R. Orlando

Efficacy and safety of endoscopic balloon dilation of symptomatic intestinal Crohn's disease strictures.

AIM To evaluate prospectively the clinical efficacy and safety of endoscopic hydrostatic balloon dilation in a consecutive cohort of symptomatic intestinal Crohns disease strictures. METHODS Between September 2003 and December 2008 we performed endoscopic balloon dilations in 37 Crohns disease patients with 39 intestinal symptomatic strictures (4 naïve and 35 postoperative). Dilations were performed using a Rigiflex through-the-scope balloon. Clinical success rate was claimed if a patient remained asymptomatic and did not require surgery or further endoscopic dilation, following technical success. Actuarial curves of clinical, endoscopic (redilation) and surgical recurrence were obtained by Kaplan-Meier method. Demographic and disease variables were related to the main outcomes. RESULTS After a mean follow-up of 26.3 months (range, 2-61 months), the long-term global benefit rate was 89% (33/37). The 1-2-3 years cumulative symptom-free rates were respectively: 76%, 55% and 46%. Four patients were operated upon. Technical success predicts a lower rate of surgery. There were no complications related to the endoscopic procedures. CONCLUSIONS Endoscopic balloon dilation of symptomatic Crohns disease strictures may achieve clinical benefit in many patients and is a valid alternative to surgery in the management of the disease. Dilation may be repeated in recurrent intestinal obstructions and appears safe without morbidity.

Clinical benefit of vedolizumab on articular manifestations in patients with active spondyloarthritis associated with inflammatory bowel disease

Vedolizumab (VDZ) is a new biological agent which was recently approved for the treatment of inflammatory bowel disease (IBD)1 following the good clinical responses reported by clinical trials for both Crohns disease2 and ulcerative colitis.3 However, the effects of VDZ on extraintestinal manifestations were not reported in these trials, and the ‘real life’ experience is still limited. On these premises, we read with interest the recent work by Varkas et al 4 reporting a series of five patients with IBD who were treated with VDZ and promptly developed new onset or exacerbation of spondyloarthritis (SpA), irrespective of the response to treatment on intestinal symptoms. Although the hypotheses proposed …

Tolerability profile of thiopurines in inflammatory bowel disease: a prospective experience

Abstract Objectives: The occurrence of thiopurine-related adverse events (AEs) may complicate the management of patients with inflammatory bowel disease (IBD). We aimed to evaluate the tolerability of thiopurines in a current IBD setting. Materials and methods: All consecutive patients who started a treatment with azathioprine (AZA) from January 2010 to March 2016 were entered in a prospectively maintained database, and the AEs which led to the permanent discontinuation of the drug were reported. Results: Two hundred and fifty three patients were included. Median total follow-up was 32 months (range: 0.2–75 months). At the end of the study, AZA was discontinued in 160 patients (63.2%). The main reason leading to drug withdrawal was the occurrence of AEs (109/160 patients [68.1%]; cumulative incidence among the entire cohort: 43.1%). Overall, the most frequent AEs leading to treatment withdrawal were nausea (31/253 patients, 12.3%) and subjective symptoms, i.e., poorly defined side effects such as fatigue, headache and muscle pain (20/253 patients, 7.9%). Among the 109 AZA-intolerant patients, a switch to 6-mercaptopurine (6-MP) was performed in 44 cases (40.4%). At the end of follow-up, 6-MP was discontinued in 35/44 patients (79.5%), mostly due to AEs (29/35 patients, 82.8%). Azathioprine-induced hepatic and pancreatic toxicity was associated with male gender (p = .01 and p = .03, respectively), and occurrence of nausea with Crohn’s disease (p = .04). Conclusions: Our real-life prospective cohort showed the higher cumulative incidence of thiopurine withdrawal due to AEs reported to date. Switching from AZA to 6-MP was often ineffective.

The real-world effectiveness of vedolizumab on intestinal and articular outcomes in inflammatory bowel diseases

BACKGROUND The effectiveness of vedolizumab in real-world practice is under evaluation, while its role in inflammatory bowel disease-associated spondyloarthritis is still unclear. AIMS To report real-world data about the effectiveness of vedolizumab on intestinal and articular symptoms after 10 and 22 weeks of treatment. METHODS Web-based data from the cohort of the Sicilian Network for Inflammatory Bowel Disease (SN-IBD) were extracted to perform a prospective multicentre observational study. RESULTS 163 patients (84 with Crohns disease and 79 with ulcerative colitis) were included. At week 10, a steroid-free remission was achieved in 71 patients (43.6%), while at week 22 a steroid-free remission was obtained in 40.8% of patients. A response on articular symptoms was reported after 10 weeks of treatment in 17 out of 43 (39.5%) patients with active spondyloarthritis at baseline, and in 10 out of 22 (45.4%) patients at week 22. The only factor associated with articular response was the coexistence of clinical benefit on intestinal symptoms (at week 10: OR 8.471, p = 0.05; at week 22: OR 5.600, p = 0.08). CONCLUSIONS Vedolizumab showed good effectiveness after 10 and 22 weeks of treatment. A subset of patients reported improvement also on articular symptoms, probably as a consequence of the concomitant control of gut inflammation.

P387 The addition of an immunosuppressant is an effective optimization strategy after loss of response to anti-TNF-alpha monotherapy in patients with inflammatory bowel disease: a two-year experience

Crohn’s disease (CD), and that 6-thioguanine nucleotide (TGN) levels ≥125 pmol/8×108 RBC positively influence IFX pharmacokinetics. We aim to assess clinical outcomes after induction and during maintenance in CD patients treated with IFX and a thiopurine with respect to TGN and IFX levels. Methods: CD patients commenced on IFX between 2010–15 with or without concomitant thiopurines were retrospectively identified. “Response” to induction (CRP <5mg/L and absence of activity on physician global assessment) or “non response” (lack of clinical improvement during induction or flare requiring CD therapy adjustment or surgery during first 6 months) were assessed at week 14. Maintenance outcomes were assessed in 6-month semesters and classed as “response”, “flare” or “failure” (IFX cessation due to active disease or intolerance). TGN and IFX trough levels were recorded during induction and maintenance. Results: Of 89 patients (49 male, mean age 35y, range 18–61), combination therapy (n=73) had a higher response than IFX monotherapy (n=16) on induction (78% vs 50%, p=0.02). Median TGN was similar between responders and non-responders (314 vs 254, p=0.12), with TGN ≥125 patients more likely to respond (76% vs 47%, p=0.018). On multivariable analysis, TGN ≥125 was associated with response (OR 5.7; 95% CI: 1.6–20.1; p=0.006). Mean time to IFX failure was 26 months for monotherapy vs 53 months for combination therapy (p=0.55); a significant difference was observed when re-stratified by TGN ≥125, p=0.043 (Fig. 1).

Mycophenolate mofetil is a valid option in patients with inflammatory bowel disease resistant to TNF-α inhibitors and conventional immunosuppressants

BACKGROUND Few studies investigated the role of mycophenolate mofetil in inflammatory bowel disease, and none of them had specifically focused on patients with previous multiple intolerances and/or nonresponses to conventional immunosuppressants and biologics. AIMS To evaluate clinical benefit and tolerability profile of mycophenolate mofetil in patients with inflammatory bowel disease and limited treatment options. METHODS All consecutive patients with previous multiple intolerances and/or nonresponses to immunosuppressants and biologics who started an off-label treatment with mycophenolate mofetil from January 2014 to February 2016 were entered in a prospectively maintained database. RESULTS Twenty-four patients were included. Four weeks after initiation of mycophenolate mofetil therapy, a steroid-free remission was achieved in 4 patients (16.7%), while a clinical response in 13 (54.1%). At the end of follow-up, 12 patients (50.0%) remained on mycophenolate mofetil. Six achieved and maintained steroid-free remission throughout the study period (25.0%), and a further 6 patients (25.0%) achieved a clinical response with complete discontinuation of steroids. Twelve patients (50.0%) were considered as treatment failure, and five of them underwent surgery. CONCLUSIONS This is the first experience reporting a clinical benefit and tolerability of mycophenolate mofetil in patients with inflammatory bowel disease and multiple previous failures to other immunosuppressants and/or biologics.

The Addition of an Immunosuppressant After Loss of Response to Anti-TNFα Monotherapy in Inflammatory Bowel Disease: A 2-Year Study

Background The addition of an immunosuppressant (IM) after loss of response to anti-TNFα monotherapy is an emerging strategy of therapeutic optimization in patients with inflammatory bowel disease (IBD). However, few clinical data have been reported to date. We aimed to evaluate the efficacy and safety of this selective combination therapy in patients with IBD. Methods All consecutive patients with loss of response to anti-TNFα monotherapy despite an intensive dose optimization who added an IM from October 2014 to October 2016 were entered into a prospective database. Results Among 630 patients treated with anti-TNFα agents during the study period, 46 (7.3%) added an IM. A total of 31 patients (67.4%) were treated with an intravenous anti-TNFα (infliximab, as originator or biosimilar), while 15 (32.6%) were treated with a subcutaneous anti-TNFα agent (10 adalimumab and 5 golimumab). The mean duration of follow-up was 12.8 ± 7.3 months. Twenty-one patients (45.7%) remained on combination therapy at the end of follow-up: 15 (32.6%) maintained a steroid-free remission, and 6 (13.0%) achieved a clinical response. In patients who experienced treatment success, the median value of C-reactive protein decreased from baseline to the end of follow-up (13.2 vs 3.0, P = 0.01; normal values <5 mg/L). Adverse events leading to treatment discontinuation were reported in 8 out of 46 patients (17.4%). Conclusions In the largest cohort on this argument reported to date, the addition of an IM was an effective and safe optimization strategy after loss of response to anti-TNFα monotherapy. Low doses of IM were sufficient to achieve a clinical response.