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1.
Br Med Bull ; 2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33884410

RESUMO

INTRODUCTION: The aim of treatment in inflammatory bowel disease (IBD) is to control symptoms and suppress gut inflammation with minimal systemic side effects. A large proportion of patients are either primary non-responders or lose response to currently licensed therapies. The development of monoclonal antibodies, blocking interleukin (IL)-12 and IL-23 pathways are a promising therapeutic advance. We review the data on IL12/23 inhibitors and emerging data on IL-23 inhibition in IBD treatment. SOURCES OF DATA: This review is based on data published in peer-reviewed journals and clinical trials registry. AREAS OF AGREEMENT: Ustekinumab is currently approved for managing corticosteroid and biologic refractory IBD patients with a favourable safety profile. AREAS OF CONTROVERSY: Despite a growing therapeutic armamentarium and convergence on the role of biological therapies in patients with greater disease severity, there remains considerable uncertainty with selection and positioning of treatment. GROWING POINTS: Efficacy data from clinical trials and a growing body of real-world data have established a role for IL12/23 inhibitor Ustekinumab in IBD. There is resurgent interest in IL-23 specificity and the potential for incremental benefit. The potential for IL-22 to act as a biomarker for IL-23 inhibitors has exciting implications for personalized medicine. AREAS TIMELY FOR DEVELOPING RESEARCH: Head-to-head trials exploring efficacy and combination with other biologics with the potential for synergistic benefit are under investigation. Results of phase 3 trials with IL-23 inhibitors incorporating clinical, biochemical and endoscopic parameters and also exploring biomarkers as predictors of response are urgently needed.

3.
Gut ; 70(5): 865-875, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33753421

RESUMO

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: Antibody responses in participants treated with infliximab were compared with a reference cohort treated with vedolizumab, a gut-selective anti-integrin α4ß7 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. RESULTS: Rates 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). CONCLUSIONS: Infliximab 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 NUMBER: ISRCTN45176516.


Assuntos
Anticorpos Antivirais/imunologia , Formação de Anticorpos/imunologia , Fármacos Gastrointestinais/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab/uso terapêutico , /imunologia , Adulto , Anticorpos Monoclonais Humanizados/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Testes Sorológicos , Reino Unido/epidemiologia
5.
Intest Res ; 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33396977

RESUMO

Background/Aims: Epidemiological associations have implicated factors associated with Westernization, including the Western diet, in the development of inflammatory bowel disease (IBD). The role of diet in IBD etiopathogenesis, disease control and symptom management remains incompletely understood. Few studies have collected data on the dietary habits of immigrant populations living with IBD. Our aim was to describe the dietary practices and beliefs of British South Asians with IBD. Methods: A 30-item questionnaire was developed and consecutively administered to 255 British South Asians with IBD attending gastroenterology clinics in the United Kingdom. Results: Fifty-one percent of participants believed diet was the initiating factor for their IBD and 63% felt diet had previously triggered disease relapse. Eighty-nine percent avoided certain dietary items in the belief that this would prevent relapse. The most commonly avoided foods and drinks were spicy and fatty foods, carbonated drinks, milk products, alcohol, coffee, and red meat. A third of patients had tried a whole food exclusion diet, most commonly lactose- or gluten-free, and this was most frequently reported amongst those with clinically active IBD (P= 0.02). Almost 60% of participants avoided eating the same menu as their family, or eating out, at least sometimes, to prevent IBD relapse. Conclusions: British South Asians with IBD demonstrate significant dietary beliefs and food avoidance behaviors with increased frequency compared to those reported in Caucasian IBD populations. Studies in immigrant populations may offer valuable insights into the interaction between diet, Westernization and cultural drift in IBD pathogenesis and symptomatology.

6.
World J Gastroenterol ; 26(43): 6710-6769, 2020 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-33268959

RESUMO

Ulcerative colitis and Crohn's disease are the main entities of inflammatory bowel disease characterized by chronic remittent inflammation of the gastrointestinal tract. The incidence and prevalence are on the rise worldwide, and the heterogeneity between patients and within individuals over time is striking. The progressive advance in our understanding of the etiopathogenesis coupled with an unprecedented increase in therapeutic options have changed the management towards evidence-based interventions by clinicians with patients. This guideline was stimulated and supported by the Emirates Gastroenterology and Hepatology Society following a systematic review and a Delphi consensus process that provided evidence- and expert opinion-based recommendations. Comprehensive up-to-date guidance is provided regarding diagnosis, evaluation of disease severity, appropriate and timely use of different investigations, choice of appropriate therapy for induction and remission phase according to disease severity, and management of main complications.

7.
9.
Indian J Gastroenterol ; 39(4): 311-314, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-33017038
10.
Artigo em Inglês | MEDLINE | ID: mdl-32956176

RESUMO

OBJECTIVE: Diet is implicated in the aetiopathogenesis of inflammatory bowel disease (IBD) and in generating symptoms. Few studies have explored dietary practices in people with IBD, in which participants perceived strong links between diet in triggering flares and maintaining remission. Fewer studies have explored dietary habits in self-reported remission. Our aim was to describe dietary practices and beliefs in those with inactive ulcerative colitis. METHODS: A questionnaire was developed and prospectively administered to 208 participants with inactive ulcerative colitis attending IBD clinics. RESULTS: Thirty-one percent believed diet was the initiating factor for ulcerative colitis with 37% believing diet could trigger relapse. Fifty-nine percent avoided dietary items to prevent relapse. Most frequently avoided were spicy (43%) and fatty (38%) foods, alcohol (27%), carbonated drinks (26%), coffee (24%) and milk products (21%). Females were more likely to practice dietary avoidance (P = 0.007). Twenty-three percent had used exclusion diets, most commonly gluten- or lactose-free. Those reporting relapse in the previous year were more likely to avoid the same menu as their family (P = 0.01) and females were less likely to eat out in order to prevent relapse (P = 0.004). Information resources guiding food avoidance included participants' own experiences (90%), healthcare professionals' advice (19%) and the internet (11%). CONCLUSION: People with inactive ulcerative colitis hold dietary beliefs and display practices with a high level of consistency around perceived triggers. Food avoidance whilst in remission raises the possibility of visceral hypersensitivity or altered physiology alongside psychosocial, neurocognitive or co-existing functional factors.

11.
Artigo em Inglês | MEDLINE | ID: mdl-32889976

RESUMO

AIM: The role of anti-tumour necrosis factor (TNF) medications in inflammatory bowel disease (IBD) is now established. Recent studies have reported the incidence of dermatological adverse events with use of anti-TNFs in IBD. The aim of this study was to investigate the incidence of dermatological reactions in patients on anti-TNF therapy for IBD. METHODS: We searched MEDLINE, the Cochrane Library and EMBASE to identify studies reporting any dermatological reaction in patients exposed to anti-TNF for treatment of IBD. The incidence of dermatological complications in the entire review population was pooled by meta-analysis of data from individual studies using the random effects model. Pooled estimates in male and female patients and in patients treated with different anti-TNF agents were also calculated. We applied mixed effects (methods of moments) regression models to investigate between-study heterogeneity. RESULTS: Forty-eight studies reporting a total of 29 776 patients treated with anti-TNF medications for IBD were identified. Gender distribution was available for 18 960 participants with 45.3% females. Data on type of disease were available for 20 226 patients: 74.9% (n = 15 154) Crohn's disease, 24.2% (n = 4901) ulcerative colitis and 0.9% (n = 171) IBD-unclassified. The type of anti-TNF used was mentioned for 17 085 individuals: 67.5% (n = 11 530) infliximab (IFX), 30.5% (n = 5203) adalimumab (ADA), 1.7% (n = 296) certolizumab and 0.3% (n = 56) golimumab. The pooled incidence of any dermatological reaction from 26 studies was 19.4% [95% confidence interval (CI): 15.2-24.4]. The pooled incidence for IFX and ADA was 23.7% (95% CI: 17.8-30.8) from 12 studies and 33.3% (95% CI 18.8-51.1) from seven studies, respectively. We found a trend of increased event rate with increasing percentage of male population (P = 0.08). The commonest reported event (39 studies) was psoriasis/psoriasiform rash with a pooled incidence of 5.6% (95% CI: 4.2-7.4). The incidence of psoriasis/psoriasiform rashes for IFX and ADA was 6.1% (95% CI 3.4-10.6) from 15 studies and 5.9% (95% CI: 2.5-13.5) from seven studies, respectively. Other reactions reported included eczema with a pooled incidence of 5.5% (95% CI: 3.3-8.9) from 17 studies and skin infections with pooled incidence of 7.9% (95% CI: 5.5-11.2) from 11 studies. CONCLUSION: The incidence of dermatological events in patients with IBD treated with anti-TNF medications is high. The most commonly reported reaction is psoriasis/psoriasiform reaction. Clinicians should be vigilant to dermatological side effects following treatment of IBD with anti-TNF.

13.
Indian J Gastroenterol ; 39(2): 176-185, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32483692

RESUMO

BACKGROUND: Evidence supports therapeutic drug monitoring (TDM) in improving efficacy and cost-effectiveness of anti-TNF therapy in inflammatory bowel disease (IBD). Data on perceptions and barriers to TDM use are limited and no data are available from India. Our objective was to assess clinicians' attitudes and barriers to TDM use in IBD. METHODS: A 16-question survey was distributed to members of the Indian Society of Gastroenterology. Information on clinician characteristics, demographics, use and barriers towards TDM with anti-TNFs was collected. Logistic regression was used to predict factors influencing TDM use. RESULTS: Two hundred and forty-two respondents participated (92.5% male); 83% were consultant gastroenterologists. Of 104 respondents meeting inclusion criteria (treating > 5 IBD patients and at least 1 with an anti-TNF per month), complete responses were available for 101 participants. TDM was utilized by 20% (n = 20) of respondents. Of them, 89.5% (n = 17) used TDM for secondary loss of response; 73.7% (n = 14) for primary non-response and 5.3% (n = 1) proactively. Barriers to TDM use were cost (71.2%), availability (67.8%), time lag in results (58.7%) and the perception that TDM is time-consuming (45.7%). Clinicians treating > 30 IBD patients were more likely to check TDM (OR = 4.9, p = 0.02). Of 81 respondents not using TDM, 97.5% (n = 79) would do so if all the barriers were removed. CONCLUSION: Significant barriers to TDM use were availability, cost and time lag for results. If these barriers were removed, almost all the clinicians would use TDM at least reactively and 25% would use proactively. There is an urgent need to address these barriers and optimize anti-TNF therapy for optimal outcomes.


Assuntos
Monitoramento de Medicamentos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab/uso terapêutico , Utilização de Procedimentos e Técnicas/estatística & dados numéricos , Inquéritos e Questionários , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Adulto , Idoso , Análise Custo-Benefício , Monitoramento de Medicamentos/estatística & dados numéricos , Feminino , Humanos , Índia/epidemiologia , Doenças Inflamatórias Intestinais/economia , Infliximab/economia , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Inibidores do Fator de Necrose Tumoral/economia
14.
Gut ; 69(10): 1769-1777, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32513653

RESUMO

OBJECTIVE: Management of acute severe UC (ASUC) during the novel COVID-19 pandemic presents significant dilemmas. We aimed to provide COVID-19-specific guidance using current British Society of Gastroenterology (BSG) guidelines as a reference point. DESIGN: We convened a RAND appropriateness panel comprising 14 gastroenterologists and an IBD nurse consultant supplemented by surgical and COVID-19 experts. Panellists rated the appropriateness of interventions for ASUC in the context of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Median scores and disagreement index (DI) were calculated. Results were discussed at a moderated meeting prior to a second survey. RESULTS: Panellists recommended that patients with ASUC should be isolated throughout their hospital stay and should have a SARS-CoV-2 swab performed on admission. Patients with a positive swab should be discussed with COVID-19 specialists. As per BSG guidance, intravenous hydrocortisone was considered appropriate as initial management; only in patients with COVID-19 pneumonia was its use deemed uncertain. In patients requiring rescue therapy, infliximab with continuing steroids was recommended. Delaying colectomy because of COVID-19 was deemed inappropriate. Steroid tapering as per BSG guidance was deemed appropriate for all patients apart from those with COVID-19 pneumonia in whom a 4-6 week taper was preferred. Post-ASUC maintenance therapy was dependent on SARS-CoV-2 status but, in general, biologics were more likely to be deemed appropriate than azathioprine or tofacitinib. Panellists deemed prophylactic anticoagulation postdischarge to be appropriate in patients with a positive SARS-CoV-2 swab. CONCLUSION: We have suggested COVID-19-specific adaptations to the BSG ASUC guideline using a RAND panel.


Assuntos
Betacoronavirus , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/terapia , Infecções por Coronavirus/epidemiologia , Controle de Infecções/organização & administração , Pneumonia Viral/epidemiologia , Doença Aguda , Colite Ulcerativa/virologia , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/transmissão , Gastroenterologia , Humanos , Pandemias/prevenção & controle , Seleção de Pacientes , Pneumonia Viral/prevenção & controle , Pneumonia Viral/transmissão , Guias de Prática Clínica como Assunto , Sociedades Médicas , Reino Unido
15.
Inflamm Bowel Dis ; 26(12): 1819-1830, 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-32385487

RESUMO

BACKGROUND: Vitamin D deficiency has been implicated in the pathogenesis of inflammatory bowel disease. Emerging literature suggests that optimization of vitamin D levels may be associated with improvements in disease activity and quality of life. We conducted a meta-analysis exploring the effect of vitamin D on serum 25-hydroxyvitamin D (s-25[OH]D) levels, clinical improvement, and biomarkers. METHODS: MEDLINE, EMBASE, the Cochrane Library, and sources for grey literature were searched from inception until September 2019. The primary outcome was s-25(OH)D mean differences. Heterogeneity was assessed using the χ 2 test and the I2 statistic. Review Manager software v. 5.3 was used. RESULTS: Twelve randomized controlled trials (n = 611) and 4 observational studies (n = 359) were included in the meta-analysis. On average, in the randomized controlled trials, vitamin D supplementation increased s-25(OH)D levels by 15.50 ng/mL (95% confidence interval [CI], 11.08-19.92, P ≤ 0.00001, I2 = 90%) and in observational studies they increased by 18.39 ng/mL (95% CI, 8.91-27.88, P = 0.0001, I2 = 82%). Subgroup analyses between vitamin D and placebo groups revealed that vitamin D increased s-25(OH)D by 14.85 ng/mL (95% CI, 9.96-19.73, P ≤ 0.00001, I2 = 90%) and when high doses of vitamin D were compared with low doses, high doses increased s-25(OH)D by 18.27 ng/mL (95% CI, 5.44-31.10, P = 0.005, I2 = 90%). The Harvey Bradshaw Index improved by -1.47 points (95% CI, -2.47 to -0.47, P = 0.004, I2 = 0%) and the high-sensitivity C-reactive protein decreased by -1.58 mg/L (95% CI, -2.95 to -0.21, P = 0.02, I2 = 0%). CONCLUSIONS: Vitamin D supplementation in patients with IBD and vitamin D deficiency is effective at correcting vitamin D levels and is associated with improvement in clinical and biochemical disease activity scores.

17.
Gut ; 69(6): 984-990, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32303607

RESUMO

The COVID-19 pandemic is putting unprecedented pressures on healthcare systems globally. Early insights have been made possible by rapid sharing of data from China and Italy. In the UK, we have rapidly mobilised inflammatory bowel disease (IBD) centres in order that preparations can be made to protect our patients and the clinical services they rely on. This is a novel coronavirus; much is unknown as to how it will affect people with IBD. We also lack information about the impact of different immunosuppressive medications. To address this uncertainty, the British Society of Gastroenterology (BSG) COVID-19 IBD Working Group has used the best available data and expert opinion to generate a risk grid that groups patients into highest, moderate and lowest risk categories. This grid allows patients to be instructed to follow the UK government's advice for shielding, stringent and standard advice regarding social distancing, respectively. Further considerations are given to service provision, medical and surgical therapy, endoscopy, imaging and clinical trials.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Doenças Inflamatórias Intestinais , Pandemias , Pneumonia Viral , Antivirais/efeitos adversos , Antivirais/uso terapêutico , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/terapia , Infecções por Coronavirus/transmissão , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Doenças Inflamatórias Intestinais/terapia , Pneumonia Viral/complicações , Pneumonia Viral/terapia , Pneumonia Viral/transmissão , Medição de Risco , Reino Unido
18.
Artigo em Inglês | MEDLINE | ID: mdl-32180822

RESUMO

Inflammatory bowel diseases, comprising Crohn's disease (CD) and ulcerative colitis (UC), are chronic, relapsing and remitting immune-mediated inflammatory diseases affecting the gastrointestinal tract. Vedolizumab is the first licensed drug in a group of 'gut-selective' biological agents used to treat inflammatory bowel diseases. The GEMINI registrational trials established the efficacy of vedolizumab for the induction and maintenance of remission in both CD and UC, with the most favourable results in tumour necrosis factor (TNF)-antagonist-naive patients. In recent years, a wealth of 'real-world' data has emerged supporting positive clinical, endoscopic and histological outcomes in patients treated with vedolizumab (VDZ) as well as reassuring safety data. More recently, the results of the first head-to-head trials of VDZ and TNF antagonists have been reported, as well as the results of a number of studies exploring the role of therapeutic drug monitoring with VDZ. This review brings together data reported on VDZ to date, including from the GEMINI trials, real-world data and emerging studies regarding therapeutic drug monitoring and immunogenicity. The safety profile of VDZ is also reviewed. Evolving treatment paradigms are explored, including data regarding the role of VDZ in perianal CD, post-operative complications and recurrence, extraintestinal manifestations and pregnancy.

19.
Gastrointest Endosc ; 91(4): 733-745, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31786161

RESUMO

Endoscopic assessment is currently the criterion standard for the diagnosis and assessment of mucosal disease activity, prognosis and monitoring for dysplasia, and assessment of response to therapy. Wider appreciation of the potential disconnect between symptoms and objective measures of disease activity and evidence that uncontrolled inflammation may lead to progressive intestinal injury and irreversible bowel damage with adverse events has led to the concept of treating to target. Treating to target is defined as treating patients with high risk for disease progression early to prevent or limit intestinal injury or disability. Endoscopic remission (mucosal healing) has emerged as a key goal of therapy. Although there are no currently validated definitions of endoscopic mucosal remission, the use of endoscopic scoring systems add uniformity and objectivity and aid standardization with reporting of mucosal appearance, augmenting clinical decision making. A plethora of scoring systems exist to define activity, response, and remission in both Crohn's disease and ulcerative colitis. In this review, we discuss the most commonly used endoscopic scoring systems and proposed definitions of response and remission, and how they can be integrated into a treat-to-target approach to optimize patient outcomes.

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