were compared with a cohort treated with vedolizumab (n=428), a gut-selective anti-integrin α4β7 monoclonal antibody. Our primary outcome was anti-SARS-CoV-2 spike (S) antibody concentrations, measured using the Elecsys anti-SARS-CoV-2 spike (S) antibody assay 3-10 weeks after vaccination, in patients without evidence of prior infection. Secondary outcomes were seroconversion rates (defined by a cut-off of 15 U/mL), and antibody responses following past infection or a second dose of the BNT162b2 vaccine. RESULTS: Geometric mean (SD) anti-SARS-CoV-2 antibody concentrations were lower in patients treated with infliximab than vedolizumab, following BNT162b2 (6.0 U/mL (5.9) vs 28.8 U/mL (5.4) p
Abstract.
Author URL.
Kennedy N, Lin S, Goodhand J, Powell N, Ahmad T, group CIS (2021). OFR-8 Infliximab is associated with attenuated immunogenicity to BNT162b2 and ChAdOx1 nCoV-19 SARS-CoV-2 vaccines. Gut, 70(Suppl 4), a3-a4.
Lin S, Green HD, Hendy P, Heerasing NM, Chanchlani N, Hamilton B, Walker GJ, Heap GA, Hobart J, Martin RJ, et al (2020). Clinical Features and Genetic Risk of Demyelination Following Anti-TNF Treatment.
J Crohns Colitis,
14(12), 1653-1661.
Abstract:
Clinical Features and Genetic Risk of Demyelination Following Anti-TNF Treatment.
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 to test whether affected patients were genetically predisposed to multiple sclerosis [MS]. METHODS: We conducted a case-control study to describe the clinical features of demyelination events following anti-TNF exposure. We compared genetic risk scores [GRS], calculated using carriage of 43 susceptibility loci for MS, in 48 cases with 1219 patients exposed to anti-TNF who did not develop demyelination. RESULTS: Overall, 39 [74%] cases were female. The median age [range] of patients at time of demyelination was 41.5 years [20.7-63.2]. The median duration of anti-TNF treatment was 21.3 months [0.5-99.4] and 19 [36%] patients were receiving concomitant immunomodulators. Most patients had central demyelination affecting the brain, spinal cord, or both. Complete recovery was reported in 12 [23%] patients after a median time of 6.8 months [0.1-28.7]. After 33.0 months of follow-up, partial recovery was observed in 29 [55%] patients, relapsing and remitting episodes in nine [17%], progressive symptoms in three [6%]: two [4%] patients were diagnosed with MS. There was no significant difference between MS GRS scores in cases (mean -3.5 × 10-4, standard deviation [SD] 0.0039) and controls [mean -1.1 × 10-3, SD 0.0042] [p = 0.23]. CONCLUSIONS: Patients who experienced demyelination events following anti-TNF exposure were more likely female, less frequently treated with an immunomodulator, and had a similar genetic risk to anti-TNF exposed controls who did not experience demyelination events. Large prospective studies with pre-treatment neuroimaging are required to identify genetic susceptibility loci.
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Author URL.
Lin S, Chanchlani N, Invergo BM, Anderson MW, Guay HM, Reppell M, Butler JW, Goodhand JR, Ahmad T, Kennedy NA, et al (2020). DOP28 Understanding the molecular mechanisms of anti-TNF treatment failure in patients with Crohn’s disease: a pilot serum proteomic analysis of the PANTS cohort. Journal of Crohn's and Colitis, 14(Supplement_1), s067-s068.
Gordon C, Chee D, Hamilton B, Chanchlani N, Heerasing NM, Hendy P, Lin S, Wesley E, Daniels I, Goodhand JR, et al (2020). P250 Root cause analysis to identify missed opportunities for the diagnosis of colorectal cancer in inflammatory bowel disease. Journal of Crohn's and Colitis, 14(Supplement_1), s273-s275.
Walker GJ, Chanchlani N, Thomas A, Lin S, Moore L, Heerasing NM, Hendy P, Abdelrahim M, Mole S, Perry MH, et al (2020). Primary care faecal calprotectin testing in children with suspected inflammatory bowel disease: a diagnostic accuracy study.
Arch Dis Child,
105(10), 957-963.
Abstract:
Primary care faecal calprotectin testing in children with suspected inflammatory bowel disease: a diagnostic accuracy study.
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 the Royal Devon and Exeter NHS Foundation Trust in the South-West of England, UK. PATIENTS: 195 children aged between 4 and 18 years referred on the pathway between January 2014 and August 2017 for investigation of gastrointestinal symptoms were included. INTERVENTIONS: Primary-care-driven faecal calprotectin testing. Primary and secondary care records over 12 months from the point of calprotectin testing were used as the reference standard. MAIN OUTCOME MEASURES: Diagnostic accuracy of calprotectin testing to detect IBD. RESULTS: 7% (13/195) tested patients were diagnosed with IBD. Using our prespecified cut-off of 100 µg/g, calprotectin had a diagnostic accuracy of 91% (95% CI 86% to 95%) with a sensitivity for distinguishing IBD from non-IBD of 100% (95% CI 75% to 100%), a specificity of 91% (95% CI 85% to 94%), a positive predictive value of 43% (95% CI 25% to 63%) and a negative predictive value of 100% (95% CI 98% to 100%). Calprotectin testing had no effect on the time to diagnosis, but a negative test contributed to saved referrals and was associated with fewer diagnostic tests in secondary care. CONCLUSIONS: Calprotectin testing of children with suspected IBD in primary care accurately distinguishes IBD from a functional gut disorder, reduces secondary care referrals and associated diagnostic healthcare utilisation.
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Author URL.
Walker GJ, Lin S, Chanchlani N, Thomas A, Hendy P, Heerasing N, Moore L, Green HD, Chee D, Bewshea C, et al (2020). Quality improvement project identifies factors associated with delay in IBD diagnosis.
Alimentary Pharmacology & Therapeutics,
52(3), 471-480.
Abstract:
Quality improvement project identifies factors associated with delay in IBD diagnosis
SummaryBackgroundDelay in the diagnosis of inflammatory bowel disease (IBD) is common and contemporary UK studies are lacking.AimTo determine factors associated with, and the consequences of, a prolonged time to diagnosis in IBD.MethodsThis quality improvement study included 304 adults with a new IBD diagnosis made between January 2014 and December 2017 across 49 general practices (GP) and gastroenterology secondary care services. Outcome measures were demographic, clinical and laboratory factors associated with a delayed time, defined as greater than upper quartile, to: (a) patient presentation (b) GP referral (c) secondary care diagnosis, and factors associated with a complicated disease course (hospitalisation and/or surgery and/or biologic treatment) in the year after diagnosis.ResultsThe median [IQR] diagnosis sub‐intervals were: (a) patient = 2.1 months [0.9‐5.1]; (b) GP = 0.3 months [0.0‐0.9]; (c) secondary care = 1.1 months [0.5‐2.1]. 50% of patients were diagnosed within 4 months and 92% were diagnosed within 2 years of symptom onset. Diagnostic delay was more common in Crohn's disease (7.6 months [3.1‐15.0]) than ulcerative colitis (3.3 months [1.9‐7.3]) (P < 0.001). Patients who presented as an emergency (P < 0.001) but not those with a delayed overall time to diagnosis (P = 0.35) were more likely to have a complicated disease course.ConclusionTime to patient presentation is the largest component of time to IBD diagnosis. Emergency presentation is common and, unlike a delayed time to diagnosis, is associated with a complicated disease course.
Abstract.
Gordon C, Chee D, Hamilton B, Chanchlani N, Heerasing NM, Hendy P, Lin S, Wesley E, Daniels I, Goodhand JR, et al (2020). Root cause analysis to identify missed opportunities for the diagnosis of colorectal cancer in inflammatory bowel disease.
JOURNAL OF CROHNS & COLITIS,
14, S273-S275.
Author URL.
Bewshea CM, Ahmad T, Kennedy N, Goodhand J, McDonald T, Green H (2019). Predictors of anti-TNF treatment failure in anti-TNF-naive patients with active luminal Crohn's disease: a prospective, multicentre, cohort study. Lancet Gastroenterology and Hepatology
Lin S, Sanders DS, Gleeson JT, Osborne C, Messham L, Kurien M (2016). Long-term outcomes in patients diagnosed with bile-acid diarrhoea. European Journal of Gastroenterology & Hepatology, 28(2), 240-245.
Lin S, Kurien M, Aziz I, Winfield S, Rugg N, Kelsall A, Leeds JS, Sanders DS (2013). PTU-134 Prevalance and Investigational Pathways of Patients with Constipation Predominant Irritable Bowel Syndrome. Gut, 62(Suppl 1).
Ibrahim W, Lin S (2013). Reducing time spent by junior doctors on call performing routine tasks at weekends. BMJ Open Quality, 2(1).
Lin S, Kurien M, Leeds JS, Sanders DS (2012). PWE-056 Prospective evaluation of 403 patients with diarrhoea predominant irritable bowel syndrome (D-IBS) fulfilling Rome II criteria. Gut, 61(Suppl 2).
Barratt SM, Leeds JS, Lin S, Wilson H, Sanders DS (2010). PTH-084 Gluten-free diet adherent: but at what cost?. Gut, 59(Suppl 1).
Barratt SM, Leeds JS, Lobo AJ, Mcalindon ME, Robinson K, Wilson H, Lin S, Sanders DS (2010). PWE-025 Comparing quality of life in coeliac disease and inflammatory bowel disease: a paradigm shift in our perceptions?. Gut, 59(Suppl 1).
Conferences
Lin S, Bewshea C, Chanchlani N, Chee D, Pollok RC, Kennedy NA, Ahmad T, Goodhand JR (2021). Depression in biologic-treated patients with inflammatory bowel disease during the COVID19 pandemic.
Author URL.
Chee D, Hamilton B, Cairnes V, Lin S, Chanchlani N, Ahmad T, Goodhand J, Kennedy N (2021). Development of a new Inflammatory Bowel Disease Patient Identifier shortens time to clinic review and initiation of treatment.
Author URL.
Chanchlani N, Lin S, Thomas A, Hamilton B, Nice R, Chee D, Kennedy N, Goodhand J, Ahmad T, Investigators IMSATS, et al (2021). Immunogenicity to second anti-TNF therapy (IMSAT): Implications for sequencing of biologic therapy.
Author URL.
Windak H, Cairnes V, Chanchlani N, Chee D, Hamilton B, Heerasing N, Hendy P, Lin S, Kennedy N, Goodhand J, et al (2021). OUTCOMES OF GP OUTREACH PROGRAMME OFFERING COLONOSCOPIC SURVEILLANCE FOR IBD PATIENTS MANAGED IN PRIMARY CARE.
Author URL.
Nice R, Chanchlani N, Kennedy NA, Green HD, Lin S, Gordon C, Chee D, Hamilton B, Bewshea C, Goodhand J, et al (2021). POSITIVITY THRESHOLDS OF TOTAL INFLIXIMAB AND ADALIMUMAB ANTI-DRUG ANTIBODY ASSAYS AND IMPACT IN CLINICAL PRACTICE.
Author URL.
Walker G, Lin S, Thomas A, Chanchlani N, Moore L, Hendy P, Heerasing N, Green H, Mole S, Bewshea C, et al (2019). PROSPECTIVE COHORT TO IDENTIFY FACTORS ASSOCIATED WITH DIAGNOSTIC DELAY IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE.
Author URL.
Walker G, Lin S, Chanchlani N, Thomas A, Moore L, Hendy P, Heerasing N, Green H, Bewshea C, Goodhand J, et al (2019). Prospective cohort to identify factors associated with a delay in diagnosis in patients with inflammatory bowel disease.
Author URL.
Publications by year
2023
Hanić M, Vučković F, Deriš H, Bewshea C, Lin S, Goodhand JR, Ahmad T, Trbojević-Akmačić I, Kennedy NA, Lauc G, et al (2023). Anti-TNF Biologicals Enhance the Anti-Inflammatory Properties of IgG N-Glycome in Crohn’s Disease.
Biomolecules,
13(6), 954-954.
Abstract:
Anti-TNF Biologicals Enhance the Anti-Inflammatory Properties of IgG N-Glycome in Crohn’s Disease
Crohn’s disease (CD) is a chronic inflammation of the digestive tract that significantly impairs patients’ quality of life and well-being. Anti-TNF biologicals revolutionised the treatment of CD, yet many patients do not adequately respond to such therapy. Previous studies have demonstrated a pro-inflammatory pattern in the composition of CD patients’ immunoglobulin G (IgG) N-glycome compared to healthy individuals. Here, we utilised the high-throughput UHPLC method for N-glycan analysis to explore the longitudinal effect of the anti-TNF drugs infliximab and adalimumab on N-glycome composition of total serum IgG in 198 patients, as well as the predictive potential of IgG N-glycans at baseline to detect primary non-responders to anti-TNF therapy in 1315 patients. We discovered a significant decrease in IgG agalactosylation and an increase in monogalactosylation, digalactosylation and sialylation during the 14 weeks of anti-TNF treatment, regardless of therapy response, all of which suggested a diminished inflammatory environment in CD patients treated with anti-TNF therapy. Furthermore, we observed that IgG N-glycome might contain certain information regarding the anti-TNF therapy outcome before initiating the treatment. However, it is impossible to predict future primary non-responders to anti-TNF therapy based solely on IgG N-glycome composition at baseline.
Abstract.
Lin S, Hannon E, Waring JF, Reppell M, Smaoui N, Pivorunas VL, Guay H, Chanchlani N, Bewshea C, Bai BYH, et al (2023). DOP88 Understanding the molecular mechanisms of anti-TNF treatment failure: Whole blood DNA methylation changes associated with primary non-response to anti-TNF treatment in patients with Crohn’s disease. Journal of Crohn's and Colitis, 17(Supplement_1), i164-i166.
Liu Z, Le K, Zhou X, Alexander JL, Lin S, Bewshea C, Chanchlani N, Nice R, McDonald TJ, Lamb CA, et al (2023). Neutralising antibody potency against SARS-CoV-2 wild-type and omicron BA.1 and BA.4/5 variants in patients with inflammatory bowel disease treated with infliximab and vedolizumab after three doses of COVID-19 vaccine (CLARITY IBD): an analysis of a prospective multicentre cohort study.
Lancet Gastroenterol Hepatol,
8(2), 145-156.
Abstract:
Neutralising antibody potency against SARS-CoV-2 wild-type and omicron BA.1 and BA.4/5 variants in patients with inflammatory bowel disease treated with infliximab and vedolizumab after three doses of COVID-19 vaccine (CLARITY IBD): an analysis of a prospective multicentre cohort study.
BACKGROUND: Anti-TNF drugs, such as infliximab, are associated with attenuated antibody responses after SARS-CoV-2 vaccination. We aimed to determine how the anti-TNF drug infliximab and the anti-integrin drug vedolizumab affect vaccine-induced neutralising antibodies against highly transmissible omicron (B.1.1.529) BA.1, and BA.4 and BA.5 (hereafter BA.4/5) SARS-CoV-2 variants, which possess the ability to evade host immunity and, together with emerging sublineages, are now the dominating variants causing current waves of infection. METHODS: CLARITY IBD is a prospective, multicentre, observational cohort study investigating the effect of infliximab and vedolizumab on SARS-CoV-2 infection and vaccination in patients with inflammatory bowel disease (IBD). Patients aged 5 years and older with a diagnosis of IBD and being treated with infliximab or vedolizumab for 6 weeks or longer were recruited from infusion units at 92 hospitals in the UK. In this analysis, we included participants who had received uninterrupted biological therapy since recruitment and without a previous SARS-CoV-2 infection. The primary outcome was neutralising antibody responses against SARS-CoV-2 wild-type and omicron subvariants BA.1 and BA.4/5 after three doses of SARS-CoV-2 vaccine. We constructed Cox proportional hazards models to investigate the risk of breakthrough infection in relation to neutralising antibody titres. The study is registered with the ISRCTN registry, ISRCTN45176516, and is closed to accrual. FINDINGS: Between Sept 22 and Dec 23, 2020, 7224 patients with IBD were recruited to the CLARITY IBD study, of whom 1288 had no previous SARS-CoV-2 infection after three doses of SARS-CoV-2 vaccine and were established on either infliximab (n=871) or vedolizumab (n=417) and included in this study (median age was 46·1 years [IQR 33·6-58·2], 610 [47·4%] were female, 671 [52·1%] were male, 1209 [93·9%] were White, and 46 [3·6%] were Asian). After three doses of SARS-CoV-2 vaccine, 50% neutralising titres (NT50s) were significantly lower in patients treated with infliximab than in those treated with vedolizumab, against wild-type (geometric mean 2062 [95% CI 1720-2473] vs 3440 [2939-4026]; p
Abstract.
Author URL.
Liu Z, Le K, Zhou X, Alexander J, Lin S, Bewshea C, Chanchlani N, Nice R, McDonald T, Lamb C, et al (2023). OP24 Neutralising antibody potency against SARS-CoV-2 wild-type and Omicron BA.1 and BA.4/5 variants in infliximab and vedolizumab treated patients with Inflammatory Bowel Disease after three doses of COVID-19 vaccine: a prospective multicentre cohort study. Journal of Crohn's and Colitis, 17(Supplement_1), i32-i34.
Carbery I, Lin S, Chanchlani N, Janjua M, Nice R, McDonald TJ, Bewshea C, Kennedy NA, Ahmad T, Goodhand JR, et al (2023). P649 Does serum triiodothyronine-to-thyroxine (T3/T4) ratio predict therapeutic outcome to anti-TNF therapies in biologic-naïve patients with active luminal Crohn’s disease?. Journal of Crohn's and Colitis, 17(Supplement_1), i778-i778.
Lin S, Chanchlani N, Smith R, Roberts C, Nice R, McDonald TJ, Hamilton B, Bewshea C, Kennedy NA, Goodhand JR, et al (2023). P662 Pre-treatment vitamin D concentrations do not predict therapeutic outcome to anti-TNF therapies in biologic-naïve patients with active luminal Crohn’s disease. Journal of Crohn's and Colitis, 17(Supplement_1), i791-i793.
Chanchlani N, Lin S, Hamilton B, Bewshea C, Thomas A, Smith R, Roberts C, Nice R, McDonald TJ, Goodhand JR, et al (2023). P798 Understanding anti-TNF treatment failure: mechanisms and management of loss of response to anti-TNF therapy, three-year data from the PANTS study. Journal of Crohn's and Colitis, 17(Supplement_1), i928-i930.
2022
Chanchlani N, Lin S, Chee D, Hamilton B, Nice R, Arkir Z, Bewshea C, Cipriano B, Derikx LAAP, Dunlop A, et al (2022). Adalimumab and Infliximab Impair SARS-CoV-2 Antibody Responses: Results from a Therapeutic Drug Monitoring Study in 11 422 Biologic-Treated Patients.
J Crohns Colitis,
16(3), 389-397.
Abstract:
Adalimumab and Infliximab Impair SARS-CoV-2 Antibody Responses: Results from a Therapeutic Drug Monitoring Study in 11 422 Biologic-Treated Patients.
BACKGROUND AND AIMS: Infliximab attenuates serological responses to SARS-CoV-2 infection. Whether this is a class effect, or if anti-tumour necrosis factor [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 11 422 (53.3% [6084] male; median age 36.8 years) patients with immune-mediated inflammatory diseases, stored at six therapeutic drug monitoring laboratories between January 29 and September 30, 2020. Data were linked to nationally held SARS-CoV-2 PCR results to July 11, 2021. RESULTS: Rates of PCR-confirmed SARS-CoV-2 infection were similar across treatment groups. Seroprevalence rates were lower in infliximab- and adalimumab- than vedolizumab-treated patients (infliximab: 3.0% [178/5893], adalimumab: 3.0% [152/5074], vedolizumab: 6.7% [25/375], p
=
0.003). The magnitude of SARS-CoV-2 reactivity was similar in infliximab- vs adalimumab-treated patients (median 4.30 cut-off index [COI] [1.94-9.96] vs 5.02 [2.18-18.70], p
=
0.164), but higher in vedolizumab-treated patients (median 21.60 COI [4.39-68.10, p
Abstract.
Author URL.
Lin S, Kennedy NA, Saifuddin A, Sandoval DM, Reynolds CJ, Seoane RC, Kottoor SH, Pieper FP, Lin K-M, Butler DK, et al (2022). Antibody decay, T cell immunity and breakthrough infections following two SARS-CoV-2 vaccine doses in inflammatory bowel disease patients treated with infliximab and vedolizumab.
Nat Commun,
13(1).
Abstract:
Antibody decay, T cell immunity and breakthrough infections following two SARS-CoV-2 vaccine doses in inflammatory bowel disease patients treated with infliximab and vedolizumab.
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 antibody, infliximab, or with vedolizumab targeting a gut-specific anti-integrin that does not impair systemic immunity. Geometric mean [SD] anti-S RBD antibody concentrations are lower and half-lives shorter in patients treated with infliximab than vedolizumab, following two doses of BNT162b2 (566.7 U/mL [6.2] vs 4555.3 U/mL [5.4], p
Abstract.
Author URL.
Chee D, Nice R, Hamilton B, Jones E, Hawkins S, Redstone C, Cairnes V, Pohl K, Chanchlani N, Lin S, et al (2022). Patient-led Remote IntraCapillary pharmacoKinetic Sampling (fingerPRICKS) for Therapeutic Drug Monitoring in patients with Inflammatory Bowel Disease.
J Crohns Colitis,
16(2), 190-198.
Abstract:
Patient-led Remote IntraCapillary pharmacoKinetic Sampling (fingerPRICKS) for Therapeutic Drug Monitoring in patients with Inflammatory Bowel Disease.
BACKGROUND AND 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 blood sampling can be undertaken by patients at home and samples returned by post to central laboratories. We sought to report the effect of the COVID-19 pandemic on requests for therapeutic drug monitoring and the equivalence, acceptability and effectiveness of low volume Patient-led Remote IntraCapillary pharmacoKinetic Sampling [fingerPRICKS] compared to conventional venepuncture. METHODS: We undertook a cross-sectional blood sampling methods comparison study and compared sample types using linear regression models. Drug and antidrug antibody levels were measured using standard ELISAs. Acceptability was assessed using a purpose-designed questionnaire. RESULTS: Therapeutic drug monitoring requests for adalimumab (96.5 [70.5-106] per week to 52 [33.5-57.0], p < 0.001) but not infliximab (184.5 [161.2-214.2] to 161 [135-197.5], p = 0.34) reduced during the first UK stay-at-home lockdown compared with the preceding 6 months. Fingerprick sampling was equivalent to conventional venepuncture for adalimumab, infliximab, vedolizumab and ustekinumab drug, and anti-adalimumab and anti-infliximab antibody levels. The median [interquartile range] volume of serum obtained using intracapillary sampling was 195 µL [130-210]. More than 87% [90/103] of patients agreed that intracapillary testing was easy and 69% [71/103] preferred it to conventional venepuncture. In routine care, 75.3% [58/77] of patients returned two blood samples within 14 days to permit remote assessment of biologic therapeutic drug monitoring. CONCLUSIONS: Therapeutic drug monitoring can be undertaken using patient-led remote intracapillary blood sampling and has the potential to be a key adjunct to telemedicine in patients with immune-mediated inflammatory diseases.
Abstract.
Author URL.
2021
Kennedy NA, Goodhand JR, Bewshea C, Nice R, Chee D, Lin S, Chanchlani N, Butterworth J, Cooney R, Croft NM, et al (2021). Anti-SARS-CoV-2 antibody responses are attenuated in patients with IBD treated with infliximab.
Gut,
70(5), 865-875.
Abstract:
Anti-SARS-CoV-2 antibody responses are attenuated in patients with IBD treated with infliximab
ObjectiveAntitumour 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.DesignAntibody responses in participants treated with infliximab were compared with a reference cohort treated with vedolizumab, a gut-selective anti-integrin α4β7 monoclonal antibody that is not associated with impaired vaccine responses or increased susceptibility to systemic infections. 6935 patients were recruited from 92 UK hospitals between 22 September and 23 December 2020.ResultsRates of symptomatic and proven SARS-CoV-2 infection were similar between groups. Seroprevalence was lower in infliximab-treated than vedolizumab-treated patients (3.4% (161/4685) vs 6.0% (134/2250), p<0.0001). Multivariable logistic regression analyses confirmed that infliximab (vs vedolizumab; OR 0.66 (95% CI 0.51 to 0.87), p=0.0027) and immunomodulator use (OR 0.70 (95% CI 0.53 to 0.92), p=0.012) were independently associated with lower seropositivity. In patients with confirmed SARS-CoV-2 infection, seroconversion was observed in fewer infliximab-treated than vedolizumab-treated patients (48% (39/81) vs 83% (30/36), p=0.00044) and the magnitude of anti-SARS-CoV-2 reactivity was lower (median 0.8 cut-off index (0.2–5.6) vs 37.0 (15.2–76.1), p<0.0001).ConclusionsInfliximab is associated with attenuated serological responses to SARS-CoV-2 that were further blunted by immunomodulators used as concomitant therapy. Impaired serological responses to SARS-CoV-2 infection might have important implications for global public health policy and individual anti-TNF-treated patients. Serological testing and virus surveillance should be considered to detect suboptimal vaccine responses, persistent infection and viral evolution to inform public health policy.Trial registration numberISRCTN45176516.
Abstract.
Lin S, Kennedy NA, Saifuddin A, Sandoval DM, Reynolds CJ, Seoane RC, Kottoor SH, Pieper FP, Lin K-M, Butler DK, et al (2021). Antibody decay, T cell immunity and breakthrough infections following two SARS-CoV-2 vaccine doses in infliximab- and vedolizumab-treated patients.
Lin S, Bewshea C, Chanchlani N, Chee D, Pollok RC, Kennedy NA, Ahmad T, Goodhand JR (2021). Depression in biologic-treated patients with inflammatory bowel disease during the COVID19 pandemic.
Author URL.
Chee D, Hamilton B, Cairnes V, Lin S, Chanchlani N, Ahmad T, Goodhand J, Kennedy N (2021). Development of a new Inflammatory Bowel Disease Patient Identifier shortens time to clinic review and initiation of treatment.
Author URL.
Chanchlani N, Lin S, Thomas A, Hamilton B, Nice R, Chee D, Kennedy N, Goodhand J, Ahmad T (2021). HMO-4 Immunogenicity to second anti-TNF therapy (IMSAT): implications for sequencing of biologic therapy. Gut, 70(Suppl 4), a31-a32.
Chanchlani N, Lin S, Thomas A, Hamilton B, Nice R, Chee D, Kennedy N, Goodhand J, Ahmad T, Investigators IMSATS, et al (2021). Immunogenicity to second anti-TNF therapy (IMSAT): Implications for sequencing of biologic therapy.
Author URL.
Kennedy NA, Lin S, Goodhand JR, Chanchlani N, Hamilton B, Bewshea C, Nice R, Chee D, Cummings F, Fraser A, et al (2021). Infliximab is associated with attenuated immunogenicity to BNT162b2 and ChAdOx1 nCoV-19 SARS-CoV-2 vaccines.
Kennedy NA, Lin S, Goodhand JR, Chanchlani N, Hamilton B, Bewshea C, Nice R, Chee D, Cummings JF, Fraser A, et al (2021). Infliximab is associated with attenuated immunogenicity to BNT162b2 and ChAdOx1 nCoV-19 SARS-CoV-2 vaccines in patients with IBD.
Gut,
70(10), 1884-1893.
Abstract:
Infliximab is associated with attenuated immunogenicity to BNT162b2 and ChAdOx1 nCoV-19 SARS-CoV-2 vaccines in patients with IBD.
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 seroconversion rates in infliximab-treated patients (n=865) were compared with a cohort treated with vedolizumab (n=428), a gut-selective anti-integrin α4β7 monoclonal antibody. Our primary outcome was anti-SARS-CoV-2 spike (S) antibody concentrations, measured using the Elecsys anti-SARS-CoV-2 spike (S) antibody assay 3-10 weeks after vaccination, in patients without evidence of prior infection. Secondary outcomes were seroconversion rates (defined by a cut-off of 15 U/mL), and antibody responses following past infection or a second dose of the BNT162b2 vaccine. RESULTS: Geometric mean (SD) anti-SARS-CoV-2 antibody concentrations were lower in patients treated with infliximab than vedolizumab, following BNT162b2 (6.0 U/mL (5.9) vs 28.8 U/mL (5.4) p
Abstract.
Author URL.
Kennedy N, Lin S, Goodhand J, Powell N, Ahmad T, group CIS (2021). OFR-8 Infliximab is associated with attenuated immunogenicity to BNT162b2 and ChAdOx1 nCoV-19 SARS-CoV-2 vaccines. Gut, 70(Suppl 4), a3-a4.
Windak H, Cairnes V, Chanchlani N, Chee D, Hamilton B, Heerasing N, Hendy P, Lin S, Kennedy N, Goodhand J, et al (2021). OUTCOMES OF GP OUTREACH PROGRAMME OFFERING COLONOSCOPIC SURVEILLANCE FOR IBD PATIENTS MANAGED IN PRIMARY CARE.
Author URL.
Nice R, Chanchlani N, Kennedy NA, Green HD, Lin S, Gordon C, Chee D, Hamilton B, Bewshea C, Goodhand J, et al (2021). POSITIVITY THRESHOLDS OF TOTAL INFLIXIMAB AND ADALIMUMAB ANTI-DRUG ANTIBODY ASSAYS AND IMPACT IN CLINICAL PRACTICE.
Author URL.
2020
Lin S, Green HD, Hendy P, Heerasing NM, Chanchlani N, Hamilton B, Walker GJ, Heap GA, Hobart J, Martin RJ, et al (2020). Clinical Features and Genetic Risk of Demyelination Following Anti-TNF Treatment.
J Crohns Colitis,
14(12), 1653-1661.
Abstract:
Clinical Features and Genetic Risk of Demyelination Following Anti-TNF Treatment.
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 to test whether affected patients were genetically predisposed to multiple sclerosis [MS]. METHODS: We conducted a case-control study to describe the clinical features of demyelination events following anti-TNF exposure. We compared genetic risk scores [GRS], calculated using carriage of 43 susceptibility loci for MS, in 48 cases with 1219 patients exposed to anti-TNF who did not develop demyelination. RESULTS: Overall, 39 [74%] cases were female. The median age [range] of patients at time of demyelination was 41.5 years [20.7-63.2]. The median duration of anti-TNF treatment was 21.3 months [0.5-99.4] and 19 [36%] patients were receiving concomitant immunomodulators. Most patients had central demyelination affecting the brain, spinal cord, or both. Complete recovery was reported in 12 [23%] patients after a median time of 6.8 months [0.1-28.7]. After 33.0 months of follow-up, partial recovery was observed in 29 [55%] patients, relapsing and remitting episodes in nine [17%], progressive symptoms in three [6%]: two [4%] patients were diagnosed with MS. There was no significant difference between MS GRS scores in cases (mean -3.5 × 10-4, standard deviation [SD] 0.0039) and controls [mean -1.1 × 10-3, SD 0.0042] [p = 0.23]. CONCLUSIONS: Patients who experienced demyelination events following anti-TNF exposure were more likely female, less frequently treated with an immunomodulator, and had a similar genetic risk to anti-TNF exposed controls who did not experience demyelination events. Large prospective studies with pre-treatment neuroimaging are required to identify genetic susceptibility loci.
Abstract.
Author URL.
Lin S, Chanchlani N, Invergo BM, Anderson MW, Guay HM, Reppell M, Butler JW, Goodhand JR, Ahmad T, Kennedy NA, et al (2020). DOP28 Understanding the molecular mechanisms of anti-TNF treatment failure in patients with Crohn’s disease: a pilot serum proteomic analysis of the PANTS cohort. Journal of Crohn's and Colitis, 14(Supplement_1), s067-s068.
Gordon C, Chee D, Hamilton B, Chanchlani N, Heerasing NM, Hendy P, Lin S, Wesley E, Daniels I, Goodhand JR, et al (2020). P250 Root cause analysis to identify missed opportunities for the diagnosis of colorectal cancer in inflammatory bowel disease. Journal of Crohn's and Colitis, 14(Supplement_1), s273-s275.
Walker GJ, Chanchlani N, Thomas A, Lin S, Moore L, Heerasing NM, Hendy P, Abdelrahim M, Mole S, Perry MH, et al (2020). Primary care faecal calprotectin testing in children with suspected inflammatory bowel disease: a diagnostic accuracy study.
Arch Dis Child,
105(10), 957-963.
Abstract:
Primary care faecal calprotectin testing in children with suspected inflammatory bowel disease: a diagnostic accuracy study.
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 the Royal Devon and Exeter NHS Foundation Trust in the South-West of England, UK. PATIENTS: 195 children aged between 4 and 18 years referred on the pathway between January 2014 and August 2017 for investigation of gastrointestinal symptoms were included. INTERVENTIONS: Primary-care-driven faecal calprotectin testing. Primary and secondary care records over 12 months from the point of calprotectin testing were used as the reference standard. MAIN OUTCOME MEASURES: Diagnostic accuracy of calprotectin testing to detect IBD. RESULTS: 7% (13/195) tested patients were diagnosed with IBD. Using our prespecified cut-off of 100 µg/g, calprotectin had a diagnostic accuracy of 91% (95% CI 86% to 95%) with a sensitivity for distinguishing IBD from non-IBD of 100% (95% CI 75% to 100%), a specificity of 91% (95% CI 85% to 94%), a positive predictive value of 43% (95% CI 25% to 63%) and a negative predictive value of 100% (95% CI 98% to 100%). Calprotectin testing had no effect on the time to diagnosis, but a negative test contributed to saved referrals and was associated with fewer diagnostic tests in secondary care. CONCLUSIONS: Calprotectin testing of children with suspected IBD in primary care accurately distinguishes IBD from a functional gut disorder, reduces secondary care referrals and associated diagnostic healthcare utilisation.
Abstract.
Author URL.
Walker GJ, Lin S, Chanchlani N, Thomas A, Hendy P, Heerasing N, Moore L, Green HD, Chee D, Bewshea C, et al (2020). Quality improvement project identifies factors associated with delay in IBD diagnosis.
Alimentary Pharmacology & Therapeutics,
52(3), 471-480.
Abstract:
Quality improvement project identifies factors associated with delay in IBD diagnosis
SummaryBackgroundDelay in the diagnosis of inflammatory bowel disease (IBD) is common and contemporary UK studies are lacking.AimTo determine factors associated with, and the consequences of, a prolonged time to diagnosis in IBD.MethodsThis quality improvement study included 304 adults with a new IBD diagnosis made between January 2014 and December 2017 across 49 general practices (GP) and gastroenterology secondary care services. Outcome measures were demographic, clinical and laboratory factors associated with a delayed time, defined as greater than upper quartile, to: (a) patient presentation (b) GP referral (c) secondary care diagnosis, and factors associated with a complicated disease course (hospitalisation and/or surgery and/or biologic treatment) in the year after diagnosis.ResultsThe median [IQR] diagnosis sub‐intervals were: (a) patient = 2.1 months [0.9‐5.1]; (b) GP = 0.3 months [0.0‐0.9]; (c) secondary care = 1.1 months [0.5‐2.1]. 50% of patients were diagnosed within 4 months and 92% were diagnosed within 2 years of symptom onset. Diagnostic delay was more common in Crohn's disease (7.6 months [3.1‐15.0]) than ulcerative colitis (3.3 months [1.9‐7.3]) (P < 0.001). Patients who presented as an emergency (P < 0.001) but not those with a delayed overall time to diagnosis (P = 0.35) were more likely to have a complicated disease course.ConclusionTime to patient presentation is the largest component of time to IBD diagnosis. Emergency presentation is common and, unlike a delayed time to diagnosis, is associated with a complicated disease course.
Abstract.
Gordon C, Chee D, Hamilton B, Chanchlani N, Heerasing NM, Hendy P, Lin S, Wesley E, Daniels I, Goodhand JR, et al (2020). Root cause analysis to identify missed opportunities for the diagnosis of colorectal cancer in inflammatory bowel disease.
JOURNAL OF CROHNS & COLITIS,
14, S273-S275.
Author URL.
2019
Walker G, Lin S, Thomas A, Chanchlani N, Moore L, Hendy P, Heerasing N, Green H, Mole S, Bewshea C, et al (2019). PROSPECTIVE COHORT TO IDENTIFY FACTORS ASSOCIATED WITH DIAGNOSTIC DELAY IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE.
Author URL.
Bewshea CM, Ahmad T, Kennedy N, Goodhand J, McDonald T, Green H (2019). Predictors of anti-TNF treatment failure in anti-TNF-naive patients with active luminal Crohn's disease: a prospective, multicentre, cohort study. Lancet Gastroenterology and Hepatology
Walker G, Lin S, Chanchlani N, Thomas A, Moore L, Hendy P, Heerasing N, Green H, Bewshea C, Goodhand J, et al (2019). Prospective cohort to identify factors associated with a delay in diagnosis in patients with inflammatory bowel disease.
Author URL.
2016
Lin S, Sanders DS, Gleeson JT, Osborne C, Messham L, Kurien M (2016). Long-term outcomes in patients diagnosed with bile-acid diarrhoea. European Journal of Gastroenterology & Hepatology, 28(2), 240-245.
2013
Lin S, Kurien M, Aziz I, Winfield S, Rugg N, Kelsall A, Leeds JS, Sanders DS (2013). PTU-134 Prevalance and Investigational Pathways of Patients with Constipation Predominant Irritable Bowel Syndrome. Gut, 62(Suppl 1).
Ibrahim W, Lin S (2013). Reducing time spent by junior doctors on call performing routine tasks at weekends. BMJ Open Quality, 2(1).
2012
Lin S, Kurien M, Leeds JS, Sanders DS (2012). PWE-056 Prospective evaluation of 403 patients with diarrhoea predominant irritable bowel syndrome (D-IBS) fulfilling Rome II criteria. Gut, 61(Suppl 2).
2010
Barratt SM, Leeds JS, Lin S, Wilson H, Sanders DS (2010). PTH-084 Gluten-free diet adherent: but at what cost?. Gut, 59(Suppl 1).
Barratt SM, Leeds JS, Lobo AJ, Mcalindon ME, Robinson K, Wilson H, Lin S, Sanders DS (2010). PWE-025 Comparing quality of life in coeliac disease and inflammatory bowel disease: a paradigm shift in our perceptions?. Gut, 59(Suppl 1).