Upadacitinib In Patients Research Articles

Upadacitinib in patients with difficult-to treat Crohn’s disease

Abstract Background Upadacitinib has been approved to treat adults with moderate-to-severe Crohn’s disease (CD). Only a few studies have evaluated the effectiveness and safety of the drug in clinical practice, with even fewer focusing on patients with difficult-to-treat CD. Therefore, this study assessed the effectiveness and safety of upadacitinib in CD patients for whom all other available therapies had failed. Methods Patients with moderate-to-severe CD who had received upadacitinib after exhausting other treatments were included. The primary endpoint was corticosteroid-free clinical remission. Secondary endpoints included clinical response, biochemical remission, transmural response, transmural healing, deep remission, and continuation of therapy. Results The study included 64 CD patients. After 12 weeks, 51.6% of patients achieved steroid-free clinical remission, and 71.8% showed a clinical response. Biochemical remission was observed in 36.2% of patients, and transmural healing in 28.8%. At 24 weeks, clinical remission was achieved in 78% of patients continuing therapy. Therapy was discontinued before the end of the induction period in 14 patients (21.9%) due to therapy failure or adverse events. Conclusions This study highlights the efficacy of upadacitinib in CD patients for whom multiple drugs have failed, providing real-world evidence supporting its use in patients with moderate-to-severe CD unresponsive to other therapies.

S1341 Proactive Patient Engagement to Optimize the VICTRIVA Trial Protocol for Dual Targeted Therapy With Vedolizumab and Upadacitinib in Patients With Crohn’s Disease

S1341 Proactive Patient Engagement to Optimize the VICTRIVA Trial Protocol for Dual Targeted Therapy With Vedolizumab and Upadacitinib in Patients With Crohn’s Disease

Response to Upadacitinib in Patients with Inflammatory Bowel Disease Previously Treated with Tofacitinib.

Upadacitinib is an oral selective Janus kinase (JAK) inhibitor approved in the United States for ulcerative colitis (UC) and Crohn's disease (CD). However, data regarding its use following prior treatment with the JAK inhibitor tofacitinib is sparse. As such, we aimed to evaluate the effectiveness of upadacitinib therapy following tofacitinib exposure. This is a multicenter retrospective study of patients with confirmed diagnosis of UC or CD who received upadacitinib after prior treatment with tofacitinib. The primary outcome of interest was patient-reported clinical improvement at first follow-up. Secondary outcome included discontinuation of corticosteroids, change in Mayo Endoscopic Score (MES) and change in inflammatory marker levels. A total of 31 patients met the inclusion criteria. Following upadacitinib initiation, 80.6% (25/31) of patients had clinical improvement, including 92.3% (24/26) of those with UC and 20% (1/5) of those with CD. Of the patients initially requiring systemic corticosteroid therapy, 80% (12/15) were able to discontinue corticosteroids. Individual mean change of fecal calprotectin was a decrease of 501.5mcg/g ± 608.6 (P value = 0.01) while C-reactive protein decreased on average by 14.8mg/L ± 25.3 (P value = 0.02) compared to when patients were on tofacitinib, with significant changes observed in the UC cohort. In patients with UC, individual MES after initiating upadacitinib decreased compared to prior to tofacitinib discontinuation (P value = 0.04). Our study demonstrates that upadacitinib therapy in patients with prior tofacitinib exposure is associated with clinical improvement and a decrease in objective markers of inflammation in patients with UC.

Budget impact of upadacitinib in patients with moderate to severe rheumatoid arthritis in Argentina.

To analyze the budget impact of upadacitinib (UPA) 15 mg + methotrexate (MTX) for the treatment of moderate-to-severe rheumatoid arthritis (RA) in patients with an inadequate response to conventional disease-modifying antirheumatic drugs (cDMARD-IR) from the perspective of social security and the private health sector in Argentina. A budget impact analysis model was developed for a hypothetical cohort of 100,000 adults with health insurance coverage who were diagnosed with RA over a 5-year time horizon. The model parameters were obtained through literature review and validated by local experts. The costs are expressed in 2024 US dollars (USD). The introduction of UPA 15 mg + MTX for the treatment of moderate-to-severe RA and cDMARD-IR resulted in minimal increase, with a five-year total cumulative incremental cost of USD 1,855 for social security and USD 1,812 for the private health sector, representing 2% of the total budget. The acquisition cost of UPA was the most influential variable in the sensitivity analysis. The introduction of UPA 15 mg + MTX for the treatment of moderate-to-severe RA and cDMARD-IR can provide an effective treatment option with a minimal increase in costs for the healthcare system in Argentina, which is especially important in developing countries where health system budgets are more limited. Providing evidence-based estimates is a valuable tool for informing healthcare policies and can help policymakers make informed decisions about the allocation of healthcare resources to improve patient outcomes while also managing costs.

Efficacy and safety of upadacitinib in patients with rheumatoid arthritis and inadequate response or intolerance to biological treatments: results through 5 years from the SELECT-BEYOND study

ObjectiveTo evaluate the efficacy and safety of upadacitinib over 5 years among patients with rheumatoid arthritis (RA) in a long-term extension (LTE) of the SELECT-BEYOND phase 3 trial.MethodsPatients refractory to...

Safety and Efficacy of Upadacitinib in Patients with Rheumatoid Arthritis Refractory to Biologic DMARDs: Results Through Week 216 from the SELECT-CHOICE Study.

Thesafety and efficacy of upadacitinib 15mg (UPA15) through week 216 was evaluated in patients with rheumatoid arthritis (RA) from the long-term extension (LTE) of the phase 3 SELECT-CHOICE study. Patients with RA refractory to biologic disease-modifying antirheumatic drugs (bDMARDs) were randomized to UPA15 or abatacept (ABA) for 24weeks. During the open-label LTE, patients on ABA switched to UPA15 at week 24, and those on UPA15 continued treatment. Thesafety and efficacy of continuous UPA15, and ABA to UPA15, are summarized through week 216. The LTE was comprised of 91.4% (n = 277/303) of patients that initially received UPA15, and 89.6% (n =277/309) that initially received ABA. Of patients on UPA15 in the LTE (n =547), 28.3% (n =155/547) discontinued the study drug by week 216. Relative to other adverse events of special interest, and largely consistent with previous findings at week 24, higher rates of serious infection, COVID-19, herpes zoster, and elevated creatine phosphokinase were reported, while rates of malignancy excluding nonmelanoma skin cancer (NMSC), NMSC, major adverse cardiovascular event (MACE), and venous thromboembolism (VTE) were low. Long-term safety data with UPA through week 216 aligned with previous observations and no new safety risks were identified, including in patients who switched from ABA to UPA15. Proportions of patients achieving 28-joint disease activity score based on C-reactive protein (DAS28[CRP]) < 2.6/ ≤ 3.2, clinical disease activity index (CDAI) and simple disease activity index (SDAI) low disease activity/remission, ≥ 20%/50%/70% improvement in theAmerican College of Rheumatology (ACR20/50/70) response criteria, and Boolean remission were maintained or improved with UPA15 through week 216. Improvements in theHealth Assessment Questionnaire-Disability Index (HAQ-DI), patient's assessment of pain, and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) were also maintained or improved with UPA15 through week 216. Across all efficacy endpoints, similar results were observed in patients who switched from ABA to UPA15 versus continuous UPA15. Patients with an inadequate response to ≥ 1 prior tumor necrosis factor (TNF) inhibitor (UPA15: n =263/303, 86.8%; ABA to UPA15: n =273/309, 88.3%) showed similar responses to the total population. The long-term safety profile of UPA was consistent with previous findings and the broader RA clinical program. Compared to the primary analyses at week 24, efficacy responses were maintained or further improved with UPA15 through week 216 in patients with RA. Trial registration, ClinicalTrials.gov identifier: NCT03086343.

Correction of peroxidation of lipids with upadacitinib, a Janus kinase 1 inhibitor, in patients with true eczema

Objective. To study the effect of upadacitinib (UPA), a Janus kinase inhibitor 1 kinase, on the status of peroxidation of lipids (POL) and the antioxidant system in patients with true eczema. Subjects and methods. The investigation involved 64 patiens (43 males and 21 females) with true eczema (the mean age was 58.5±3.4 years). The patients were randomized into 2 groups: 1) 33 patients who received basic drug therapy (BDT); 2) 31 patients who received the Janus kinase 1 inhibitor UPA 15 mg/day during 2 months. The components of the antioxidant system and the state of POL were determined by enzyme immunoassay. Results. After 2 months of therapy, Group 1 showed no statistically significant changes in the analyzed parameters from the baseline level (p&gt;0.05). In Group 2, the total oxidative capacity of blood reduced by 1.27 tines; the level of oxidized low-density lipoproteins decreased by 1.28 times; the total antioxidant activity of blood increased by 1.24 times; the level of superoxidase dismutase increased by 1.43 times (p &lt; 0.001 for all values). Conclusion. The combined use of BDT and the JAK1 inhibitor UPA in patients with true eczema contributed to a statistically significant decline in the oxidative capacity of blood and POL products along with the enhanced antioxidant activity of blood.

Practical Use of Upadacitinib in Patients with Severe Atopic Dermatitis in a Real-World Setting: A Systematic Review.

Upadacitinib is a selective Janus kinase inhibitor approved for the treatment of severe atopic dermatitis (AD). This systematic review aims to summarize the most recent data in terms of effectiveness and safety of upadacitinib in the treatment of severe AD in a real-world setting. The review included a comprehensive search of databases, including PubMed, Google Scholar and Web of Science, according to Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. The literature search initially identified 242 studies. Of these, 214 were excluded after reviewing their titles and abstracts. We then conducted a full-text review of 25 studies, of which 17 met our inclusion criteria and were therefore included in our systematic review. The analysis of real-world studies showed high effectiveness of upadacitinib, in terms of both clinical signs and subjective symptoms, in different patient populations, including those resistant to other treatments. No new significant safety concerns have emerged as compared to randomized clinical trials.

P535 Effectiveness of upadacitinib in patients with Ulcerative Colitis: a real-life, multicenter, Italian report

Abstract Background Upadacitinib (UPA) is an oral, selective JAK inhibitor, that has recently received approval in Italy for the treatment of Ulcerative colitis (UC). To our knowledge, only few data of real-life studies are available. The aim of our observational data collection is to report the first real-life experiences with UPA in UC in terms of effectiveness and safety. Methods These data come from four Italian IBD centers. Adult patients with a diagnosis of UC, who have been prescribed UPA for active disease, after failure of at least one anti-TNF therapy, were enrolled. After an induction period of 8 weeks with a 45 mg daily dosage, treatment efficacy were assessed using the partial Mayo score (pMS) and the fecal calprotectin levels (CP). Treatment-related adverse events were also recorded. Results Among 20 patients who started UPA, 12 have completed the induction and were therefore enrolled and evaluated before starting UPA and at the end of the 8 weeks induction period. 83% (10 patients) had previously failed two or more biological therapies, including tofacitinib (3 patients, 25%). 3 patients (25%) were tapering systemic corticosteroids and 3 patients (25%) were receiving topical steroids when they started UPA. In the pre-treatment evaluation, the mean pMs was 5,25 (SD 2,26) and the median CP was 1270 ug/g (411- 3152). At the end of induction (week 8), 10 patients (83%) achieved clinical remission and one patient showed clinical response with a decrease of 6 points of pMS. One patient underwent colectomy after 4 weeks of ineffective therapy. The mean pMS at week 8 was 0 (SD 0,92) (Fig. 1), with a median CP of 88 ug/g (5-4639). Reported adverse events, that however did not cause drug discontinuation, were one case of leukopenia and one case of acne. To the date of the last evaluation, all patients maintained the achieved results, with a mean follow-up period of 92 days. A further analysis excluding the physician global assessment from pMS has been performed, to obtain a sort of patient-reported outcome 2 (PRO-2): the results, in terms of percentage reduction of the scores, were in line with the presented data. Despite the limited number of patients who completed the induction (11), we observed statistical significance in the difference between pretreatment and post-induction values of all the measured variables (Tab. 1, Fig. 1). Conclusion With this first Italian report in a real-life setting, UPA showed promising effects in rapidly inducing clinical remission and in normalizing a sensitive marker of intestinal inflammation. Moreover, it seems to be well tolerated. Long-term real-life studies, including endoscopic and histologic evaluations, are needed to confirm efficacy and safety of UPA in maintaining stable remission in UC patients.

OP10 Efficacy and safety of upadacitinib in patients with moderately to severely active Crohn’s Disease: results from the U-ENDURE long-term extension

Abstract Background Upadacitinib (UPA) is an oral Janus kinase inhibitor approved for the treatment of moderately to severely active Crohn’s disease (CD).1 The U-ENDURE (NCT03345823) maintenance study and long-term extension (LTE) evaluate the long-term efficacy and safety of UPA maintenance therapy. Here, we report the results of the U-ENDURE LTE. Methods Patients (pts) completing the U-ENDURE 52-week (wk) maintenance study were eligible to participate in the LTE and continue their previously assigned treatment (placebo [PBO], UPA 15 mg [UPA15] once daily [QD], or UPA 30 mg [UPA30] QD; blinded until the last pt completed maintenance wk52). Clinical response, clinical remission, endoscopic response, endoscopic remission, as well as high-sensitivity C-reactive protein (hs-CRP) and faecal calprotectin (FCP) were evaluated as-observed up to wk48 of the LTE among pts (PBO [N = 89], UPA15 [N = 107], UPA30 [N = 173]); excluding pts who received open-label UPA30 rescue therapy. Safety was assessed in all pts (PBO [N = 223], UPA15 [N = 221], UPA30 [N = 229]) from wk0 of the maintenance study up to LTE wk204 (cut-off date: 01 Aug 2023). Results At LTE wk0, the SF/APS clinical remission rates were 73.0%, 78.3%, and 80.3% for PBO, UPA15, and UPA30, respectively (Figure 1A). Similar rates were reported at LTE wk0 for CDAI clinical remission (PBO 75.3%, UPA15 81.3%, UPA30 80.9%; Figure 1B) and clinical response (CR-100: PBO 79.5%, UPA15 84.9%, UPA30 84.4%). Rates of clinical remission were stable through wk48 of the LTE. Endoscopic response (PBO 32.9%, UPA15 59.6%, UPA30 66.5%) and remission rates (PBO 27.8%, UPA15 42.4%, UPA30 47.3%) at LTE wk0 were sustained through wk48 with UPA while decreased with PBO (Figure 1C-D). At LTE wk0, the mean [95% CI] change from induction BL in hs-CRP was 1.8 [–0.4, 4.1], –13.2 [–17.9, –8.6], and –12.8 [–16.8, –8.9] for PBO, UPA15, and UPA30, respectively; sustained through wk48. Similar results were observed with FCP (mean [95% CI] change from induction BL: PBO 126 [–103, 356], UPA15 –2946 [–4121, –1772], UPA30 –1871 [–2577, –1165]). Severe adverse events (AEs) and serious AEs were lower with UPA treatment compared with PBO (Table 1). The rates of most AEs of special interest were similar between UPA and PBO; however, numerically higher rates of herpes zoster, adjudicated gastrointestinal perforations, neutropenia, lymphopenia, creatine phosphokinase elevation, and hepatic disorders were reported in pts treated with UPA vs PBO (Table 1). Conclusion In pts completing wk48 of the LTE, sustained efficacy was observed in clinical and endoscopic endpoints with over 2 years of UPA treatment, while maintaining an overall positive safety profile in pts with CD. Reference: 1. Loftus EV Jr, et al. N Engl J Med. 2023;388:1966–80

Treatment of atopic dermatitis with upadacitinib: adcare single center experience.

The role of upadacitinib in the management of moderate to severe atopic dermatitis seems promising, but more data on its efficacy and safety are needed. This study endeavors to assess the practical impact and safety of upadacitinib in patients with moderate to severe atopic dermatitis. The study aims to evaluate the efficacy and safety of upadacitinib in the treatment of moderate to severe atopic dermatitis, focusing on analyzing patient responses to the treatment. In this study, adult patients diagnosed with moderate to severe atopic dermatitis received upadacitinib at daily doses of 15 mg or 30 mg, as prescribed by their attending physicians. The therapeutic efficacy of upadacitinib was meticulously assessed using established clinical metrics. Simultaneously, a comprehensive safety assessment was conducted through monthly monitoring, including the evaluation of potential effects of upadacitinib intake on hepatic function, lipid profile, and hematopoiesis using the pertinent laboratory tests. Sixteen participants were enrolled in the study. At 1month follow-up, there was a significant reduction in the mean Eczema Area and Severity Index (EASI) score to 18.8 points, which further increased to 24 points at the 4-month mark. Additionally, 9 participants (56%) demonstrated an EASI-50 response after 1 month of treatment, with this response increasing to 9 participants (90%) after 4 months. Furthermore, enhanced therapeutic responses were observed at 4 months, with 6 patients (38%) achieving an EASI-75 response at 1month and 8 patients (80%) achieving this milestone at the 4-month follow-up. This study highlights the potential of upadacitinib as an effective treatment option for moderate to severe atopic dermatitis. While it demonstrates improved symptom management, close monitoring for potential adverse events, particularly infections and the known risks of Janus kinase inhibitors, is essential. Further research is essential to determine the long-term safety and efficacy of upadacitinib.

Safety and Efficacy of Upadacitinib for Atopic Dermatitis in Japan: Analysis of the 3-Year Phase 3 Rising Up Study.

Upadacitinib is an oral Janus kinase inhibitor approved in multiple countries for moderate-to-severe atopic dermatitis (AD). Here we present long-term data for up to 3years of continuous upadacitinib treatment in Japanese patients with AD. Rising Up was a phase 3, randomized, multicenter study in Japan investigating the safety and efficacy of upadacitinib in patients with moderate-to-severe AD. Patients aged 12-75years (weight ≥ 40kg if < 18years) were randomized 1:1:1 to receive upadacitinib 15mg, upadacitinib 30mg, or placebo through week16 (all in combination with topical corticosteroids). At week16, patients who received placebo were rerandomized 1:1 to upadacitinib 15mg or 30mg; topical corticosteroids were optional per investigator discretion from weeks16-160. Safety was assessed by monitoring adverse events (AEs). Efficacy assessments included patients who achieved ≥ 75%/≥ 90% improvement from baseline in Eczema Area and Severity Index (EASI 75/90), clear/almost clear on the validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD 0/1), or a ≥ 4-point improvement from baseline in Worst Pruritus Numerical Rating Scale (WP-NRS). Of 272 patients enrolled, 230 completed the study. Through week160, the long-term incidence rate of overall AEs was numerically higher with upadacitinib 30mg than 15mg; rates of serious AEs, AEs considered possibly related to study drug, AEs leading to discontinuation, and AEs of special interest were generally low and similar between dose groups. EASI 75, EASI 90, vIGA-AD 0/1, and WP-NRS response rates were generally greater with upadacitinib 30mg than 15mg and maintained through week160 with either dose. For up to 3years of continuous treatment, upadacitinib was well tolerated in Japanese patients, with a similar safety profile to that of short-term studies and durable long-term response rates for skin clearance and itch improvement. ClinicalTrials.gov identifier, NCT03661138.

Comparison of Long-Term Effectiveness and Safety ofUpadacitinibfor Atopic Dermatitis Between Dupilumab-Exposed and Dupilumab-Naïve Patients.

Upadacitinib is an oral selective Janus kinase-1 inhibitor approved for the treatment of moderate-to-severe atopic dermatitis (AD) in patients [Formula: see text] 12 years of age. In real life, upadacitinib currently represents a valid therapeutic option for patients failing available systemic therapies, in particular patients who discontinued dupilumab because of lack of efficacy or occurrence of adverse events. The objectives of the present study were to compare the effectiveness and safety of upadacitinib in patients affected by AD who had previously failed dupilumab therapy versus biologic naïve patients. A retrospective, multi-centre, observational, real-life study was conducted in four Italian dermatological referral centres (Milan, Perugia, Naples and Vicenza). Baseline characteristics included age, sex, AD history and severity, prior treatments, comorbidities and concomitant therapies. AD severity was assessed at baseline and at week 4 (W4), W16, W24 and W52, using Eczema Area Severity Index (EASI), Dermatology Life Quality Index (DLQI) and Pruritus Numerical Rating Scale (P-NRS) scores. Full blood count, hepatic and renal function, lipid panel, and muscle enzymes [lactate dehydrogenase (LDH) and creatine phosphokinase (CPK)] were assessed at baseline and at each follow-up visit. A total of 113 patients (72 males, 63.7%; mean age: 37.22 ± 16.8 years) were included in the analysis, all patients were in treatment and underwent follow-up period until W16, whilst 91 (80.5%) and 75 (66.4%) patients were in treatment and in follow-up period until W24 and W52, respectively. Mean EASI score significantly changed from 24.30 ± 10.27 to 1.28 ± 4.34, 0.74 ± 2.31 and 0.25 ± 1.34 at W16, W24 and W52, respectively (p < 0.0001). Specifically, at W16 the percentage of patients achieving EASI-75, EASI-90 and EASI-100 was 85.21, 76.35 and 66.11%, respectively. At W24, EASI-75, EASI-90 and EASI-100 were reached by 88.54, 85.42, and 78.37% of patients, respectively. Finally, 90.1% of patients achieved EASI-75, 88.3% achieved EASI-90 and 83.0% achieved EASI-100 at W52. This study confirmed the clinical effectiveness of upadacitinib treatment in adult patients in a real-world setting with moderate-to-severe AD who had discontinued dupilumab due to poor effectiveness or adverse events and who were biologic naïve; therefore, previous treatments do not seem to affect the response to upadacitinib treatment.

EE481 Cost-Effectiveness Analysis of Upadacitinib in Patients with Moderately to Severely Active Ulcerative Colitis in Greece

EE481 Cost-Effectiveness Analysis of Upadacitinib in Patients with Moderately to Severely Active Ulcerative Colitis in Greece

S7 Efficacy of Upadacitinib in Patients With One or More Prior Surgical Procedures for Crohn’s Disease: A Post Hoc Analysis of U-EXCEL, U-EXCEED, and U-ENDURE Phase 3 Trials

S7 Efficacy of Upadacitinib in Patients With One or More Prior Surgical Procedures for Crohn’s Disease: A Post Hoc Analysis of U-EXCEL, U-EXCEED, and U-ENDURE Phase 3 Trials

EE264 Cost-Effectiveness Analysis of Upadacitinib in Patients with Active Non-Radiographic Axial Spondyloarthritis in Greece

EE264 Cost-Effectiveness Analysis of Upadacitinib in Patients with Active Non-Radiographic Axial Spondyloarthritis in Greece

Impact of Baseline Corticosteroid Use on the Efficacy and Safety of Upadacitinib in Patients with Ulcerative Colitis: A Post Hoc Analysis of the Phase 3 Clinical Trial Programme.

This post hoc analysis assessed the efficacy and safety of upadacitinib in patients with moderately to severely active ulcerative colitis stratified by corticosteroid use from the ulcerative colitis Phase 3 clinical trial programme. Patients were randomised [1:2] to 8 weeks' placebo or upadacitinib 45 mg once daily; Week 8 responders were re-randomised [1:1:1] to 52 weeks' placebo or upadacitinib 15 or 30 mg daily. Corticosteroid dose was kept stable during induction but tapered according to a protocol-defined schedule [or investigator discretion] during maintenance Weeks 0-8. Efficacy outcomes and exposure-adjusted, treatment-emergent adverse event [TEAE] rates were assessed for induction and maintenance stratified by corticosteroid use at induction baseline. Overall, 377/988 [38%] patients were receiving corticosteroids at induction baseline [placebo, n = 133; upadacitinib 45 mg, n = 244] and 252 [37%] of the 681 clinical responders who entered maintenance were on corticosteroids at induction baseline [n = 84 for each treatment]. Similar proportions of patients receiving upadacitinib achieved clinical remission per Adapted Mayo Score with and without baseline corticosteroids at Weeks 8 and 52. The total proportion of patients re-initiating corticosteroids was higher with placebo [24/84;29%] vs upadacitinib 15 mg [16/81; 20%)] and 30 mg [11/81; 14%]. During induction, patients receiving corticosteroids at baseline had higher rates of TEAEs, serious TEAEs, and serious infections vs those not receiving corticosteroids; however, TEAE rates were similar during maintenance after corticosteroid withdrawal. Upadacitinib is an effective steroid-sparing treatment in patients with moderately to severely active ulcerative colitis. Clinicaltrials.gov identifiers: NCT02819635; NCT03653026.

S1160 Corticosteroid-Sparing Effect of Upadacitinib in Patients With Moderately-to-Severely Active Crohn’s Disease

S1160 Corticosteroid-Sparing Effect of Upadacitinib in Patients With Moderately-to-Severely Active Crohn’s Disease

S909 Efficacy of Upadacitinib in Patients With Crohn’s Disease Activity Index-Based Eligibility Criteria: Post Hoc Analysis of U-EXCEL, U-EXCEED, and U-ENDURE Phase 3 Trials

S909 Efficacy of Upadacitinib in Patients With Crohn’s Disease Activity Index-Based Eligibility Criteria: Post Hoc Analysis of U-EXCEL, U-EXCEED, and U-ENDURE Phase 3 Trials

Efficacy and safety of upadacitinib in patients with ankylosing spondylitis refractory to biologic therapy: 1-year results from the open-label extension of a phase III study

BackgroundUpadacitinib, a Janus kinase inhibitor, has demonstrated efficacy and an acceptable safety profile in patients with ankylosing spondylitis (AS) in the phase III SELECT-AXIS programs. We report the 1-year efficacy and safety in patients with AS and an inadequate response to biologic disease-modifying antirheumatic drugs (bDMARD-IR) from the SELECT-AXIS 2 study.MethodsPatients ≥ 18 years with active AS who met the modified New York criteria for AS and were bDMARD-IR received double-blind upadacitinib 15 mg once daily (QD) or placebo for 14 weeks. Patients who completed 14 weeks could enter an open-label extension and receive upadacitinib 15 mg QD for up to 2 years. Efficacy endpoints included the percentage of patients achieving ≥ 40% improvement in Assessment of SpondyloArthritis international Society response (ASAS40), Ankylosing Spondylitis Disease Activity Score (ASDAS) low disease activity (LDA), and ASDAS inactive disease (ID); and change from baseline in total and nocturnal back pain, and Bath Ankylosing Spondylitis Functional Index (BASFI). Subgroup analyses (bDMARD lack of efficacy versus intolerance, and prior tumor necrosis factor inhibitor [TNFi] versus interleukin-17 inhibitor [IL-17i] exposure) were conducted. Binary and continuous efficacy endpoints were assessed using non-responder imputation with multiple imputation (NRI-MI) and as observed (AO) analyses; and mixed-effects model repeated measures (MMRM) and AO, respectively. Safety was assessed based on adverse events. Data through week 52 are reported.ResultsOf 420 randomized patients, 366 (continuous upadacitinib: n = 181; placebo to upadacitinib: n = 185) completed 52 weeks of treatment. At week 52, in the continuous upadacitinib and placebo to upadacitinib groups, ASAS40, ASDAS LDA, and ASDAS ID were achieved by 66% and 65%, 57% and 55%, and 26% and 25% (all NRI-MI); and change from baseline in total back pain, nocturnal back pain, and BASFI was -4.5 and -4.3, -4.6 and -4.4, and -3.6 and -3.5 (all MMRM), respectively. No new safety risks were identified. Subgroup analyses were consistent with the overall study population.ConclusionsUpadacitinib 15 mg QD demonstrated sustained improvement up to 52 weeks in bDMARD-IR patients with AS. Efficacy was generally similar in patients with lack of efficacy versus intolerance to bDMARDs and prior TNFi versus IL-17i exposure.Trial registrationNCT02049138.