Eva Iglesias

Safety of Thiopurines and Anti-TNF-α Drugs During Pregnancy in Patients With Inflammatory Bowel Disease

OBJECTIVES:The safety of thiopurines and anti-tumor necrosis factor-α (TNF-α) drugs during pregnancy remains controversial, as the experience with these drugs in this situation is limited. Our aim is to assess the safety of thiopurines and anti-TNF-α drugs for the treatment of inflammatory bowel disease (IBD) during pregnancy.METHODS:Retrospective, multicenter study in IBD patients. Pregnancies were classified according to the therapeutic regimens during pregnancy or during the 3 months before the conception: non-exposed group, pregnancies exposed to thiopurines alone (group A), and pregnancies exposed to anti-TNF-α drugs (group B). An unfavorable Global Pregnancy Outcome (GPO) was considered if pregnancy developed with obstetric complications in the mother and in the newborn.RESULTS:A total of 187 pregnancies in the group A, 66 pregnancies in the group B, and 318 pregnancies in the non-exposed group were included. The rate of unfavorable GPO was different among the three groups (31.8% in non-exposed group, 21.9% in group A, and 34.8% in group B), being lower in pregnancies under thiopurines than among non-exposed (P=0.01). The rate of pregnancy complications was similar among the three groups (27.7% in non-exposed, 20.9% in group A, and 30.3% in group B). The rate of neonatal complications was different among the three groups (23.3% in non-exposed group, 13.9% in group A, and 21.2% in group B), being lower in pregnancies under thiopurines than among non-exposed (P=0.01). In the multivariate analysis, the treatment with thiopurines (odds ratio=0.6; 95% confidence interval=0.4–0.9, P=0.02) was the only predictor of favorable GPO, whereas maternal age >35 years at conception was the only predictor of unfavorable GPO. The treatment with anti-TNF-α drugs was not associated with an unfavorable GPO.CONCLUSION:The treatment with thiopurines and anti-TNF-α drugs does not seem to increase the risk of complications during pregnancy and does seem to be safe for the newborn.

Infliximab salvage therapy after failure of ciclosporin in corticosteroid-refractory ulcerative colitis: a multicentre study

Aliment Pharmacol Ther 2012; 35: 275–283

Epidemiological risk factors in microscopic colitis: a prospective case-control study.

Background:The cause of collagenous colitis (CC) and lymphocytic colitis (LC) is unknown and epidemiological risk factors for CC and LC are not well studied. The aim was to evaluate in a case–control study epidemiological risk factors for CC and LC. Methods:In all, 120 patients with CC, 70 with CL, and 128 controls were included. For all cases and controls information was prospectively recorded. A binary logistic regression analysis was performed separately for CC and LC. Results:Independent associations observed with the diagnosis of CC were: current smoking (odds ratio [OR], 2.4), history of polyarthritis (OR, 20.8), and consumption of lansoprazole (OR, 6.4), low-dose aspirin (OR, 3.8), beta-blockers (OR, 3.6), and angiotensin II receptor antagonists (OR 0.20). In the case of LC they were: current smoking (OR, 3.8), associated autoimmune diseases (OR, 8), and consumption of sertraline (OR, 17.5), omeprazole (OR 2.7), low-dose aspirin (OR, 4.7), and oral antidiabetic drugs (OR, 0.14). Conclusions:The consumption of drugs, current smoking, and associated autoimmune diseases were independently associated with the risk of microscopic colitis.

Impact of current smoking on the clinical course of microscopic colitis.

Background:Whether current smoking worsens the clinical course of microscopic colitis (MC) is unknown. The aim was to evaluate the impact of smoking on the clinical course of MC. Methods:One hundred and eighty-four patients (72% women; age, 62.4 ± 1.1 years) with MC (118 collagenous colitis (CC) and 66 lymphocytic colitis (LC) were evaluated (39 of them were current smokers). In all the patients, smoking habits and clinical data at presentation, response to therapy, and clinical relapses during follow-up were prospectively recorded. Risk factors for clinical relapse were studied in 160 patients after a mean follow-up of 28 ± 1 months. Cox regression analysis was used to adjust for confounding variables. Results:Age at diarrhea onset was 63.0 ± 1.4 years in nonsmokers and 50.4 ± 2.1 years in current smokers (P < 0.001). There was no significant influence of smoking habit on either clinical symptoms at diagnosis or clinical remission rate. Clinical relapse rate was 25.5% for CC and 29.6% for LC, with the mean relapse-free time 28.8 months (95% confidence interval, 26.3–31.4) for CC and 26.9 months (95% confidence interval, 26–30.3) for LC (P = 0.5). Multivariate analysis showed that age at diagnosis (<50 years versus others; adjusted hazard ratio, 2.8; 95% confidence interval, 1.3–6; P = 0.01) was associated with risk of relapse of CC but not LC. Current smoking was not an independent risk factor for either CC or LC relapse. Conclusions:Active smokers developed MC more than a decade before nonsmokers. Age at diagnosis, but not smoking, was an independent risk factor of relapse in patients with CC.

Usefulness of oral beclometasone dipropionate in the treatment of active ulcerative colitis in clinical practice: The RECLICU Study

BACKGROUND Beclometasone dipropionate (BDP) is a relatively new topically acting oral steroid to treat mild to moderately active ulcerative colitis (UC). We estimate that 20,000 patients have received oral BDP in Spain in the last two years. Our aim was to evaluate the efficacy and safety of oral BDP in clinical practice. METHODS Retrospective and multicenter study that included 434 patients with active UC treated with BDP. The partial Mayo Clinic score (pMS, 0-9) was used to measure disease activity. Remission was defined as post-treatment pMS of 0 or 1; response as a decrease in pMS of 3 points or 2 points and >30%, and failure as lack of remission or response. RESULTS BDP dose was 5 mg/day in 88% of patients and mean treatment duration was 6.2 weeks. BDP achieved remission in 44.4%, response in 22.3% and failed in 33.2% of patients. Mean pMS decreased from 4.9 ± 1.3 to 2.4 ± 2.3 (p<0.0001). Remission rate was higher in mild and moderate than in severe UC (p<0.043) and tended to be higher in left-sided and extensive UC than in proctitis (p<0.06). Failure was less frequent in patients treated for >4 weeks (p<0.02). Mild adverse events were reported in 7.6% of patients. CONCLUSION BDP induces response or remission in two thirds of active UC patients, with a good safety profile. Patients with mild to moderate, left-sided or extensive UC, receiving BDP for more than 4 weeks are most likely to benefit from this treatment.

Diagnostic Performance of the Simple Clinical Colitis Activity Index Self-Administered Online at Home by Patients With Ulcerative Colitis: CRONICA-UC Study

OBJECTIVES:New e-health technologies can improve patient–physician communication and contribute to optimal patient care. We compared the diagnostic performance of the Simple Clinical Colitis Activity Index (SCCAI) self-administered by patients with ulcerative colitis (UC) at home (through a website) with the in-clinic gastroenterologist-assessed SCCAI.METHODS:Patients were followed-up over 6 months. At months 3 and 6, patients completed the SCCAI online at home; within 48 h, gastroenterologists (blinded to patients’ scores) completed the in-clinic SCCAI (reference). SCCAI scores were dichotomized to remission or active disease, and SCCAI changes in disease activity from month 3 to 6 were classed as worsening, stability, or improvement.RESULTS:A total of 199 patients (median age: 38 years; 56% female) contributed with 340 pairs of questionnaires. Correlation of SCCAI scores by patients and physicians was good (Spearman’s ρ=0.79), with 85% agreement for remission or activity (95% CI: 80.8−88.6, κ=0.66). The negative predictive value for active disease was 94.5% (91.4−96.6); the positive predictive value was 68.0% (58.8−69.2). Agreement between patient and physician was higher in the 168 month 6 pairs than in the 172 month 3 pairs of questionnaires (89.3% (83.6−93.1) vs. 80.8% (74.2−86.0), P=0.027).CONCLUSIONS:In patients with UC, SCCAI self-administration via an online tool resulted in a high percentage of agreement with evaluation by gastroenterologists, with a remarkably high negative predictive value for disease activity. Remote monitoring of UC patients is possible and might reduce hospital visits.

Clinical Outcomes of Golimumab as First, Second or Third Anti-tnf Agent in Patients with Moderate-to-severe Ulcerative Colitis

Background: Golimumab efficacy data in ulcerative colitis (UC) are limited to anti–tumor necrosis factor &agr; (TNF)-naive patients. The aim of this study was to assess the short-term and long-term efficacy of golimumab used as first, second, or third anti-TNF in UC in a real-life clinical setting. Methods: This retrospective multicenter cohort study included patients with moderate-to-severe UC treated with golimumab. The primary efficacy endpoints were short-term partial Mayo score response, long-term golimumab failure-free survival, and colectomy-free survival. Results: In 142 patients with UC, golimumab was administered as first (40%), second (23%), or third anti-TNF (37%). Ninety-two patients (65%, 95% confidence interval 56.6–73) achieved short-term clinical response. Forty-five patients (32%, 95% confidence interval 23.7–39.7) achieved clinical remission. Response rates for golimumab were 75% as first anti-TNF, 70% as second anti-TNF (ns versus first anti-TNF), and 50% as third anti-TNF (P = 0.007 versus first anti-TNF). After 12 months median follow-up (interquartile range 6–18), 60 patients (42%, 95% confidence interval 34–51) had golimumab failure, and 15 patients (11%) needed colectomy. Thirty-one patients (22%) needed golimumab dose escalation, and 71% of these regained response after escalation. Starting maintenance with 100 mg golimumab doses and short-term nonresponse were independent predictors of golimumab failure. Conclusions: In this real-life cohort of patients with UC, golimumab therapy was effective for inducing and maintaining clinical response. Although anti-TNF–naive patients had better outcomes, golimumab was also effective in anti-TNF–experienced patients. Only the patients given golimumab after previous failure of 2 anti-TNF agents had significantly worse outcomes. Golimumab dose escalation was beneficial and safe.

Adalimumab vs Azathioprine in the Prevention of Postoperative Crohn’s Disease Recurrence. A GETECCU Randomised Trial

Background and Aims Postoperative recurrence of Crohns disease [POR-CD] is almost certain if no prophylaxis is administered. Evidence for optimal treatment is lacking. Our aim was to compare the efficacy of adalimumab [ADA] and azathioprine [AZA] in this setting. Methods We performed a phase 3, 52-week, multicentre, randomised, superiority study [APPRECIA], in which patients with ileocolonic resection were randomised either to ADA 160-80-40 mg subcutaneously [SC] or AZA 2.5 mg/kg/day, both associated with metronidazole. The primary endpoint was endoscopic recurrence at 1 year [Rutgeerts i2b, i3, i4], as evaluated by a blinded central reader. Results We recruited 91 patients [median age 35.0 years, disease duration 6.0 years, 23.8% smokers, 7.1% previous resections]. The study drugs were administered to 84 patients. Treatment was discontinued owing to adverse events in 11 patients [13.1%]. Discontinuation was significantly less frequent in the ADA [4.4%] than in the AZA group [23.2%] (dif.: 18.6% [95% CI 4.1-33.2], p = 0.011). According to the intention-to-treat analysis, therapy failed in 23/39 patients in the AZA group [59%] and 19/45 patients in the ADA group [42.2%] [p = 0.12]. In the per-protocol analysis [61 patients with centrally evaluable images], recurrence was recorded in 8/24 [33.3%] patients in the AZA and 11/37 [29.7%] in the ADA group [p = 0.76]. No statistically significant differences between the groups were found for recurrence in magnetic resonance images, biological markers of activity, surgical procedures, or hospital admissions. Conclusions ADA has not demonstrated a better efficacy than AZA [both associated with metronidazole] for prophylaxis of POR-CD in an unselected population, although tolerance to ADA is significantly better. ClinicalTrials.gov NCT01564823.

Outcomes of Medical and Surgical Therapy for Entero-urinary Fistulas in Crohn's Disease.

BACKGROUND AND AIMS The aims of this study were to evaluate the frequency of entero-urinary fistulas in a cohort of Crohns disease (CD) patients and to analyse the outcomes of medical and surgical therapy. METHODS This multicentre retrospective study included all CD patients with entero-urinary fistulas diagnosed by the presence of clinical symptoms and confirmed at surgery or by radiological or endoscopic techniques. We evaluated outcomes of medical and surgical therapy. We defined remission as absence of clinical symptoms with a radiological confirmation of fistula closure. Cox regression analysis was performed to evaluate factors predictive of achieving remission without need for surgery. RESULTS Of 6081 CD patients screened, 97 had entero-urinary fistulas (frequency 1.6%). Seventy-five percent of fistulas occurred in men. After a median follow-up of 91 months, 96% of patients were in sustained remission. Thirty-three patients (35%) received anti-tumour necrosis factor (TNF) therapy. Of these, 45% achieved sustained remission (median follow-up 35 months) without needing surgery. More than 80% of patients required surgery, which induced remission (median follow-up 101 months) in 99% of them. Only the use of anti-TNF agents was associated with an increased rate of remission without need for surgery (hazard ratio 0.23, 95% confidence interval 0.12-0.44; p < 0.001). CONCLUSION In this large cohort of CD patients, the frequency of entero-urinary fistulas was lower than previously described. More than 80% of patients required surgery, and in all but one of them surgery induced sustained remission. In a selected subgroup of patients, anti-TNF may induce long-term fistula remission and radiographic closure, making it possible to avoid surgery.

Serial Tuberculin Skin Tests Improve the Detection of Latent Tuberculosis Infection in Patients With Inflammatory Bowel Disease

Aim To assess the likelihood of detecting latent tuberculosis infection [LTBI] by the positive conversion of a serial tuberculin skin test [TST] at 1 year in inflammatory bowel disease [IBD] patients with negative baseline two-step TST. Methods In this multicentre prospective cohort study, we evaluated rate and predictors of conversion of TST at 1 year in patients with negative baseline TST. We also evaluated management of patients who had a positive TST at baseline or a conversion at 1 year. In all patients we assessed TB cases occurring during follow-up. Results Of the 192 IBD patients receiving anti-tumour necrosis factor [TNF] and 220 IBD controls not receiving anti-TNF, 35 [8.5%, 95% CI 5.7-11.3] had positive conversion (median TST induration 13 mm, interquartile range [IQR] 9-16). Ten anti-TNF cohort patients [5.2%, 95% CI 2.5-9.5] versus 25 controls [11.4%, 95% CI 7.5-16.3] had TST conversion [p = 0.029]. In multivariate analysis, conversion was associated with smoking habit (odds ratio [OR] 2.19, 95% CI 1.08-3.97; p = 0.028). Anti-TNF-treated patients had a lower conversion rate [OR 0.41, 95% CI 0.20-0.83; p = 0.013]. The likelihood of conversion correlates with fewer immunosuppressive therapies between baseline TST and TST at 1 year [p = 0.042]. One case of active TB [isoniazid-resistant strain] occurred in a patient with positive baseline TST receiving anti-TNF [0.05 events/100 patient-years]. Conclusions Serial TST at 1 year can detect LTBI in IBD patients receiving anti-TNF therapy with negative baseline TST. Serial TST seems to be advisable to reduce the risk of TB cases associated with inability to detect LTBI in pre-treatment screening.