Maintenance Of Steroid-free Remission Research Articles

P605 Eight-year efficacy and safety of azathioprine treatment in the maintenance of steroid-free remission in inflammatory bowel disease patients

Abstract Background Azathioprine (AZA) and thiopurine are widely used for induction and maintenance of remission in steroid-dependent patients with inflammatory bowel disease (IBD). The aim of this study has been to investigate its efficacy and safety in maintaining steroid-free remission in steroid-dependent IBD patients eight years after the institution of treatment. Methods Data from consecutive IBD outpatients referred in our Institution, between 1985–2017, were reviewed and all patients treated with AZA were included in this retrospective study. AZA was administered at the recommended dose of 2–2.5 mg/kg. Results Out of 2992 consecutive IBD outpatients visited in the index period, AZA was prescribed to 446 patients, 245 (54.9%) were affected by Crohn’s disease (CD) and 201 (45.1%) by ulcerative colitis (UC). One hundred and ninety-six patients with a follow-up < 96 months were excluded from the study. Two hundred and fifty patients were evaluated, 140 (56%) with CD and 110 (44%) with UC. One hundred and thirty-eight (55.2%) were male and 112 (44.8%) female (average age of 35.48 ± 14.26 SD years, range 14–74 years). Eight year after the institution of treatment, 123 (49.2%) patients still were in steroid-free remission (82 CD vs. 41 UC, 58.6% and 37.3%, respectively, p = 0.0009), 71 (28.4%) had a relapse requiring retreatment with steroids (29 CD vs. 42 UC, 20.7% and 38.2%, respectively, p = 0.0030), 56 (22.4%) discontinued the treatment due to side effects (29 CD vs. 27 UC, 20.7% and 24.5%, respectively). The loss of response from first to eighth year of follow-up was low, about 21%. Conclusion Eight years after the onset of treatment about 50% of patients did not require further steroid courses. After the first-year loss of response was low in seven subsequent years. In the present series, the maintenance of steroid-free remission was significantly higher in CD than in UC patients. The occurrence of side effects leading to the withdrawal of AZA treatment has been low.

P543 Seven-year efficacy and safety of azathioprine treatment in the maintenance of steroid-free remission in inflammatory bowel disease patients

P543 Seven-year efficacy and safety of azathioprine treatment in the maintenance of steroid-free remission in inflammatory bowel disease patients

Sa1679 - Nudt15 Variant can Predict the Development of Azathioprine Induced Leucopenia and Allow Optimal Dosing in Indian Patients with Inflammatory Bowel Disease (IBD)

Background Azathioprine (AZA) is a widely used cost-effective option for maintenance of steroid-free remission of IBD. Leucopenia is a common complication. Recent GWAS studies have identified a strong association between NUDT 15 C415T variant and thiopurine-induced leucopenia in Asia. We assessed the prevalence of NUDT variant and its association with leucopenia and dosing of AZA in an Indian IBD cohort. Methods Prospectively collected data from our IBD Clinic Registry was analysed. 729 consecutive patients treated with AZA were included. The incidence of side effects, initial and maximum dose tolerated and discontinuation time was noted. Blood sample (at-80C) of these patients were retrieved from the biorepository. Age and sex matched group of healthy volunteers served as the control group. DNA was isolated (Qiagen) (n=729 AZA;179 controls). Genotyping of NUDT15C415T(rs116855232;p.R139C) carried out employing Taq-man probes on Real-time PCR(Step one-Life tech). The association of presence of risk variant of NUDT15 with the development of leucopenia, other side effects and maximum tolerated dosage was evaluated. Results 711/729 patients were included in the analysis (18 inadequate DNA). (IDDF2018-ABS-0269 Table1) There was no significant differences in the frequency of C/C, C/T and T/T genotypes of NUDT15p.R139C between AZA group (82.28%, 15.75%–1.97%) and control group (88.27%,11.73%–0%). 79/711 patients developed leucopenia (26/585 C/C; 42/112C/T; 11/14 T/T). Development of leucopenia was significantly higher in C/T and T/T compared to C/C (OR 15.609; CI 9.198–26.490) (table 1). The sensitivity (67.08%) and specificity (88.45%) for predicting AZA-induced leucopenia. C/T group discontinued treatment significantly earlier than C/C genotype. There was no incidence of hepatitis/pancreatitis in C/T and T/T groups and no significant difference in the mean dose tolerated wild (C/C) vs risk variant (C/T,T/T) carriers(1.33 mg/kg vs 1.196 mg/kg;p=0.014). Conclusions NUDT15 risk genotype frequency is around 15% in Indian population and can predict the development of leucopenia. The results suggest thiopurines should be avoided in homozygous T/T and low dose for C/T heterozygous genotypes. This has important implications for clinical practice and is a step towards personalised management of IBD.

P362 Six-year efficacy and safety of azathioprine treatment in the maintenance of steroid-free remission in inflammatory bowel disease patients

P362 Six-year efficacy and safety of azathioprine treatment in the maintenance of steroid-free remission in inflammatory bowel disease patients

P.11.1: Azathioprine in the Maintenance of Steroid-Free Remission in Inflammatory Bowel Disease Patients: Efficacy and Safety in Five Years of Follow-Up

P.11.1: Azathioprine in the Maintenance of Steroid-Free Remission in Inflammatory Bowel Disease Patients: Efficacy and Safety in Five Years of Follow-Up

P530 Azathioprine in the maintenance of steroid-free remission in inflammatory bowel disease patients: efficacy and safety in five years of follow-up

P530 Azathioprine in the maintenance of steroid-free remission in inflammatory bowel disease patients: efficacy and safety in five years of follow-up

PHARMACOECONOMIC EVLUATION OF 5-ASA APPLICATION IN LIGHT AND MEDIUM GRAVE DISSEMINATED (RECURRING) ULCERATIVE COLITIS

Inflammatory bowel diseases are chronic relapsing immune-mediated diseases affecting the gastrointestinal tract. The goal of therapy of ulcerative colitis (one of the IBD variants) is the achievement and maintenance of steroid-free remission, prevention of UC complications, prevention of surgeries and the timely use of surgical treatment when the process progresses and lifethreatening complications develop. It Is predominantly diagnosed in young people and leads to a significant reduction of quality of life. The peculiarity of the UC is its chronic recurrent course. Work on the choice of the most rational schemes of therapy continues goes on. New data from clinical studies on the efficacy and safety of modern methods of pharmacotherapy in addition to data on pharmacoepidemiology and pharmacoeconomics should help the medical community to develop the most optimal treatment strategies based on clinical and socio-economic factors. The standard therapy in the first phase is 5-ASA preparations, such as sulfasalazine and mesalazine. Given the efficacy and safety of each of these preparations it is possible to predict the frequency of transition of patients to more difficult treatment options systemic corticosteroids and biological agents arising in connection with this the possible side effects and additional economic load on the healing process. The article presents economic assessment of the use of two alternative first-line drugs for therapy - mesalazine and sulfasalazine; it shows a possible burden on the budget and subsequent benefit when switching to the most optimal treatment option.

PTU-052 The Impact of Thiopurines on Risk of Intestinal Surgery in Elderly-Onset IBD: Abstract PTU-052 Table 1

Introduction Thiopurines (TP) have an established role in the maintenance of steroid-free remission in IBD. Their role in reducing the need for surgery in younger populations has been recently highlighed. 1 TPs are associated with an increased risk of lymphoma in the elderly but their role in reducing the risk of surgery in patients with elderly-onset IBD (EO-IBD) is not established. We therefore aimed to evaluate the impact of TPs on the risk of surgery in EO-IBD, using a nationally representative research database. Methods This was a retrospective descriptive study using data from the Clinical Practice Research Datalink (CPRD). Incident cases of IBD were isolated using previously validated Read codes. Patients were included if they had codes for ulcerative colitis (UC) or Crohn’s disease (CD), and their date of diagnosis was on/after their 60 th birthday. Information extracted included sex, age at diagnosis, smoking status, and prescription data for IBD medications. Finally, we obtained data on our main outcomes: colectomy in UC and first intestinal surgery in CD. A multivariate Cox proportional hazard model was generated to deduce the risk of surgery according to TP use. The model was adjusted for potential confounders including sex, smoking, 5 ASA use and early steroid use (corticosteroid within 3 months of diagnosis). In a subgroup of TP users, a second proportional hazard model was used to define the impact of duration of TP treatment on the risk of surgery. Results 2758 and 1349 were identified with EO-UC and EO-CD respectively, with a mean follow up of 4.9 years. Mean age at diagnosis was 71.8 years. Table 1 demonstrates the summary demographic and prescription data for both groups. TP use was associated with an increased risk of colectomy in EO-UC (HR 3.5, CI 2.28–5.35, p Conclusion TP use for longer than 12 months is associated with a reduced risk of colectomy in EO-UC but in contrast does not appear appear to impact on the risk of first intestinal surgery in EO-CD. This is an important observation since the risk of TP-associated lymphoma is substantially increased in this age group. Further work is needed to evaluate the role of TPs in EO-IBD. Reference 1 Chhaya V, et al . Impact of early thiopurines in 2770 children and young people diagnosed with IBD: a national population-based study. Aliment Pharmacol Ther . 2015 Oct; 42 (8). Disclosure of Interest C. Alexakis: None Declared, S. Saxena Grant/research support from: SS is funded by a National Institute for Health Research Career Development Fellowship (NIHR CDF-2011-04-048). The views expressed are not necessarily those of the NHS, NIHR, or Department of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript, V. Chhaya: None Declared, E. Cecil Grant/research support from: EC is funded by a National Institute for Health Research Career Development Fellowship (NIHR CDF-2011-04-048). The views expressed are not necessarily those of the NHS, NIHR, or Department of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript, R. Pollok: None Declared

P411. Four-year efficacy and safety of azathioprine treatment in the maintenance of steroid-free remission in inflammatory bowel disease patients

P411. Four-year efficacy and safety of azathioprine treatment in the maintenance of steroid-free remission in inflammatory bowel disease patients

Therapy: Maintenance of steroid-free remission in nephrotic syndrome.

Maintaining steroid-free remission in children with idiopathic nephrotic syndrome is an important goal of therapy. A new trial provides evidence that mycophenolate mofetil can be added to the list of effective steroid-sparing agents. The majority of participants relapsed, however, highlighting an unmet need for more effective treatment modalities.

Routine use of thiopurines in maintaining remission in pediatric Crohn's disease.

To evaluate the effectiveness of thiopurines in maintaining steroid-free remission in routine clinical practice. The multi-center Pediatric Inflammatory Bowel Disease Network (PIBDNet) cohort study prospectively collected data on thiopurine naïve patients initiating mercaptopurine (6MP) or azathioprine. Patients with a diagnosis of Crohn's disease (CD) were included in our study upon entering remission as determined by physician global assessment (PGA) within 365 d of initiation of thiopurines. The primary outcome of the study was maintenance of steroid-free remission (SFR) at each follow up visit. Patients were considered treatment failures if there had been a change in PGA from remission to mild, moderate or severe disease; disease relapse between visits; need for rescue therapy (biologic therapy, methotrexate, steroids); thiopurine discontinuation, hospitalization or surgical intervention. A secondary outcome defined treatment failure as a change from remission to moderate or severe (not mild) in addition to the previously defined criteria. Sixty-five of 182 patients in the PIBDNet registry met criteria for inclusion in this study. Forty-five of 65 (69%) of included patients achieved remission within 180 d of thiopurine initiation. For the primary outcome, 47% and 23% of patients remained in SFR at 6 and 12 mo. The mean thiopurine dose at initiation for the 65 included patients was 0.89 ± 0.31 mg/kg per day. Metabolite levels were obtained in 48% (31/65) of the included patients with a mean 6TG level of 258 pmole/8 × 10(8) RBC ± 147. For the secondary outcome, 65% and 42% of patients remained in SFR at 6 and 12 mo. Thiopurines were less effective in maintaining remission for pediatric CD in this "real world" cohort than has been previously described. Variation in thiopurine dosing and metabolite measurement was found among practitioners.

P335 Two-year efficacy and safety of azathioprine treatment in the maintenance of steroid-free remission in inflammatory bowel disease patients

P335 Two-year efficacy and safety of azathioprine treatment in the maintenance of steroid-free remission in inflammatory bowel disease patients