Upadacitinib Treatment Research Articles

An Analysis of the Effectiveness and Safety of Upadacitinib in the Treatment of Inflammatory Bowel Disease: A Multicenter Real-World Study

Background and Aims: Inflammatory bowel disease (IBD) requires effective treatment options. Upadacitinib, a Janus kinase 1 (JAK1) inhibitor, has shown effectiveness in trials for Crohn’s disease (CD) and ulcerative colitis (UC). This study evaluates its real-world effectiveness and safety. Methods: We conducted a multicenter retrospective cohort study in tertiary care centers, involving patients treated with upadacitinib from January 2023 to September 2024. The study included adult patients aged 18 years or older, diagnosed with UC or CD, who received at least 8 weeks of upadacitinib therapy. Treatment outcomes were evaluated using established clinical, endoscopic, imaging, histological, and laboratory parameters. Results: A total of 236 IBD patients received upadacitinib treatment. In 80 UC patients at 8 weeks, 64.0% achieved steroid-free remission, 57.6% clinical remission, and 81.8% response. Endoscopic remission was 35.8% (p = 0.039), with 63.3% response and 35.8% mucosal healing. Histological remission reached 29.2% (p = 0.009). For 156 CD patients at 12 weeks, 76.8% achieved steroid-free remission (p < 0.001), 77.8% clinical remission (p < 0.001), and 81.0% response. Mean CDAI decreased from 214.9 to 117.5 (p < 0.001). Endoscopic remission was 19.4%, with 48.9% response and 4.9% mucosal healing. Radiological remission was 9.1% with 85.7% response. Intestinal ultrasound showed 5.7% remission and 56.7% response. Conclusions: Upadacitinib demonstrates significant real-world effectiveness and safety in IBD, particularly in biologic-resistant cases, as evidenced by high rates of steroid-free remission and clinical response. These outcomes are likely due to its targeted JAK1 inhibition, which effectively reduces inflammation and promotes mucosal healing. Future research should focus on long-term safety, comparative effectiveness with other biologics, and its application in diverse patient populations. These findings support the integration of upadacitinib into IBD management strategies.

Repigmentation in non-segmental vitiligo using the Janus kinase inhibitor upadacitinib, a retrospective case series.

Vitiligo is the most frequently diagnosed depigmentation disease, affecting nearly 0.5-2% of individuals worldwide. This disorder is characterized by melanocyte loss, which results in skin and hair depigmentation. Psychological problems are common in patients, especially in those with the involvement of the face and hands. Several studies have recently focused on the use of JAK inhibitors for vitiligo treatment. However, studies on the selective JAK1 inhibitor upadacitinib for vitiligo treatment are limited. This study aimed to assess the efficacy and safety of upadacitinib in the treatment of vitiligo. This retrospective case series included five patients diagnosed with non-segmental vitiligo who were treated with upadacitinib for 4 months or longer. Disease severity was assessed using the Vitiligo Area Scoring Index (VASI). Five patients took 15mg of upadacitinib orally for 4 consecutive months, and all achieved repigmentation. The plasma collected from the peripheral blood of the four patients showed that the CXCL9 level dropped after upadacitinib treatment. However, the CXCL10 level did not change significantly using enzyme-linked immunosorbent assay (ELISA). Flow cytometry revealed that the ratio of CD4 + CD3+/CD8 + CD3 + T cells in the blood samples tended to decrease through the treatment. And the Th1-like Tregs (CD4 + Foxp3 + IFN-γ + Tregs) were also downregulated in the peripheral blood. In conclusion, the JAK1 inhibitor upadacitinib was found to be effective and safe for treating non-segmental vitiligo.

133 Interim analysis of upadacitinib treatment in the TREATgermany registry

133 Interim analysis of upadacitinib treatment in the TREATgermany registry

Real-World Effectiveness of Upadacitinib in Moderate‑to‑Severe Atopic Dermatitis (AD): Results From Longitudinal Analyses of the CorEvitas AD Registry

Introduction: Clinical trials demonstrated that upadacitinib is efficacious in treating atopic dermatitis (AD). Its real-world effectiveness is less understood. In this study, we investigated the longitudinal real-world outcomes of upadacitinib-treated adults in the CorEvitas AD Registry. Methods: The CorEvitas AD Registry is a prospective, non-interventional registry of adults diagnosed with AD in the United States and Canada. We evaluated participants enrolled through April 30, 2024 with data available prior to upadacitinib exposure (baseline) and at the six-month follow-up visit, and were receiving upadacitinib at the follow-up visit. Outcomes evaluated include the achievement of: Validated Investigators Global Assessment Scale for Atopic Dermatitis (vIGA-ADTM) of “clear” or “almost clear” among participants rated “mild” or worse at baseline (vIGA-AD 0/1); Eczema Area and Severity Index improvement of ≥75%/≥90%/100% from baseline (EASI 75/90/100); Peak Pruritus Numeric Rating Scale (PP-NRS) improvement ≥4 among participants with a score ≥4 at baseline (∆PP-NRS≥4); PP-NRS score of 0 or 1 among participants with a score >1 at baseline (PP-NRS 0/1); Dermatology Life Quality Index (DLQI) score improvement ≥4 among participants with a score ≥4 at baseline (∆DLQI≥4); and DLQI score of 0 or 1 among participants with a score >1 at baseline (DLQI 0/1). Simultaneous achievement of both EASI 90 & PP-NRS 0/1 was also assessed. Data were analyzed as observed with no imputation. Safety events were not assessed in this analysis. Results: The longitudinal analysis included 192 participants (mean age 46.2 years; 57.8% female; 69.8% White; 43.8% prior exposure to dupilumab or tralokinumab; 64.4% receiving 15 mg dose at follow-up visit; mean upadacitinib treatment duration of 6.0 months). More than half achieved clear/almost clear skin (66.1% vIGA-AD 0/1), EASI 75 (69.3%), and EASI 90 (59.2%); 45.3% achieved complete skin clearance (EASI 100). More than 40% reported little-to-no itch (44.4% PP-NRS 0/1) and no impact of AD on quality of life (43.3% DLQI 0/1), and more than half reported meaningful improvements in itch (58.6% ∆PP-NRS≥4) and quality of life (76.0% ∆DLQI≥4). Simultaneous attainment of both EASI 90 & PP-NRS 0/1 was achieved in 46.6% of participants at 6 months. Conclusions: In the real-world setting, the majority of adults treated and remained on upadacitinib achieved clinically meaningful outcomes in skin lesions, itch, and quality of life, with many achieving complete skin clearance, little-to-no itch, and experiencing no impact of AD on their quality of life. These findings underscore upadacitinib's potential to offer multidimensional relief to patients with AD in everyday clinical practice.

Long-Term Maintenance of Optimal Treatment Targets for Skin and Itch Outcomes With Upadacitinib in Moderate-to-Severe Atopic Dermatitis: 140-Week Results From the Phase 3 Measure Up 1 and 2 Studies

Introduction: Despite undergoing prolonged systemic therapy, many patients with moderate-to-severe atopic dermatitis (AD) do not achieve optimal targets for skin and itch outcomes as defined by Aiming High in Eczema/AD (AHEAD) recommendations (eg, ≥90% improvement from baseline in Eczema Area and Severity Index [EASI 90] and Worst Pruritus Numerical Rating Scale [WP-NRS] score of 0/1 [no/minimal itch]). We evaluated long-term maintenance of optimal treatment targets with upadacitinib, an oral selective JAK inhibitor approved for moderate-to-severe AD in adolescents and adults. Methods: This 140-week interim analysis included adolescents and adults with moderate-to-severe AD who were randomized at baseline to upadacitinib 15 mg (UPA15) or 30 mg (UPA30) in the ongoing, phase 3, double-blind Measure Up 1 and 2 studies. Assessments included the proportion of patients (at the population level) who maintained EASI 90, WP-NRS 0/1, or simultaneous achievement of EASI 90 + WP-NRS 0/1 responses from week 16 (end of the placebo-controlled period) onwards. Data are reported as observed cases with no imputation for missing data. Results: Among patients who achieved EASI 90 at week 16 (UPA15, n=298; UPA30, n=384), EASI 90 was maintained by 79.8% (UPA15) and 83.7% (UPA30) at week 52, 76.7% (UPA15) and 83.0% (UPA30) at week 100, and 74.0% (UPA15) and 84.2% (UPA30) at week 140. Of patients achieving WP-NRS 0/1 at week 16 (UPA15, n=193; UPA30, n=281), WP-NRS 0/1 was maintained by 69.4% (UPA15) and 72.0% (UPA30) at week 52, 65.6% (UPA15) and 68.4% (UPA30) at week 100, and 62.3% (UPA15) and 66.0% (UPA30) at week 140. Of patients simultaneously achieving EASI 90 + WP-NRS 0/1 at week 16 (UPA15, n=156; UPA30, n=243), maintenance was achieved by 68.1% (UPA15) and 70.8% (UPA30) at week 52, 62.7% (UPA15) and 66.5% (UPA30) at week 100, and 58.7% (UPA15) and 64.4% (UPA30) at week 140. Among patients who did not maintain optimal outcomes, most still achieved clinically meaningful responses. Conclusion: Most patients maintained optimal skin and itch outcomes through 140 weeks of upadacitinib treatment, demonstrating its potential to provide sustained long-term disease control in atopic dermatitis.

Successful treatment of refractory palmoplantar pustulosis by upadacitinib: report of 28 patients.

Upadacitinib, a specific JAK1 inhibitor, has minimal effect on other JAK subtypes. It influences the inflammatory process in various ways. Upadacitinib has been approved for conditions such as rheumatoid arthritis, psoriatic arthritis, atopic dermatitis, and ulcerative colitis in various countries. The purpose of this study is to assess the clinical efficacy and safety of upadacitinib in patients with refractory palmoplantar pustulosis who have not responded to conventional treatments (e.g., Acitretin, Tripterygium wilfordii Hook F, cyclosporine, methotrexate). We conducted a retrospective collection of clinical data from 28 patients who received upadacitinib treatment at the Department of Dermatology, First Affiliated Hospital of Suzhou University, from July 2022 to December 2023. We evaluated the Palmoplantar Pustulosis Area and Severity Index (PPPASI) scores, Dermatology Life Quality Index (DLQI) scores, and Physician's Global Assessment (PGA) scores before and after treatment. We also recorded any adverse events during the treatment process. A total of 28 patients were diagnosed with PPP, including 10 males and 18 females, and 8 patients (3 males and 5 females) were diagnosed with SAPHO syndrome. The mean age was (36.3 ± 10.5) years. After 12 weeks of treatment, PPPASI scores decreased from baseline (13.86 ± 2.76) to (5.56 ± 1.08), with a statistically significant difference (p < 0.05). DLQI scores decreased from (12.55 ± 4.56) to (2.03 ± 1.13), also showing a statistically significant difference (p < 0.05). Additionally, 20 patients achieved a PGA score of 0/1. No severe adverse events were reported during the treatment and follow-up period. Upadacitinib could be an additional safe and effective treatment for treating refractory palmoplantar pustulosis with a potential benefit on patients' quality of life. Further studies are needed to assess its short-and long-term efficacy and safety in larger sample sizes in randomized double-blind controlled trials.

Efficacy and Safety of Upadacitinib Versus Dupilumab Treatment for Moderate to Severe Atopic Dermatitis in Four Body Regions: Analysis From the Heads-Up Study.

Upadacitinib has demonstrated high and rapid rates of efficacy in adolescent and adult patients with moderate-to-severe atopic dermatitis (AD) as assessed by the Eczema Area and Severity Index (EASI). This post hoc analysis assessed the EASI response in four anatomical regions for patients with moderate-to-severe AD treated with upadacitinib compared to dupilumab over 24 weeks. Data from patients randomised 1:1 to receive upadacitinib 30 mg extended-release tablet orally once daily or dupilumab 300 mg by subcutaneous injection every 2 weeks after a loading dose of 600 mg in the Heads Up study were analysed for achievement of ≥75%, ≥90%, or 100% reduction of EASI in four body regions: 1) head and neck, 2) trunk (including genitals), 3) upper limbs, and 4) lower limbs (including buttocks) at each study visit through week 24. Patient response data from the Head and Neck Patient Global Impression of Severity (HN-PGIS) were also analysed at each study visit for comparison of upadacitinib to dupilumab. Greater proportions of patients treated with upadacitinib versus dupilumab achieved skin clearance rates of ≥75% (EASI 75) at week 1 and higher clearance rates of ≥90% (EASI 90) or 100% (EASI 100) by week 4 or earlier in all four body regions. This difference was maintained at each visit through week 24 for both EASI 90 and EASI 100. Patient responses on the HN-PGIS indicated that a greater proportion of patients (nominal p-value <0.05) treated with upadacitinib compared to dupilumab reported that AD symptoms in the head and neck region were absent or minimal as early as week 1. Compared to dupilumab, upadacitinib treatment provided higher rates of rapid, sustained efficacy for the head and neck, trunk, upper limbs, and lower limbs for the treatment of moderate-to-severe AD as measured by the EASI and supported by patient responses.

Sudden improvement of alopecia universalis and psoriatic arthritis while receiving upadacitinib: a case-based review.

Alopecia universalis (AU), an advanced form of alopecia areata (AA), is a condition characterized by the complete loss of hair over the entire skin surface. Recent progress has significantly enhanced our understanding of the pathogenesis of AU. In particular, interferon-γ (IFN-γ) and interleukin (IL)-15 seem to play a pivotal role in the pathogenesis of the disease. Nonetheless, a variety of medications has been used to treat the disease with frequently inconsistent results. Given the broad modulation of the immune system and inhibition of key molecules, including IFN-γ and IL-15, oral janus kinase (JAK) inhibitors represent a treatment option for moderate to severe cases of AA, as demonstrated in case reports supporting their efficacy and tolerability. We present the case of a patient suffering from psoriatic arthritis and AU who experienced a sudden improvement in peripheral arthritis and AU while receiving JAK1 selective treatment with upadacitinib. So far, there are very limited case reports of successful upadacitinib treatment for patients with AA, mostly in patients also suffering from atopic dermatitis. Thus, we provide evidence for the efficacy of upadacitinib in managing AU in adults, also in the context of an inflammatory arthritis such as psoriatic arthritis.

Upadacitinib counteracts hepatic lipid deposition via the repression of JAK1/STAT3 signaling and AMPK/autophagy-mediated suppression of ER stress

Upadacitinib (UPA) has been utilized to treat conditions such as rheumatoid arthritis, psoriatic arthritis, atopic dermatitis, ulcerative colitis, Crohn's disease, ankylosing spondylitis, and axial spondyloarthritis by modulating inflammation via the JAK pathway. However, its impact on hepatic lipogenesis remains insufficiently studied. This research evaluated protein expression through Western blotting, lipid accumulation with oil red O staining, autophagosomes in hepatocytes via MDC staining, and hepatic apoptosis via cell viability and caspase 3 activity assays. This study aimed to explore the effects of UPA on hepatic lipogenesis and the underlying molecular mechanisms in in vitro models of hepatic steatosis. These findings demonstrated that UPA reduced lipid deposition, apoptosis, and ER stress in palmitate-treated hepatocytes. UPA treatment inhibited phosphorylated JAK1 and STAT3 while promoting the expression of phosphorylated AMPK and autophagy markers. AMPK siRNA negated the effects of UPA on lipogenic lipid deposition, apoptosis, JAK1/STAT3 phosphorylation, and ER stress. These results reveal that UPAmitigates ER stress through the JAK1/STAT3/AMPK pathway, thereby reducing lipid deposition and apoptosis in hyperlipidemic hepatocytes, supporting its potential as a therapeutic strategy for treating hepatic steatosis in obese individuals.

Effectiveness and safety of upadacitinib retreatment after withdrawal in moderate-to-severe atopic dermatitis: a retrospective study.

Upadacitinib, a janus kinase 1 (JAK1) inhibitor, is effective for moderate-to-severe atopic dermatitis (AD). Upadacitinib treatment may be discontinued in some patients, however, the effectiveness and safety of retreatment after its withdrawal have not been precisely examined in real-world practice. To evaluate the effectiveness and safety of upadacitinib retreatment after withdrawal in real-world clinical practice for Japanese AD patients. This retrospective study included 62 Japanese patients with moderate-to-severe AD treated with upadacitinib 15 mg (n = 38) or 30 mg (n = 24). Effectiveness was assessed using eczema area severity index (EASI) and peak pruritus numerical rating scale (PP-NRS) before treatment (baseline), at time-periods of discontinuation, retreatment, and week 12 after retreatment of upadacitinib. Safety was evaluated through the incidence of treatment-emergent adverse events (TEAE). EASI and PP-NRS scores significantly decreased at week 12 after retreatment of upadacitinib compared to baseline in both 15 mg and 30 mg groups. Achievement rates of EASI 75, EASI 90, and EASI 100 at week 12 after retreatment were 83.8%, 56.8%, and 18.9% in 15 mg group, and 87.0%, 56.5%, and 17.4% in 30 mg group, respectively. TEAEs were mild or moderate, and no serious adverse events or deaths were reported. Retreatment of upadacitinib after withdrawal effectively improved clinical signs and pruritus in patients with AD, with a manageable safety profile, supporting its use for long-term management of AD.

S1081 Effect of Upadacitinib Treatment on Hematological Parameters in Patients With Moderate to Severe Active Crohn’s Disease or Ulcerative Colitis: Pooled Analysis of Phase 3 Induction and Maintenance Studies

S1081 Effect of Upadacitinib Treatment on Hematological Parameters in Patients With Moderate to Severe Active Crohn’s Disease or Ulcerative Colitis: Pooled Analysis of Phase 3 Induction and Maintenance Studies

S1427 A Single Center Experience of Upadacitinib Treatment for Acute Severe Ulcerative Colitis

S1427 A Single Center Experience of Upadacitinib Treatment for Acute Severe Ulcerative Colitis

Erosion regression in patients with rheumatoid arthritis after upadacitinib-a pilot study using high resolution peripheral quantitative computed tomography.

To evaluate whether inhibition of Janus kinases (JAK) 1 could lead to erosion repair on high-resolution peripheral quantitative computer tomography (HR-pQCT) in patients with active rheumatoid arthritis (RA). This was a prospective, non-randomized pilot study. We enrolled 20 adult patients with active RA with ≥1 bone erosion on HR-pQCT. They were given upadacitinib 15 mg once daily for 24 weeks. HR-pQCT of the metacarpophalangeal joint was performed at baseline and 24-week. The serum bone biomarkers level was evaluated before and after treatment. Twenty age-and-sex matched RA patients from another study treated with conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) were included as active controls. Nineteen patients in the upadacitinib group completed the study procedures. After 24 weeks, despite similar improvement in disease activity, a reversed trend in the mean erosion volume change on HR-pQCT was observed comparing the upadacitinib and active control group (upadacitinib group: -0.23 ± 3.26mm3 vs control group: 1.32 ± 6.05mm3, p= 0.131). A greater proportion of erosions in the upadacitinib group demonstrated regression (27% vs 12%, p= 0.085). Using general estimating equation (GEE), the use of upadacitinib was significantly associated with erosion regression (OR: 3.61, 95% CI: 1.00-13.00, p= 0.049) after adjusting for the difference in disease duration. The serum levels of bone resorption markers reduced after upadacitinib treatment. No new safety signal was noted. Despite a similar improvement in RA disease activity after upadacitinib compared with csDMARDs, a differential regression of erosion on HR-pQCT was observed in patients received upadacitinib. The potential role of JAK1 inhibition in erosion repair should be investigated.

Clinical and Ultrasonographic Remission in Bio-naïve and Bio-failure Patients with Rheumatoid Arthritis at 24Weeks of Upadacitinib Treatment: The UPARAREMUS Real-Life Study.

Clinical remission is the main target in the management of patients with rheumatoid arthritis (RA). However, several authors found synovitis in patients with RA in clinical remission at ultrasonography (US). Upadacitinib is a selective Janus kinase1 inhibitor that achieved significantly higher remission rates than adalimumab and abatacept in patients with RA. Here we present the 24-week data of the UPAdacitinib Rheumatoid Arthritis REmission UltraSonography (UPARAREMUS) study. This is a longitudinal multicenter observational study, enrolling bio-naïve and bio-inadequate responder patients affected by RA. The primary endpoint was the proportion of patients achieving both clinical and US remission at week24. The proportion of patients achieving clinical remission with different composite indexes at week12 and 24 was also evaluated. US of four target joints (wrists and second metacarpophalangeal bilaterally) was performed at baseline and weeks12/24, and US remission was defined as the absence of power Doppler (PD) signal ≥ 2 in one target joint, or PD ≥ 1 in two target joints. After 12weeks and 24weeks, 40% and 63.6% of patients achieved US plus clinical remission. The following parameters were associated with US plus clinical remission: being bio-naïve and having a shorter disease duration, although at multivariate analysis significant odds ratio (OR) was found only for being bio-naïve. UPARAREMUS is the first study evaluating the efficacy of upadacitinib in reaching both clinical and US remission in patients with RA. At 24weeks,63.6% of patients reached the primary endpoint, the only baseline associated parameter was being bio-naïve.

Acute generalised exanthematous pustulosis associated with upadacitinib treatment.

Acute generalised exanthematous pustulosis (AGEP) is a rare drug-induced pustular eruption characterised by the rapid onset of superficial pinhead pustules. We discuss the case of a 27-year-old man who presented with a generalised pustular eruption on the neck, trunk and limbs. He commenced upadacitinib for the treatment of atopic dermatitis (AD) 6months before developing the rash, and the dose was increased from 15 to 30mg daily, 3months prior. His only other medication was oral terbinafine, for suspected tinea corporis, which was initiated 1month before developing the pustular eruption. Laboratory investigations showed a mildly raised CRP 25mg/L, neutrophilia 8.22 10×9/L, and a mildly raised ALT 46U/L. A skin biopsy showed subcorneal pustules and a few scattered keratinocytes. Upadacitinib and terbinafine were suspended and the pustular eruption resolved. Updacitinib was reintroduced 3weeks later as the rash was thought to be due to terbinafine and the rash recurred. He was diagnosed with AGEP secondary to upadacitinib. Upadacitinib is a selective JAK inhibitor that is increasingly used for the management of AD and clinicians should be aware that AGEP is a rare but severe adverse effect.

More Time Spent with Clear Skin and No Itch with Upadacitinib versus Dupilumab for Atopic Dermatitis.

Atopic dermatitis (AD), with its hallmark symptoms of pruritus and skin lesions, often impairs patients' quality of life. We assessed time spent with clear/almost clear skin and no/minimal itch during upadacitinib treatment versus placebo or dupilumab among patients with moderate-to-severe AD. This analysis consisted of a post hoc analysis of Measure Up 1 (NCT03569293), Measure Up 2 (NCT03607422), and Heads Up (NCT03738397). Measure Up 1 and 2 were replicate, randomized, double-blind, placebo-controlled phase 3 studies with patients randomized (1:1:1) to once-daily oral upadacitinib 15mg, upadacitinib 30mg, or placebo for 16weeks. Heads Up was a head-to-head, randomized, double-blind, double-dummy, phase 3b study with patients randomized (1:1) to upadacitinib 30mg or subcutaneous dupilumab 300mg for 24weeks. Skin clearance was assessed with the Eczema Area and Severity Index (EASI) at baseline, weeks 1, 2, and 4, and every 4weeks thereafter. Itch was assessed using the Worst Pruritus Numerical Rating Scale (WP-NRS) daily over 16weeks and every 2weeks thereafter to week 24 in Heads Up. This analysis included 1683 patients in Measure Up 1 and 2 and 673 patients in Heads Up. Through 16weeks in Measure Up 1 and 2, patients receiving upadacitinib spent 9.8-13.4 times as many days with an EASI 90 response and 7.0-10.3 times as many days with a WP-NRS 0/1 response versus placebo. In Heads Up, patients receiving upadacitinib spent 2.0 and 1.7 times as many days through 16 and 24weeks, respectively, with an EASI 90 response versus dupilumab. Through 16 and 24weeks, patients receiving upadacitinib spent 3.0 and 2.6 times as many days, respectively, with a WP-NRS 0/1 response versus dupilumab. Patients with moderate-to-severe AD spent more time with clear/almost clear skin and no/minimal itch with upadacitinib versus placebo or dupilumab. ClinicalTrials.gov identifier, Measure Up 1 (NCT03569293), Measure Up 2 (NCT03607422), Heads Up (NCT03738397).

Upadacitinib monotherapy versus methotrexate monotherapy in patients with rheumatoid arthritis: efficacy and safety through 5 years in the SELECT-EARLY randomized controlled trial

BackgroundTo evaluate the efficacy and safety of upadacitinib monotherapy versus methotrexate (MTX) monotherapy over 5 years among MTX-naïve patients with moderately to severely active rheumatoid arthritis (RA) in the long-term extension (LTE) of the phase 3 SELECT-EARLY trial.MethodsPatients were randomized to receive upadacitinib 15 mg or 30 mg or MTX. Patients who did not achieve CDAI remission and had < 20% improvement in tender and swollen joint counts at week 26 received rescue therapy (addition of MTX in the upadacitinib group and addition of upadacitinib in the MTX group). Efficacy assessments were evaluated over 5 years and are reported as observed (AO) for patients who received continuous monotherapy with upadacitinib 15/30 mg or MTX and by randomized group applying non-responder imputation (NRI). Treatment-emergent adverse events (TEAEs) per 100 patient-years were summarized over 5 years.ResultsOf 945 patients randomized and treated, 775 (82%) completed week 48 and entered the LTE on study drug. Higher proportions of patients consistently achieved disease activity targets over 5 years with upadacitinib than MTX. In AO analyses, 53%/59% of patients attained CDAI remission with upadacitinib 15/30 mg versus 43% with MTX at week 260. NRI analyses showed better CDAI, DAS28(CRP), and ACR responses with upadacitinib relative to MTX at week 260 (all comparisons, nominal P < .001). Upadacitinib treatment also resulted in numerically greater inhibition of structural joint progression through week 260 compared to MTX. Most TEAEs, serious AEs, and AEs leading to discontinuation were numerically higher in patients receiving upadacitinib 30 mg. Rates of serious infections, herpes zoster, creatine phosphokinase elevation, nonmelanoma skin cancer, and neutropenia were numerically higher with upadacitinib than MTX. The observed safety profile of upadacitinib over 5 years was consistent with earlier trial results and integrated phase 3 safety analyses.ConclusionsUpadacitinib showed better clinical responses versus MTX in patients with RA throughout the 5-year trial. Higher rates of several AEs were observed with upadacitinib, especially in the 30 mg group, compared to MTX. When used as monotherapy in MTX-naïve patients, the approved upadacitinib 15 mg dose showed better long-term efficacy versus MTX and an overall favorable benefit-risk profile.Trial registrationNCT02706873.

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...

Off-Label Uses of Upadacitinib

Background: Janus Kinase (JAK) inhibitors interfere with the JAK-STAT signaling pathway, which is vital in regulating inflammation and immune function. Notably, upadacitinib, a JAK inhibitor, has been increasingly used as a treatment modality for refractory inflammatory diseases. Methods: A literature review was conducted on Pubmed and Clinical Trials.gov using the keywords “upadacitinib” combined with “off-label”, “dermatology”, “skin”, or “cutaneous” from October 1st, 2021, to October 1st, 2023. 941 articles were reviewed, and 50 articles were included. Results: The systematic search revealed 20 different dermatology conditions treated with off-label use of upadacitinib. Most of these conditions showed drastic improvement by actively decreasing the inflammatory response involved in the pathogenesis of that condition. The most common side effects reported for the medication were elevated creatine kinase, headaches, urinary tract infections, and acne. Patients should also be advised to consider the shingles vaccines prior to upadacitinib treatment. Conclusion: Upadacitinib shows potential utility in the treatment of refractory inflammatory dermatologic conditions, treatment-resistant pruritus, and medication-induced skin reactions. Further large-scale, controlled clinical trials are needed to evaluate the further indications of upadacitinib and its safety profile.

P108 Acne as an adverse effect of upadacitinib treatment for atopic dermatitis in adults and adolescents: a systematic review of short-term analysis

P108 Acne as an adverse effect of upadacitinib treatment for atopic dermatitis in adults and adolescents: a systematic review of short-term analysis