Tremaine, William J.

Linked ContentThis article is linked to Cotter et al and Fernández‐Bañares and Gisbert papers. To view these articles visit https://doi.org/10.1111/apt.14133 and https://doi.org/10.1111/apt.14220.

SummaryBackgroundMicroscopic colitis (MC) is a common cause of chronic diarrhoea. Various treatment options have been described, but there are limited data describing outcomes of corticosteroid‐sparing treatments.AimTo evaluate the outcomes of patients with active MC treated with immune modulators.MethodsAll patients seen at Mayo Clinic, Rochester between January 1, 1997 and November 30, 2016 with a histological diagnosis of MC were identified. Patients treated with an immune modulator of interest were selected and clinical outcomes recorded.ResultsSeventy‐three MC patients (50 collagenous colitis and 23 lymphocytic colitis) with a median disease duration of 24 months (range, 7‐60) were included. The indications for treatment were budesonide‐refractoriness in 66%, budesonide dependence in 29%, and budesonide intolerance in 5%. Median age was 51.8 years (range, 43.4‐63.1) and 61 (84%) were female. Thiopurines were used in 49 patients (67%) for a median of 4 months (range, 1.5‐15). Complete and partial response occurred in 43% and 22% respectively. Adverse effects resulting in therapy cessation occurred in 17 patients (35%). Twelve patients (16%) were treated with methotrexate for a median of 14 months (3‐18.8). Complete and partial response occurred in 58% and 17%, respectively. Anti‐TNF therapy was used in 10 patients (14%) for a median of 4 months (range, 2.3‐5.5). Complete response occurred in four patients and partial response in four patients.ConclusionsThe majority of patients with active MC responded to thiopurines, methotrexate, or anti‐TNF therapy. Larger controlled studies are required to confirm the efficacy and safety of these medications in MC.

Objective Microscopic colitis (MC) is a common cause of chronic diarrhoea, often with additional symptoms. No validated instruments exist to assess disease activity in MC, making it difficult to compare efficacy of treatments between clinical trials. We aimed to identify clinical features that independently predicted disease severity and create a Microscopic Colitis Disease Activity Index (MCDAI). Design Patients with MC were prospectively administered a survey assessing their GI symptoms and the IBD Questionnaire (IBDQ). A single investigator also scored a physician global assessment (PGA) of disease severity on a 10-point scale. Multiple linear regression identified which symptoms best predicted the PGA. These symptoms were then combined in a weighted formula to create the MCDAI. The relationship between MCDAI and the IBDQ was investigated. Results Of the 175 patients enrolled, 13 (7.4%) did not complete the survey. The remaining 162 had a median age of 66 years (range, 57–73) and 74% were female. Several clinical features were independently associated with PGA (number of unformed stools daily, presence of nocturnal stools, abdominal pain, weight loss, faecal urgency and faecal incontinence). These parameters were combined to create the MCDAI, which strongly predicted the PGA (R 2 =0.80). A 1-unit decrease in disease activity (ΔMCDAI) was associated with a 9-unit increase in quality of life (ΔIBDQ). Conclusions The MCDAI strongly predicted the PGA and correlated with a validated measure of quality of life. Several symptoms in addition to diarrhoea are associated with disease severity in MC.

SummaryBackgroundCertolizumab pegol (CZP) is Food and Drug Administration (FDA)‐approved to treat Crohn's disease (CD). However, the efficacy and safety of CZP outside clinical trials are not well established.AimTo report the efficacy, safety and predictors of response to CZP in CD patients treated during a 6‐year period since FDA‐approval at a tertiary care centre.MethodsAll CD patients who received CZP at our institution between 2008 and 2013 were evaluated through retrospective medical record‐based review of steroid‐free complete response (SCR), loss of response and safety.ResultsA total of 358 patients were included. One hundred twelve patients (31.3%) and 189 (52.8%) received CZP as their second and third biological agent, respectively. The probability of SCR at 26 week was 19.9% (95% CI, 15.9–24.5). The probability of survival free of loss of response at 2 year was 45.7% (95% CI, 32.5–59.5). A predictor of SCR was age at CD diagnosis of >40 years old (hazard ratio, HR relative to those <17, 4.69; 95% CI, 1.75–12.61). Negative predictors included present perianal fistula (HR, 0.39; 95% CI, 0.16–0.98) and prior primary nonresponse to adalimumab (ADA; HR relative to secondary loss of response, 0.18; 95% CI, 0.04–0.76). Twenty‐three patients (6.4%) experienced serious adverse events and 19 patients (5.3%) discontinued CZP due to adverse events.ConclusionsCertolizumab pegol was both effective and well tolerated for the treatment of Crohn's disease in this large tertiary care centre enriched with biologics‐exposed patients. It may be more effective in patients without early‐aged Crohn's disease diagnosis, prior primary nonresponse to adalimumab and present perianal fistula.

SummaryBackgroundAnti‐TNFα biologics induce and maintain remission in inflammatory bowel disease (IBD). Also, they have been reported to induce or unmask idiopathic inflammatory demyelinating disease of the central nervous system (IIDD).AimTo determine if anti‐TNFα biologics increased the risk of IIDD in a large cohort of patients with IBD.MethodsWe retrospectively identified adult patients referred to the Mayo Clinic, Rochester, MN for management of IBD from a five state capture area (Minnesota, Wisconsin, North Dakota, South Dakota and Iowa) between 1996 and 2010. IIDDs were identified in both Crohn's disease (CD) and ulcerative colitis (UC) patients with and without anti‐TNFα exposure using the 2010 McDonald MRI criteria. The risk of IIDDs in patients with and without anti‐TNFα exposure was estimated for IBD; CD and UC groups separately.ResultsA total of 9095 patients with IBD were identified (4342 CD and 4753 UC). Four patients with CD with exposure to anti‐TNFα agents (4/2054) and five patients with CD without anti‐TNFα exposure (5/2288) developed a confirmed IIDD. One patient with UC with exposure to anti‐TNFα agents (1/1371) and five patients with UC without anti‐TNFα agents developed a confirmed IIDD (5/3382). The per cent of IIDDs in patients with and without anti‐TNFα exposure was; IBD: 0.15% and 0.18% (RR = 0.83, 95% CI: 0.28–2.42; P = 0.729); CD: 0.19% and 0.22% (RR = 0.89, 95% CI: 0.24–3.31; P = 0.863); UC: 0.07% and 0.15% (RR = 0.49, 95% CI: 0.06–4.22; P = 0.510).ConclusionAnti‐TNFα biologics do not appear to impact the risk of developing clinical idiopathic inflammatory demyelinating disease in patients with inflammatory bowel disease.

Objective: Although the epidemiology of microscopic colitis has been described in Europe, no such data exist from North America. We studied the incidence, prevalence and temporal trends of microscopic colitis in a geographically defined US population. Design and setting: In this population based cohort study, residents of Olmsted County, Minnesota, with a new diagnosis of microscopic colitis, and all who had colon biopsies for evaluation of diarrhoea, between 1 January 1985 and 31 December 2001 were identified. Biopsies were reviewed for confirmation (cases) and to identify missed cases (diarrhoea biopsies). Main outcome measures: Incidence rates, age and sex adjusted to the 2000 US white population. Poisson regression assessed the association of calendar period, age and sex with incidence. Results: We identified 130 incident cases for an overall rate of 8.6 cases per 100 000 person-years. There was a significant secular trend, with incidence increasing from 1.1 per 100 000 early in the study to 19.6 per 100 000 by the end (p<0.001). Rates increased with age (p<0.001). By subtype, the incidence was 3.1 per 100 000 for collagenous colitis and 5.5 per 100 000 for lymphocytic colitis. Collagenous colitis was associated with female sex (p<0.001) but lymphocytic colitis was not. Prevalence (per 100 000 persons) on 31 December 2001 was 103.0 (39.3 for collagenous colitis and 63.7 for lymphocytic colitis). Conclusions: The incidence of microscopic colitis has increased significantly over time, and by the end of the study, the incidence and prevalence were significantly higher than reported previously. Microscopic colitis is associated with older age, and collagenous colitis is associated with female sex.