Treatment Persistence Research Articles

OP37 Effect of the HLA-DQA1*05 allele on the efficacy of ustekinumab in patients with Crohn's Disease. Multicenter study based on the ENEIDA registry of GETECCU

Abstract Background HLA-DQA1*05 carriage is associated with the development of anti-drug antibodies and loss of response (LOR) to tumour necrosis factor antagonists (anti-TNF) in patients with inflammatory bowel diseases (IBD)1. Ustekinumab has shown very low rates of immunogenicity and presumably will not be affected by this risk. Identifying patients at high risk of treatment failure would be important when selecting therapy for IBD. The objective of this analysis was to investigate the relationship between the HLA- QA1*05 allele and ustekinumab on development of LOR and drug persistency. Methods This is a retrospective cohort study from a prospectively maintained ENEIDA registry. LOR was defined as recurrence or worsening of IBD related symptoms that required a change or intensification in treatment, hospitalization or surgery. Independent predictors of LOR were identified using univariate and multivariable Cox proportional hazard regression. The HLA-DQA1*05 allele was determined from a saliva sample (kit OGD-600 de DNA Genotek Oragene) and DNA extraction with the Maxwell® RSC-Stabilized Saliva DNA kits. Results 204 patients with Crohn's disease were included. Previous exposure to biological drugs was 96% (61% ≥2 biological drugs). Basal faecal calprotectin levels were 907±970μg/g and PCR levels 16.2±25 mg/dL. The median follow-up was 417±154 days. During this period, 25%, 16% and 13% of the patients required drug intensification, hospitalization or surgery, respectively. 43% of the patients included were carriers of one or two copies of the HLA-DQA1*05 allele. The presence/absence of this allele was not associated with LOR to ustekinumab (20% vs 16%, p = ns) nor with drug withdrawal (11% vs 6%, p = ns). In the multivariate analysis (COX regression), only the number of previous biological drugs was associated with ustekinumab persistency. Conclusion The presence of the HLA-DQA1*05 allele is not related to LOR or persistency of ustekinumab treatment. First-line treatment with ustekinumab rather than anti-TNF agents may be considered in HLA-DQA1*05-positive patients, particularly when the use of a concomitant immunosuppressant is contraindicated. 1. Sazonovs A, Kennedy NA, Moutsianas L, Heap GA, Rice DL, Reppell M, Bewshea CM, et al. PANTS Consortium. HLA-DQA1*05 Carriage Associated With Development of Anti-Drug Antibodies to Infliximab and Adalimumab in Patients With Crohn's Disease. Gastroenterology. 2020 Jan;158(1):189-199.

P1036 Persistence of biologics and advanced small molecules in 4th, 5th and 6th line of therapy for inflammatory bowel disease: a cross-sectional retrospective study

Abstract Background The choice of treatment for inflammatory bowel disease (IBD) with multiple prior drug failures, also known as difficult-to-treat (D2T) IBD, is an increasing challenge. We assessed the persistence of biologics and advanced small molecules, a surrogate for their efficacy, in patients with Crohn's disease (CD) and ulcerative colitis (UC) overall and in 4th, 5th and 6th lines of advanced treatment. Methods We retrospectively searched the electronic medical records of patients with IBD followed at the San Raffaele Hospital (Milan, Italy) up to 1 October 2023. Patients enrolled in clinical trials that changed disease management or receiving experimental drugs were excluded. Drug persistence was defined as the time from initiation to discontinuation of each treatment. Welch's ANOVA and Games-Howell's method for multiple comparisons were used. Results A total of 679 patients with moderate to severe IBD were included. 350 had CD, 326 UC, and 3 IBD-U. The mean disease duration was 11 years and 452 (66%) had received 5-aminosalicylates or antimetabolites as first maintenance treatment. Escalation to and changes between advanced treatments over time is summarised in Figure 1A. A greater use of anti-TNF agents was observed in the first lines of treatment whereas newer medications were proportionally more prescribed in refractory patients. In the overall analysis, regardless of the line of treatment, there was no difference in drug persistence between agents at 12 months (p=0.62), with approximately half of the patients having discontinued the drug. Figure 1B In subsequent lines of treatment, drug persistence decreased significantly in patients with CD (p=0.002). The trend was particularly pronounced from line 2, with a mean duration of 31 months, to line 7, with a mean duration of 11 months. In UC, the reduction was less evident and borderline non-significant (p=0.05), although it suggests a decrease in drug efficacy as the disease progresses. Figure 2 A, B In patients with D2T IBD, drug persistence in 4th, 5th and 6th line advanced treatment was similar for all agents (all p>0.05), indicating no clear advantage of one drug over the others. Figure 2 C, D, E Conclusion In CD, and possibly in UC, the persistence of patients on any advanced drug decreases with subsequent lines of treatment. None of the advanced agents showed a longer persistence time when used as a 4th, 5th or 6th line of treatment.

P046 Real-world data on the treatment with Mirikizumab in a mostly biological-experienced Ulcerative colitis cohort

Abstract Background Mirikizumab was approved for treating Ulcerative colitis (UC) in May 2023. However, real-world data, especially in biological-experienced patients, is scarce. We aimed to determine the treatment efficacy and persistence of Mirikizumab in mostly treatment-experienced UC patients. Methods All patients treated for UC in the Inflammatory Bowel Disease (IBD) outpatient clinic of the University Hospital Frankfurt from 07/23-11/23 were analyzed retrospectively. Data on clinical (Simple Clinical Colitis Activity Index (SCCAI)) and biochemical disease activity (fecal calprotectin (FC)), as well as patient history, were collected. Patients were followed up for at least 12 weeks. Results Seventeen patients with UC were included. Sixteen patients had already received at least one biological agent before starting Mirikizumab. Twelve patients were exposed to ≥ 2 biological agents, and four patients to ≥ 4 biological agents before starting Mirikizumab. One patient received Mirikizumab as a first-line treatment. 4 patients were treated with Ustekinumab before the therapy with Mirikizumab. Nine patients received oral steroids as a concomitant treatment. The median SCCAI at the time of the first infusion/start of induction was 7. We report a reduction in clinical disease activity from 7 to 5 based on the preliminary data of the SCCAI. Biochemical disease activity was assessed with FC levels. The median FC level at the start of the induction was 557.5. At week 8, the median FC level was 513 based on 7 out of 17 patients reached week eight until November 2023. Intravenous induction therapy was extended in 2 of 17 patients. There was no report of adverse events. Conclusion We report preliminary real-world data on the evidence and efficacy of Mirikizumab. In our interim analysis, Mirikizumab is an effective and safe treatment in biological-experienced UC patients.

P1088 Real-world data on the treatment with Upadacitinib in a biological-experienced Crohn's disease cohort

Abstract Background Upadacitinib was approved for the treatment of Crohn's disease in June 2023. However, real-world data, especially in biological-experienced patients, is scarce. We aimed to determine the treatment efficacy and persistence of Upadacitinib in treatment-experienced Crohn's disease (CD) patients Methods All patients treated for Crohn's disease in the IBD outpatient clinic of the University Hospital Frankfurt from 06/23-11/23 were retrospectively analyzed. Data on clinical (Harvey-Bradshaw index (HBI)) and biochemical disease activity (fecal calprotectin FC), as well as patient history, were collected. Patients were followed up for at least 12 weeks. Results Twenty patients with CD were included. All patients had already received at least one biological agent before starting upadacitinib. Six patients reported extraintestinal manifestations, most commonly arthralgia. Five patients had stenosis of the terminal/neoterminal ileum, and one patient underwent surgery during Upadacitinib induction. Five patients had preexisting fistulae; four reported fistulae activity at treatment initiation. The median Harvey-Bradshaw Index was 11. We report an HBI reduction after induction (8.5). The median FC level at induction was 719 ug/g. After the induction, the median FC was 216 ug/g. Nineteen of the twenty patients completed the induction period of 12 weeks at the time of this interim analysis. All patients continued with 30mg of Upadacitinib post-induction. The most common adverse event was acne. No significant changes in the patients' lipid status were observed. Conclusion We report preliminary real-world data on the treatment with upadacitinib. In our interim analysis, Upadacitinib is an effective and safe treatment in biological-experienced CD patients.

P468 Relevance of anti-drug antibodies in context of supra-therapeutic anti-TNF concentrations

Abstract Background The low serum concentration of anti-tumor necrosis factor-alpha (anti-TNFα) agents and the presence of anti-drug antibodies are related to poor therapeutic outcomes in inflammatory bowel disease (IBD). We aimed to evaluate the prognosis of patients having both antidrug antibodies and supratherapeutic drug concentrations. Methods IBD patients on maintenance infliximab (IFX) or adalimumab (ADA) therapy were prospectively recruited. Serum drug concentrations and antidrug antibodies were measured (Anser, Prometheus). The drug concentrations were classified as subtherapeutic (IFX: <3 µg/mL; ADA: <5 µg/mL), therapeutic (IFX: 3-8 µg/mL; ADA 5-10 µg/mL), and supratherapeutic (IFX > 8 µg/mL; ADA > 10 µg/mL) concentrations regardless of the timing of blood sample collection. We analysed the relationship between i) drug concentrations and ii) the presence and absence of anti-drug antibodies with use of systemic corticosteroids and anti-TNF discontinuation. Results Of 172 patients (122 CD [70.9%], 44 UC [25.6%], 3 IBD-U [1.7%], and 3 IBD-pouch [1.7%]), the median age was 32.3 years (range, 24.8-42.5), and the median duration of IBD was 9.7 years (range 5.3-15.6). IFX and ADA were used in 81 (47.1%) and 91 (52.9%) patients, respectively, and concurrent usage of immunomodulators and systemic corticosteroids was observed in 39 (22.7%) and 23 (13.4%) patients, respectively. Supratherapeutic, therapeutic, and subtherapeutic concentrations were observed in 74 (43.0%), 32 (18.6%), and 66 (38.4%), respectively. The patients with antidrug antibodies (n = 79, 45.9%) showed a higher frequency of having subtherapeutic drug concentrations (68.4% vs 12.9%, P < 0.001) compared to those without antibodies, and the presence of antibodies was an independent predictor of discontinuation of anti-TNFα agents (hazard ratio 3.50, 95% confidence interval 1.88-6.51, P < 0.001, Fig. 1A). In subgroup analysis, patients with antidrug antibodies and supratherapeutic drug concentration exhibited a tendency to have improved drug persistence compared to those with subtherapeutic drug concentration, albeit insignificantly (P = 0.099, Fig. 1B). However, the persistence in this group was still poorer than that observed in patients without antibodies (P = 0.003). Finally, neither anti-TNFα concentrations nor the presence of antidrug antibodies were associated with the need for additional systemic corticosteroid use within 6 months. Conclusion The presence of antidrug antibodies can predict the discontinuation of anti-TNFα agents despite supratherapeutic drug levels. While supratherapeutic drug concentration may improve the treatment persistence of anti-TNFα agents in patients with anti-drug antibodies, it does not last as long as in those without antibodies.

P569 Persistence and safety of upadacitinib in Crohn’s disease and ulcerative colitis in real life: results from a Spanish nationwide study

Abstract Background Upadacitinib (UPA) has demonstrated its efficacy in patients with inflammatory bowel disease (IBD) in clinical trials. However, these results may differ from those achieved in clinical practice. Thus, persistence and safety should be analysed in a real-world scenario. Main aim: to evaluate the persistence of UPA in real life, both in Crohn’s disease (CD) and ulcerative colitis (UC). Secondary aims: to assess the effectiveness and safety of UPA. Methods Multicentre, retrospective study of IBD patients who received UPA for IBD in clinical practice. Persistence was calculated from the date of the first dose to the date of the last dose of UPA. For effectiveness assessment, only patients with active IBD at baseline were considered. Active disease was defined as Harvey-Bradshaw index >4 in CD, and partial Mayo score >2 in UC. Negative imputation method was used to deal with missing data. Cox regression and logistic regression analyses were used to identify predictive factors of treatment persistence and effectiveness, respectively. Results One hundred patients from 34 centres were included, 68 with CD and 32 with UC. All patients had been previously exposed to biologics (median 4, IQR 3-4), and 26% to JAK inhibitors (78% in UC); 37% of them were on steroids at baseline. Regarding UPA survival, 81% of patients remained on UPA at month 6, and 66% at month 12 (figure 1). Loss of response was observed in 34% per patient-year of follow-up. Dose intensification was required in 18%, 72% of whom responded clinically. Finally, 23 patients interrupted UPA during the follow-up. Age below 40 at UPA start and CD were associated with higher risk of UPA withdrawal (HR 2.4; 95%CI:1.0-5.7 and HR 3.7; 95%CI:1.0-12.9, respectively). Seventy-eight patients had active disease at baseline and were considered for the effectiveness analysis. Short-term clinical remission was achieved in 51%, 59% and 64% at week 4, 8 and 12; focusing on the type of IBD, clinical remission was achieved in 79% of UC vs. 54% of CD (p=0.03) at week 12. In the long-term, 53% and 42% remained in clinical remission at months 6 and 12. Clinical remission in patients exposed to JAK inhibitors was achieved in 75% and 79% at week 8 and 12, respectively; and in the long-term, in 54% and 55% at months 6 and 12. A total of 41 patients (41%) presented at least one adverse event (Table 1). Conclusion In the largest real-life cohort of IBD patients treated with UPA, the proportion of patients maintaining UPA at 12 months seems relatively high, regardless of prior exposure to JAK inhibitors. UPA seems to be effective in inducing and maintaining clinical remission, both in CD and in UC. The safety profile was similar to that previously described.

P805 The persistence of subcutaneous infliximab is equivalent to intravenous form in patients with inflammatory bowel diseases

Abstract Background Switching from intravenous (IV) infliximab to subcutaneous (SC) is a new tool in treating patients with inflammatory bowel disease (IBD). This study aimed to evaluate the persistence and tolerance of SC IFX compared to IV IFX and to study outcomes of patients switched back to IV in a real-life patient cohort. Methods We conducted a retrospective monocentric study involving consecutive patients with IBD treated with maintenance IV IFX. The switch to SC was offered to patients in clinical remission receiving an IFX IV dose ≤ 10mg/kg every ≥ 6 weeks, and with a favorable patient profile (good adherence to IFX IV treatment, no decompensated psychiatric condition). Two groups were compared: a "switched" group receiving SC and a control group remaining on IV IFX due to an unfavorable patient profile or refusal of the switch. Results Among 360 consecutive patients treated by IV IFX, 282 were switched to SC and 78 remained on IV (44 due to refusal and 34 with an unfavorable profile). Both groups were similar in age, sex, and disease type and location; IV IFX dosage and frequency were higher in the IV group. With a median follow-up of 59 (46-67) weeks, SC IFX was discontinued in 28/282 (10%) patients (10 due to relapse, 10 by patient decision, and 8 due to intolerance), whereas it was stopped in 1/78 (1%) IV IFX patient for intolerance (p=0.01). Among the 28 who discontinued SC IFX, 27 reverted to IV, with 4 (1% of the switch group) permanently stopping IFX. Overall, persistence rates for IFX, irrespective of administration route, were comparable between the two groups at 52 weeks: 99% (96-100%) for IV versus 99% (98-100%) for SC (p=0.60). Adverse events were more frequent in the switched group than the control group (10% versus 3%, p=0.03). Primarily, this involved psoriasiform lesions in 9 patients; 4 patients reported an injection site reaction. The proportion of side effects leading to IFX discontinuation or hospitalization was identical in both groups (1 patient, 2%). Conclusion In a real-life cohort, switching from IV to SC IFX does not alter treatment persistence. In cases of poor tolerance to SC IFX, IV IFX re-initiation is effective. Switching to SC IFX is a therapeutic option for patients in remission on IV IFX.

P1082 A comparative analysis of persistence of advanced therapies among patients with Inflammatory Bowel Disease in Taiwan

Abstract Background The prevalence of inflammatory bowel disease (IBD) has been rapidly increasing in Asia. Advanced therapies have significantly improved outcomes for moderate to severe cases of IBD. With the expanding availability of advanced therapies, the selection of the most suitable treatment option has become crucial. Among various factors, treatment persistence holds paramount importance. We present the first study in Asia that compares real-world persistence rates among advanced therapies in IBD patients in Taiwan. Methods In this retrospective cohort study, we enrolled patients with IBD who were treated with five advanced therapies: infliximab (IFX), adalimumab (ADA), vedolizumab (VDZ), ustekinumab (UST), and tofacitinib (TOF) at Linkou Chang Gung Memorial Hospital between October 2017 and April 2023. UST followed a standard maintenance dosing frequency of every 12 weeks, while TOF was permitted for use only as a second-line treatment option for UC in Taiwan. We compared baseline data and drug persistence rates within the first 52 weeks for the overall group, biologic-naïve patients, and biologic-experienced patients. Results A total of 432 IBD patients were included, with 173 (40%) having ulcerative colitis (UC) and 259 (60%) having Crohn's disease (CD). The majority of patients were male, with a mean age of 43.6 years and a mean BMI of 22.6. UST showed the highest rate of dose escalation (22%). Across all five drugs, the primary reason of discontinuation was secondary loss of response, with IFX having the highest discontinuation rate due to side effects (20%). Other baseline characteristics were presented in Table 1. Kaplan-Meier analysis revealed that all biologics exhibited a persistence rate of over 50% within the initial 52 weeks. UST demonstrated the highest 52-week persistence rates in overall (87.88%, p < 0.001, Figure 1a), biologic-naïve (96.55%, p = 0.002, Figure 1b) and biologic-experienced CD patients (80.56%, p=0.043, Figure 1c). Although no statistically significant differences were observed between advanced therapies in overall UC patients and other subgroup analyses (Figure 1d-1f). VDZ showed highest 52-week persistence in overall (69.05%, p=0.078, Figure 1d) and biologic-experienced (60.87%, p=0.751, Figure 1f) UC patients. UST had highest 52-week persistence in biologic-naïve UC patients (100%, p=0.329, Figure 1e). Conclusion In this pioneering real-world comparison of advanced therapies across one year in Asia, UST exhibited superior 52-week persistence rates in CD patients. However, the rate of dose escalation in UST was also the highest among these therapies. The study's limitations include its single-center nature and relatively small sample size.

P562 Safety and persistence oh the first JAK inhibitor Tofacitinib in patients with ulcerative colitis

Abstract Background A drug safety warning was published in 2021 about the risks associated with tofacitinib, which were found in the Oral-Surveillance study. The European Medicines Agency (EMA) and the Spanish Agency for Medicines and Medical Products (AEMPS) have recommended, due to this warning, some precautions in the prescriptions: It should not be used in patients older than 65 years of age, people who are current or past smokers, or individuals with cardiovascular or malignancy risk factors unless there are no suitable treatment alternatives. The aim fo this study was to assess the safety and treatment persistence of tofacitinib in clinical practice in three Spanish third-level hospitals. Methods Retrospective observational multicenter study of patients with Ulcerative Colitis (UC) treated with tofacitinib from January 2019 to October 2023. Sex, age, line of treatment, persistence, adverse events, discontinuations and risk factors associated with the warning were evaluated. Information was collected from the hospital’s information systems. Results A total of 56 patients, 53% women, mean age 55 (18-72) years old. Tofacitinib was the first line treatment in 2% of the patients after loss of response to the conventional treatment, second line for 57%, third line for 30% and fourth line for 11% after biological drugs (infliximab, adalimumab, vedolizumab and ustekinumab). 52% of patients needed maintenance with the higher doses (10mg dose) after induction due to the lack of response with the 5 mg dose, with an average of 52 weeks. The mean persistence was 18 months (1-56), with 19,6% discontinuations due to primary failure and secondary failure. It must be noted that one patient, who received tofacitinib for three years, underwent appendicular neoplasia and finally died due to liver metastases. There was not discontinuation due to other adverse events, which were: 3,6% herpes zoster, 46,4% increased total cholesterol level >200 mg/dl (compared with the initial measurement), of which 19% received statins.There were 27 (48%) patients with risk factors associated with the safety warning: 37% cardiovascular risk, 3,7% older than 65 years, 11,1% previous malignancy, 18,5% current or past smokers and 29,6% had several of these risks. Conclusion In this multicenter real-world treatment-refractory UC population cohort, tofacitinib was well tolerated in the long term, even in the patients with risk factors related to the warning.

P718 Observational real-world evidence on the efficacy and safety of Janus Kinase inhibitors (JAKi) in the treatment of moderate to severe Active Ulcerative Colitis (UC)

Abstract Background Janus kinase inhibitors (JAKi) are the first orally administered treatment for Ulcerative Colitis (UC). The JAK family comprises of four intracellular tyrosine kinases inhibitors (JAK1, JAK2, JAK3 and Tyrosine Kinase 2). Inhibition of the JAK kinases lead to dampening of the inflammatory cytokines which drive Inflammatory Bowel Disease (IBD). Tofacitinib was the first generation pan-JAKi. This was followed by second generation JAKi: Filgotinib and Upadacinib which preferentially inhibit JAK1. We report on the real-world evidence on the efficacy and safety of JAKi in the treatment of UC in a tertiary IBD treatment centre. Methods Patients attending the IBD clinic at weeks 8-12 of initiation of therapy were included. Baseline demographics, disease activity and previous therapies were recorded. Clinical response was measured using the SCCAI and biochemical response was measured using calprotectin and CRP. We defined clinical response as ≥3 points reduction from baseline SCCAI, and clinical remission as SCCAI Score of <2.5, and / or biochemical remission as a CRP of less than 5 mg/L and a calprotectin level of < 250 mg/g. We also assessed treatment persistence, and the reasons for treatment cessation. Results The UC populations are shown in Table 1. 52 patients were included and an additional 24 patients who discontinued therapy early on were assessed to review secondary outcomes. Table 1 summarises the comparative outcomes of the JAKi. 81% and 63% of patients achieved clinical and biochemical remission respectively. Overall, 31% discontinued treatment due to lack of efficacy or adverse events. 60% of patients reported adverse events (AEs), 25 % of patients discontinued treatment due to AEs and 84% of patients continued treatment despite reporting AEs. The most common AEs were hypercholesteremia and cold and flu like symptoms and the most common AEs related with treatment discontinuation were recurrent infection or persistent deranged liver functions contributed to patients’ history of primary sclerosing cholangitis. No Serious Adverse Events were reported. 60% of patients on tofacitinib developed side effects and persisted with therapy, which included hypercholesteremia (67%), shingles (11%), flu like symptom (11%) and hair loss (11%). 53% had side effects with Filgotinib; hypercholesteremia (25%), cold like symptoms (25%), chest infection (13%), shingles (13%), acne (13%). 68% developed side effects with Upadacitinib; reports of acne (20%), cold and flu (33%), shingles and mood swings (7%) and high cholesterol (67%). Conclusion In this real-world cohort of UC patients, JAKi was effective in inducing remission and had an acceptable safety profile. The observed safety profile was as expected compared to clinical data results.

P618 Comparison of vedolizumab and ustekinumab treatment persistence in anti-TNF experienced Crohn's Disease patients

Abstract Background After the approval of vedolizumab and ustekinumab for the treatment of IBD, discussions continue regarding the prioritization of which drug will be used as the first-line treatment. Despite numerous studies in various indications on this matter, there is still no definitive information. It is known that the success of treatments decreases after the use of Anti-TNF in the first step. In this study, we aimed to compare the drug persistence rates of vedolizumab and ustekinumab used as second-line treatments in Crohn's patients with prior experience with Anti-TNF. Methods A total of 171 Anti-TNF experienced Crohn's disease patients were included in this study. Age, gender and other demographical info were recorded from patients electronic medial charts. Drug persistence rates were calculated and compared by using Kaplan-Meier Analysis. Results Seventy eight patients who received vedolizumab and 93 patients who received ustekinumab were analyzed. In vedolizumab group, 60% of the patients were male where as in ustekinumab group, 57% of the patients were male. Mean age was 39.4 years in vedolizumab group and 41.2 years in ustekinumab group. All patients were anti-TNF experienced. In addition, 70% of the patients in ustekinumab group was vedolizumab experienced. Concomitant azathioprine use was 56% in vedolizumab group where as 34% in ustekinumab group. Drug persistence was significantly higher in ustekinumab group when compared to vedolizumab group (Figure 1). Interestingly, concomitant azathioprine use did not change drug persistence in ustekinumab group however it increased drug persistence in vedolizumab group. Conclusion In anti-TNF experienced Crohn's disease patients, ustekinumab treatment persists more longer than vedolizumab treatment. Ustekinumab persistence was independent from concomitant azathiprine use where as concomitant azathioprine use increases vedolizumab persistence.

P698 Effectiveness and Safety of Ustekinumab for Ulcerative Colitis: A Brazilian Multicentre Real-World Observational Study

Abstract Background Real-world data on the effectiveness and safety of ustekinumab (UST) in ulcerative colitis (UC) are lacking in Latin America. In this study, we aimed to describe the effectiveness and safety of UST in a real-world multicentre cohort of Brazilian patients with UC. Methods We conducted a multicentre retrospective observational cohort study, including patients with moderate to severe UC (Total Mayo score 6-12, with an endoscopic subscore of 2 or 3) who received UST. The co-primary endpoints were clinical remission, defined as a total Mayo score ≤2 at 1 year, with a combined rectal bleeding and stool frequency subscore of ≤1, and endoscopic remission (endoscopic Mayo subscore of zero) within one year from baseline. Secondary endpoints included clinical response between weeks 12-16, endoscopic response within one year of starting UST, steroid-free clinical remission at week 52, and biochemical remission at week 52. We also evaluated UST treatment persistence and safety. Results A total of 50 patients were included (female, n=36, 72.0%), with a median disease duration of 9.2 years (1-27). Most patients had extensive colitis (n=38, 76.0%), and 43 (86.0%) were steroid-dependent at baseline. Forty patients (80.0%) were previously exposed to biologics (anti-TNF drugs, n=31; vedolizumab [VDZ], n=27). The co-primary endpoints of clinical remission and endoscopic remission at 1 year were achieved by 50.0% and 36.0% of patients, respectively. Clinical response at weeks 12-16 was 56.0%, endoscopic response, steroid-free clinical remission, and biochemical remission at week 52 were 68.0%, 67.4%, and 50.0%, respectively. The UST treatment persistence rates at 24 months was 73.7%. During the follow-up, 10 patients (20.0%) were hospitalized, mostly due to disease progression, and three patients required colectomy. Nine patients (18.0%) discontinued the drug mainly due to a lack of effectiveness. Twenty-six adverse events (AEs) were reported, 15 of which were considered as serious AEs. Conclusion This is the first real-world experience study to report the effectiveness and safety of UST specifically in a Latin American population. In this real-world cohort of difficult-to-treat UC patients, UST was associated with improvements in clinical, biochemical, and endoscopic outcomes. The safety profile was favorable, consistent with the known profile of UST.

P809 VARIETY BEACH: Real-world treatment patterns for vedolizumab intravenous and subcutaneous maintenance dosing observed over 1 year in studies from Belgium, Austria and Switzerland

Abstract Background Vedolizumab (VDZ) is approved for moderate to severe ulcerative colitis (UC) and Crohn’s disease (CD) as intravenous (IV) or subcutaneous (SC) formulations. Real-world data on VDZ treatment patterns in patients (pts) with inflammatory bowel disease (IBD) comparing VDZ IV or SC maintenance are still scarce. Methods Three prospective, non-interventional, observational studies following an umbrella protocol enrolled pts in Belgium (NCT04959851), Austria (NCT04890262) and Switzerland (NCT04989907) from Aug 2021 to Jun 2022. Adults initiating VDZ IV induction per the product label or continuing VDZ IV maintenance with the option to switch to SC administration, were eligible. The primary endpoint was VDZ treatment persistence at 1 year. Administration route, dosing frequency, reasons for regimen change and safety endpoints were also assessed. Non- responder imputation was applied for pts discontinuing treatment, discontinuing the study or lost to follow-up. A descriptive analysis was performed. Results Of 377 pts enrolled, 373 (UC=218, CD=155) were included in this interim analysis. At enrolment, 287 (77%) (UC=159, CD=128) already received VDZ IV maintenance for median 2.8 (0–12.6) years and 86 (23%) (UC=59, CD=27) started VDZ induction (baseline pt characteristics summarized in Table 1). For pts enrolled on VDZ IV maintenance, 12 discontinued vedolizumab, 34 discontinued the study and 14 were lost to follow-up; resulting in a VDZ persistence rate at 1 year of 79% (227/287). Of pts in this cohort persistent on VDZ at 1 year (n=227; UC=124, CD=103), 39% (88/227) switched from VDZ IV maintenance to SC during the study. For pts initiating VDZ induction, 10 discontinued VDZ, 16 discontinued the study and 3 were lost to follow-up; resulting in a VDZ treatment persistence of 66% (57/86). Of pts from this cohort persistent on VDZ at 1 year (n=57; UC=43, CD=14), 56% (32/57) switched to VDZ SC during the study (Figure 1). Overall, the most common reasons for administration route changes were pt decision 98/161 (61%; UC=56%, CD=67%), end of induction (planned switch: 10%; UC=14%, CD=5%) and disease adequately controlled (6%; UC=7%, CD=3%). Adverse events (AEs) occurred in 48 pts (13%) (UC=20, CD=28) and serious AEs in 6 pts (2%) (UC=3: Budd-Chiari syndrome, death cause unknown, UC worsening; CD=3: bronchopneumonia, gastroenteritis, recurrent urinary tract infection). Conclusion Real-world data from prospective observational studies in Belgium, Austria and Switzerland reported high persistence of VDZ IV and SC maintenance treatment over 1 year. Decisions on route of administration change were most frequently driven by patients. Safety results were consistent with the known safety profile of VDZ.

P610 Ustekinumab demonstrates superior treatment persistence over anti-TNF in Crohn’s disease patients previously treated with vedolizumab

Abstract Background With the rise in biologic therapies to manage moderate to severe inflammatory bowel disease (IBD), determining the optimal treatment sequence has become crucial. This aids in the selection of the next biologic agent after prior exposure or unresponsiveness to a previous regimen. Vedolizumab (VDZ) is a gut-specific α4β7-integrin inhibitor recognized for its efficacy in treating moderate to severe IBD. Yet, only a few studies have assessed the comparative effectiveness of alternative biologics, such as ustekinumab (UST) and antitumor necrosis factor agents (anti-TNF), following VDZ exposure. Methods In our retrospective study conducted at Chang Gung Memorial Hospital at Linkou, a leading 3700-bed medical facility in Taiwan, we examined 110 IBD patients who underwent treatment with UST or anti-TNF agents (including adalimumab and infliximab) from May 2019 to September 2023. UST's standard maintenance dosing in Taiwan is every 12 weeks. We utilized Kaplan-Meier analysis and Cox proportional hazards models to evaluate the 52-week treatment retention of UST versus anti-TNF. Results Of the 110 participants, 40 were diagnosed with ulcerative colitis (UC), and 70 with Crohn’s disease. The demographics between the anti-TNF and UST groups regarding age, gender, and body mass index were comparable. The primary reason for vedolizumab discontinuation in both groups was secondary non-response (Table 1). UST exhibited a notably higher 52-week retention in overall IBD (HR: 5.36, 95% CI: 1.84-15.62, P = 0.002, Figure 1a) and in Crohn’s disease patients (HR: 10.75, 95% CI: 1.34-86, P = 0.025, Figure 1b) compared to anti-TNF. While UST also showed superior persistence at 52 weeks in UC patients, the difference was not statistically significant (HR: 2.25, 95% CI: 0.63-8, P = 0.211, Figure 1c). At the 52-week mark, 73.5% of the anti-TNF group and 81% of the UST group were not on steroids. Secondary non-response was the predominant cause for discontinuation of the current biologic. Notably, UST required more frequent dose adjustments than anti-TNF. The safety profile of both treatments was comparable. Conclusion UST showed superior treatment persistence, compared to anti-TNF in Crohn's disease patients who had previously been exposed to vedolizumab. However, UST required more frequent dosing adjustments compared to anti-TNF.

Patterns of publicly funded naltrexone use among patients diagnosed with alcohol use disorder in Ontario.

Naltrexone is recommended first-line to manage alcohol use disorder (AUD). With previous studies indicating poor retention on naltrexone, we determined duration of naltrexone use and assessed the association between prescription setting and time to discontinuation in Ontario. We conducted a retrospective population-based cohort study among Ontario public drug beneficiaries diagnosed with AUD who initiated publicly funded naltrexone from June 2018 to September 2019. The primary outcome was time to naltrexone discontinuation, with a secondary analysis assessing receipt of at least one prescription refill. We used Cox proportional hazards models and logistic regression to test the association between prescription setting and each medication persistence outcome. Among 2531 new naltrexone patients with AUD, the median duration of naltrexone use was 31days and 394 (15.6%) continued naltrexone for 6months or longer. There was no association between setting of initiation and duration of naltrexone use; however, those initiating naltrexone following an acute inpatient hospital stay were more likely to fill a second prescription (aOR 1.43, 95% CI 0.96-2.14), while those initiating after an ED visit were less likely to be dispensed a second prescription (aOR = 0.69, 95% CI 0.52-0.90) compared to those starting in a physician's office. Persistence on naltrexone to treat an AUD is low, regardless of the setting of initiation. Further research is needed to elucidate the barriers encountered by patients with AUD that lead to poor treatment persistence in order to develop interventions that facilitate patient-centered access to evidence-based treatment for AUD in the province.

Improved medication adherence in COPD patients using tiotropium or tiotropium olodaterol with the HealthPrize digital behavior change program

ABSTRACT Objective To assess the impact of the HealthPrize RespiPoints™ program on treatment adherence and persistence in adults with chronic obstructive pulmonary disease (COPD). Methods In this retrospective cohort study, program participants and nonparticipants receiving tiotropium bromide (TIO) or TIO and olodaterol between 1 January 2015–31 March 2020 were propensity score matched (PSM), from the linked database of the HealthPrize patient list and IQVIA PharMetrics® Plus. Treatment adherence, persistence, healthcare resource utilization, and costs were compared. Multivariable logistic regression models assessed the odds of adherence (≥80% proportion of days covered [PDC]), adjusted risk of discontinuation, and adjusted total healthcare costs. Results Program participants (n = 262) demonstrated a 44% greater adherence during followup than nonparticipants (n = 262) (mean [standard deviation] PDC: 0.72 [0.27] vs 0.50 [0.36], p < 0.0001). Participants had higher odds of adherence vs nonparticipants (adjusted odds ratio: 2.51; 95% confidence interval: 1.72–3.66, p < 0.0001) and a lower percentage of participants discontinued their index medication (19.85% vs 33.59%, p = 0.0004). Fewer participants were hospitalized during follow-up (13.74% vs 17.56%, p = 0.23); adjusted total medical costs were 24% lower (p = 0.08). Higher pharmacy costs partially offset lower healthcare costs. Conclusions Program participants showed improved COPD medication adherence and persistence compared to nonparticipants.

Treatment persistence and switching patterns of ABP 501 in European patients with inflammatory bowel disease.

Approval of the adalimumab (ADA) biosimilar ABP 501 for inflammatory bowel disease (IBD) indications was based on the principle of extrapolation, without indication-specific clinical trial data. To evaluate the real-world treatment patterns of ABP 501 in patients with IBD. Retrospective analysis of pharmacy claims data from Germany and France. Continuously insured adult IBD patients who initiated ABP 501 between October 2018 and March 2020 were included. Treatment persistence, adherence, and post-ABP 501 switching patterns were evaluated for two mutually exclusive groups: ADA-naïve patients (i.e. no baseline use of ADA products) and ADA-experienced patients (i.e. previously treated with ADA products). A total of 3362 German patients and 733 French patients were included, with 54.4% and 65.3% being ADA-naïve patients, respectively. Median persistence (95% CI) on ABP 501 was 10.9 months (9.8-11.6) in ADA-naïve patients and 14.2 months (12.7-15.2) in ADA-experienced patients in Germany; for the French cohort, ADA-naïve and -experienced patients had median persistence of 12.8 months (10.2-14.7) and 11.5 months (8.8-14.4), respectively. During the first 12 months of ABP 501 initiation, 53.7% of German patients and 51.0% of French patients were adherent to the therapy. About 20% of patients in both countries switched from ABP 501 to another targeted therapy. In the German cohort, ADA-naïve patients most frequently switched to non-tumor necrosis factor inhibitor biologics, but ADA-experienced patients most commonly switched to reference product (RP); in the French cohort, patients most often switched to RP regardless of prior exposure to ADA products. About 50% of patients persisted on and were adherent to ABP 501 therapy during the first 12 months after treatment initiation in two large European countries. Post-ABP 501, switching patterns varied between countries, indicating diversified treatment practices warranting further research on reason(s) for switching and potential overall treatment outcomes.

Comment on: [10 years of biologic use patterns in patients with inflammatory bowel disease: treatment persistence, switching and dose intensification - a nationwide population-based study

Comment on: [10 years of biologic use patterns in patients with inflammatory bowel disease: treatment persistence, switching and dose intensification - a nationwide population-based study

A Medical Claims Database Study of Factors Associated with Medication Adherence and Treatment Persistence in Patients Receiving PCSK9 Monoclonal Antibodies.

To investigate medication adherence and treatment persistence in patients receiving proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies (mAbs) in Japan. Using an anonymized claims database from January 2015 to December 2021, data on adult patients at high risk for atherosclerotic cardiovascular disease or with a history of coronary artery disease (CAD) who had at least 1 prescription for PCSK9-mAbs were retrieved. In total, 276 patients were analyzed. The cumulative treatment persistence rate after 1 year was 67.0%. A multivariate analysis revealed that better adherence to oral low-density lipoprotein cholesterol (LDL-C)-lowering therapy in the year before starting PCSK9-mAbs (adjusted odds ratio [OR] 2.16) and a history of CAD for secondary prevention (adjusted OR 2.44) were associated with better adherence to PCSK9-mAbs in the first year. Better adherence to oral LDL-C-lowering therapy in the year before starting PCSK9-mAbs (adjusted OR 2.32) and a history of CAD for secondary prevention (adjusted OR 3.03) were also associated with a lower rate of discontinuation of PCSK9-mAbs. Age, sex, comorbidity, number of tablets taken daily (all medications), and number of hospital or clinic visits in the year prior to starting PCSK9-mAbs did not affect the persistence rate or adherence to PCSK9-mAbs in the multivariate analyses. Better adherence to oral LDL-C-lowering therapy and secondary prevention were identified as factors associated with better medication adherence and treatment persistence in patients receiving PCSK9-mAbs within the first year.

Treatment Patterns and Persistence Among Patients Newly Diagnosed With Migraine in South Korea: A Retrospective Analysis of Health Claims Data.

Migraine is one of the most common chronic neurological diseases worldwide. Although diverse treatment regimens have been recommended, there is insufficient evidence for which treatment patterns to apply in routine clinical settings. We used nationwide claims data from South Korea for 2015-2021 to identify incident migraine patients with at least one prescription for migraine. Patients were categorized according to their initial treatment classes and followed up from the date of treatment initiation. Treatment regimens included prophylactic treatments (antidepressants, anticonvulsants, beta blockers, calcium-channel blockers, and renin-angiotensin-aldosterone system [RAAS] inhibitors) and acute treatments (acetaminophen, antiemetics, aspirin, ergotamine, nonsteroidal anti-inflammatory drugs [NSAIDs], opioids, and triptans). The treatment patterns of migraine were evaluated until the end of the study period, including the secular trends, prevalence, persistence, and changes in migraine treatment. Among the 761,350 included patients who received migraine treatment, the most frequently prescribed acute treatment was an NSAID (69.9%), followed by acetaminophen (50.0%). The most-prescribed prophylactic treatment was flunarizine (36.9%), followed by propranolol (24.4%). Among the patients, 54.8% received acute treatment, 13.5% received prophylactic treatment, and 31.6% received both treatment types. However, 65.7% of the patients discontinued their treatment within 3 months. The 3-month persistence rate was highest for triptans (25.2%) among the acute treatments and for RAAS inhibitors (62.0%) among the prophylactic treatments. While the prevalence rates of medication use were found to align with current migraine guidelines, frequent switching and rapid discontinuation of drugs were observed in routine clinical settings.