Budget impact and cost per responder analysis of upadacitinib for the treatment of moderate to severe atopic dermatitis from the perspective of the social security and the private sector in Argentina.

OBJECTIVES: Our study assessed the budget impact and cost per responder of upadacitinib15mg and 30 mg for moderate to severe atopic dermatitis (MS-AD) treatment from social security and private health sector perspective in Argentina. METHODS: A budget impact model was adapted to depict clinical and economic aspects of treatment over a 5-years horizon time. Scenario analyses and deterministic sensitivity analyses were performed. A 16-weeks cost per responder model was adapted based on a network meta-analysis. Primary analyses assessed the cost per Eczema Area and Severity Index 50, 75 and 90 at week 16. RESULTS: The inclusion of upadacitinib 15 mg and 30 mg in the biological treatment mix for MS-AD was associated with an average budget saving per-member per-month ofU$S0.062 (social security) and U$S0.064 (private sector). Percentage of patients with access to treatment, acquisition cost of upadacitinib 30 mg and prevalence of MS-AD were the most influential parameters in the budget impact results. At week 16, upadacitinib 30 mg was associated with the lowest number needed to treat and the lowest cost per responder for all outcomes. CONCLUSION: The introduction of upadacitinib in MS-AD treatment was associated with modest savings for the social security and private payer budget in Argentina.

Oral Janus Kinase Inhibitors in Pediatric Atopic Dermatitis.

PURPOSE OF REVIEW: To analyze the efficacy and safety of Janus kinase inhibitors (JAKi) in the treatment of pediatric AD. RECENT FINDINGS: Adolescents with moderate and severe atopic dermatitis (AD) need systemic therapies, as stated several recent practice guidelines. (JAKi) have shown their efficacy in the treatment of adult AD, however, there is a lack of information concerning efficacy and safety of their use in pediatric AD. We found that the JAKi's abrocitinib (ABRO), baricitinib (BARI), and upadacitinib (UPA), are all an effective treatment option with a very fast onset of action for adolescents with moderate-to-severe AD. BARI was not effective in children between 2 and 10 years with moderate-to-severe AD. Fortunately, major safety issues with JAKi in adolescents with AD have not been documented in the trials, so far, contrasting with the reports in adults with AD, where these events have very rarely occurred. There are some reports of herpes zoster (HZ) infection in adolescents on JAKi, but it is not a major safety concern. Acne is a relatively common AE with UPA in adolescents; however, it is responsive to standard treatment. This review will help the clinician to choose among the JAKi according to the needs and clinical features of patients with moderate and severe AD. In the following years, with the advent of new biologicals and JAKi, these therapies will fall into place in each phase of the evolution of patients with AD.

Successful treatment of severe atopic dermatitis and alopecia universalis with upadacitinib in a 29-year-old male patient.

A 29-year-old male patient had severe atopic dermatitis (AD) and alopecia universalis (AU) that could not be controlled by using classic therapy. He started taking upadacitinib and achieved an excellent response for both his AD and AU. Thus, upadacitinib represents a promising therapeutic approach for patients with severe AD and alopecia areata.

Safety of Upadacitinib in Immune-Mediated Inflammatory Diseases: Systematic Literature Review of Indirect and Direct Treatment Comparisons of Randomized Controlled Trials.

INTRODUCTION: Immune-mediated inflammatory diseases including rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), non-radiographic axial spondylarthritis (nr-axSpA), atopic dermatitis (AD), ulcerative colitis (UC), and Crohn's disease (CD) pose a substantial burden on patients and their quality of life. Upadacitinib is an orally administered, selective, and reversible Janus kinase inhibitor indicated for seven conditions, but data on its safety versus other active treatments are limited. A systematic literature review of indirect and direct treatment comparisons of randomized controlled trials (RCTs) was conducted to assess the safety profile of upadacitinib. METHODS: MEDLINE, Embase, and Cochrane Library databases were searched for indirect and direct treatment comparisons of RCTs that (1) included licensed upadacitinib dosages; (2) studied any of the seven conditions; (3) reported any adverse events (AEs), serious AEs (SAEs), AEs leading to discontinuation, major adverse cardiovascular event, venous thromboembolism, malignancies, infections or serious infections, and death; and (4) were published between January 2018 and August 2022. RESULTS: A total of 25 studies were eligible for inclusion. SAEs, AEs leading to discontinuation, and any AEs were commonly studied. RA was the most studied condition, followed by AD and UC. Most studies (16/25, 64%) reported no statistically significant difference in the studied safety outcomes between upadacitinib and other active treatments (e.g., tumor necrosis factor blockers, interleukin receptor antagonists, integrin receptor antagonists, T cell co-stimulation modulator), or placebo (placebo ± methotrexate or topical corticosteroids). Other studies (9/25, 36%) reported mixed results of no statistically significant difference and either statistically higher (8/25, 32%) or lower rates (1/25, 4%) on upadacitinib. CONCLUSION: Most studies suggested that upadacitinib has no statistically significant difference in the studied safety outcomes compared to active treatments or placebo in patients with RA, PsA, AS, AD, UC, and CD. A few studies reported higher rates, but findings were inconsistent with limited interpretation.

Impacto presupuestario de upadacitinib en pacientes con artritis reumatoide moderada a severa en Argentina / Budget impact of upadacitinib in patients with moderate to severe rheumatoid arthritis in Argentina

OBJETIVOS. Analizar el impacto presupuestario de upadacitinib (UPA) 15 mg + metotrexato (MTX) para el tratamiento de la artritis reumatoide (AR) moderada a grave en pacientes con respuesta inadecuada a los fármacos antirreumáticos modificadores de la enfermedad convencionales (RI-DMARc) desde la perspectiva de la seguridad social y los sectores de salud privados en Argentina. MATERIALES Y METODOS. Se desarrolló un modelo de análisis de impacto presupuestario para una cohorte hipotética de 100,000 adultos con cobertura de seguro de salud que fueron diagnosticados con AR en un horizonte de tiempo de 5 años. Los parámetros del modelo se obtuvieron a través de una revisión de la literatura y se validaron con expertos locales. Los costos se expresan en dólares estadounidenses (USD) para el 2024. RESULTADOS. La introducción de UPA 15 mg + MTX para el tratamiento de AR moderada a grave y RI-DMARc resultó en un costo incremental mínimo, con un costo acumulado total a cinco años de USD 1.855 para la seguridad social y USD 1.812 para el sector privado de salud, lo que representa aproximadamente el 2% del presupuesto total. El costo de adquisición de UPA fue la variable más influyente en el análisis de sensibilidad. CONCLUSIONES.La introducción de UPA 15 mg + MTX para el tratamiento de AR genera un incremento de costos marginal para el sistema de salud en Argentina, lo cual es especialmente importante en contextos de presupuestos limitados. Proporcionar estimaciones basadas en la evidencia es una herramienta valiosa para ayudar a tomar decisiones informadas sobre la asignación eficiente de recursos en salud.

Safety of upadacitinib in Latin American patients with rheumatoid arthritis: an integrated safety analysis of the SELECT phase 3 clinical program.

INTRODUCTION/OBJECTIVES: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by ongoing inflammation and degradation of synovial joints. The oral JAK inhibitor, upadacitinib, is approved for RA. We conducted an integrated safety analysis of upadacitinib 15 mg once daily (QD) in patients from Latin America (LATAM) versus the rest of the world (RoW). METHODS: Treatment-emergent adverse events (AEs) and laboratory data from six phase 3, randomized controlled trials, adjusted for upadacitinib 15 mg QD use in RA, were analyzed. RESULTS: Overall, 3209 patients received upadacitinib 15 mg QD for 7024 patient-years (PY). LATAM patients (n = 725) had a mean upadacitinib exposure of 1518 PY. Baseline characteristics were generally similar between LATAM and RoW populations. AE rates (including serious/opportunistic infections, tuberculosis, and herpes zoster) and deaths were comparable between populations. LATAM patients had lower serious AE rates per 100 PY (9.4 vs 14.0 E/100 PY) and discontinuation-related AEs (3.9 vs 6.0 E/100 PY) versus RoW. Rates of cardiovascular events were low (≤ 0.5 E/100 PY) and similar between populations. Malignancies, excluding non-melanoma skin cancer, were less common in the LATAM population versus RoW (0.2 vs 1.0 E/100 PY). Laboratory abnormalities were similar between populations, with decreases in hemoglobin, lymphocyte, and neutrophil counts, and elevations in liver enzymes and creatine phosphokinase. Mean change from baseline in low- and high-density lipoprotein cholesterol was generally comparable between LATAM and RoW populations. CONCLUSION: Upadacitinib 15 mg QD demonstrated a consistent safety profile across LATAM and RoW patient populations, with no new safety risks observed. TRIAL REGISTRATION NUMBERS: SELECT-EARLY, NCT02706873; SELECT-NEXT, NCT02675426; SELECT-COMPARE, NCT02629159; SELECT-MONOTHERAPY, NCT02706951; SELECT-BEYOND, NCT02706847; SELECT-CHOICE, NCT03086343.

Evaluating upadacitinib for the treatment of rheumatoid arthritis.

INTRODUCTION: The introduction of JAKs inhibitors for the treatment of rheumatoid arthritis represents a promising new era in the management of the disease. New compounds under investigation, like upadacitinib, with greater selectivity for JAK1 inhibition have recently been approved for the treatment of adults with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to conventional synthetic disease-modifying antirheumatic drugs. AREAS COVERED: Herein, the authors review the pharmacological data, the therapeutic efficacy, and safety data of upadacitinib before providing the reader with their critical evaluation and future perspectives. EXPERT OPINION: Upadacitinib was able to accomplish all the primary and secondary end points in most of the trials, with a safety profile that is similar to the other JAK inhibitors. It has also demonstrated superiority over a tumor necrosis factor inhibitor and data on new indications is also favorable. Upadacitinib is a promising new drug for the treatment of rheumatoid arthritis. GLOSSARY: Adalimumab: ADA; American College of Rheumatology: ACR; Assessment of Spondylarthritis International Society 40: ASAS40; Ankylosis Spondylitis: AS; Area under the Curve: AUC; Biological Disease-modifying arthritis drugs: bDMARDs; Clinical disease activity index: CDAI; C Reactive Protein: CRP; Conventional Synthetic Disease-modifying arthritis drugs: csDMARDs; Deep Venous Thrombosis: DVT; Disease arthritis score: DAS.