Upadacitinib in Active Non-radiographic Axial Spondyloarthritis: 1-Year Data From a Double-Blind, Randomized, Placebo-Controlled, Phase 3 Trial.

OBJECTIVE: Upadacitinib improved the signs and symptoms of non-radiographic axial spondyloarthritis (nr-axSpA) versus placebo over 14 weeks in the primary analysis of the SELECT-AXIS 2 nr-axSpA study. Here, we evaluated the efficacy and safety of upadacitinib through 1 year in patients with nr-axSpA in SELECT-AXIS 2. METHODS: Patients aged at least 18 years diagnosed with nr-axSpA who fulfilled the 2009 Assessment of SpondyloArthritis International Society (ASAS) classification criteria and were receiving stable background therapy were randomized to upadacitinib 15 mg once daily or placebo for the 52-week double-blind period. Efficacy was assessed using non-responder imputation incorporating multiple imputation (NRI-MI) and as-observed analyses for binary endpoints, and mixed-effects model repeated measures for continuous endpoints. RESULTS: Of 314 randomized patients, 259 (upadacitinib, n = 129; placebo, n = 130) completed 52 weeks of treatment. More patients receiving upadacitinib versus placebo achieved ≥40% improvement in ASAS at week 52 (63% vs 43%, NRI-MI; nominal P < 0.001). Similar treatment effects were observed for the achievement of axSpA Disease Activity Score inactive disease (33% v 11%, NRI-MI; nominal P < 0.001). Overall, patients receiving upadacitinib versus placebo showed greater improvement in disease activity, inflammation, pain, function, enthesitis, and quality of life through 52 weeks. Adverse events were generally comparable between the treatment groups. No opportunistic infections, malignancies, major adverse cardiovascular events, venous thromboembolic events, inflammatory bowel disease, or deaths were reported in those receiving upadacitinib. CONCLUSION: Treatment with upadacitinib showed sustained efficacy versus placebo with no new safety findings identified through 1 year. These results support the continued favorable benefit-risk profile of upadacitinib treatment for nr-axSpA.

A preliminary survey of rheumatologists on the management of late-onset rheumatoid arthritis in Japan.

Objectives We investigated the current perspectives regarding the management of late-onset rheumatoid arthritis (LORA) among rheumatologists in clinical practice. Methods This study was performed in October 2021, and included 65 rheumatologists certified by the Japan College of Rheumatology, who were administered questionnaires (including multiple choice and descriptive formulae) regarding the management of LORA. We aggregated and analyzed the responses. Results All 65 rheumatologists responded to the survey; 47 (72%) answered that >50% of newly diagnosed patients were aged ≥65 years, 42 (65%) answered that achievement of remission or low disease activity was the treatment goal, and 40 (62%) considered patient safety to be the highest priority. Most rheumatologists are concerned about the management of conditions other than RA, such as comorbidities, financial constraints, and life circumstances that interfere with standard or recommended treatment implementation. Conclusion This preliminary survey highlighted various rheumatologists' perspectives regarding the management of LORA.

Effect of Secukinumab Versus Adalimumab Biosimilar on Radiographic Progression in Patients With Radiographic Axial Spondyloarthritis: Results From a Head-to-Head Randomized Phase IIIb Study.

OBJECTIVE: Spinal radiographic progression is an important outcome in radiographic axial spondyloarthritis (SpA). The objective of the phase IIIb SURPASS study was to compare spinal radiographic progression in patients with radiographic axial SpA treated with secukinumab (interleukin-17A inhibitor) versus adalimumab biosimilar (Sandoz adalimumab [SDZ-ADL]; tumor necrosis factor inhibitor). METHODS: Biologic-naive patients with active radiographic axial SpA, at high risk of radiographic progression (high-sensitivity C-reactive protein [hsCRP] ≥5 mg/L and/or ≥1 syndesmophyte[s] on spinal radiographs), were randomized (1:1:1) to secukinumab (150/300 mg) or SDZ-ADL (40 mg). The proportion of patients with no radiographic progression (change from baseline [CFB] in modified Stoke Ankylosing Spondylitis Spinal Score [mSASSS] ≤0.5) on secukinumab versus SDZ-ADL at week 104 (primary endpoint), mean CFB-mSASSS, proportion of patients with ≥1 syndesmophyte(s) at baseline with no new syndesmophyte(s), and safety were evaluated. RESULTS: Overall, 859 patients (78.5% male, mSASSS 16.6, Bath Ankylosing Spondylitis Disease Activity Index 7.1, hsCRP 20.4 mg/L, and 73.0% with ≥1 syndesmophyte[s]) received secukinumab 150 mg (n = 287), secukinumab 300 mg (n = 286), or SDZ-ADL (n = 286). At week 104, the proportion of patients with no radiographic progression was 66.1%, 66.9%, and 65.6% (P = not significant, both secukinumab doses) and mean CFB-mSASSS was 0.54, 0.55, and 0.72 in secukinumab 150 mg, secukinumab 300 mg, and SDZ-ADL arms, respectively. Overall, 56.9%, 53.8%, and 53.3% of patients on secukinumab 150 mg, secukinumab 300 mg, and SDZ-ADL, respectively, with ≥1 syndesmophyte(s) at baseline did not develop new syndesmophyte(s) by week 104. There were no unexpected safety findings. CONCLUSION: Spinal radiographic progression over two years was low with no significant difference between secukinumab and SDZ-ADL arms. The safety of both treatments was consistent with previous reports.

Consensus statement on the management of late-onset rheumatoid arthritis.

OBJECTIVES: Late-onset rheumatoid arthritis (LORA), which has been increasing in recent years, lacks evidence for initial treatment. Japanese rheumatology experts recognized this gap and addressed it by developing consensus statements on the first clinical application of LORA. METHODS: These statements were created following an introductory discussion about treatment fundamentals, which included a review of existing literature and cohort data. The steering committee created a draft, which was refined using a modified Delphi method that involved panel members reaching a consensus. The panel made decisions based on input from geriatric experts, clinical epidemiologists, guideline developers, patient groups, and the LORA Research Subcommittee of the Japan College of Rheumatology. RESULTS: The consensus identified four established facts, three basic approaches, and six expert opinions for managing LORA. Methotrexate was recommended as the primary treatment, with molecular-targeted agents being considered if treatment goals cannot be achieved. An emphasis was placed on assessing the lives of older patients due to challenges in risk management and methotrexate accessibility caused by comorbidities or cognitive decline. CONCLUSIONS: The experts substantiated and refined 13 statements for the initial treatment of LORA. To validate these claims, the next is to conduct a registry study focusing on new LORA cases.

Changes in alcohol intake and serum urate changes: longitudinal analyses of annual medical examination database.

INTRODUCTION: Despite the established cross-sectional association between alcohol intake and serum urate (SU), its longitudinal association remains unknown. This study aimed to determine whether changes in alcohol intake have a clinically relevant association with SU change. METHOD: We conducted retrospective analyses using systematically collected annual medical examination data from October 2012 to October 2022 in a Japanese preventive medicine centre. The exposure was changes in alcohol intake between two consecutive visits. The association of SU changes with alcohol intake changes was estimated by mixed-effect linear regression with adjustment for relevant covariates. RESULTS: We analysed 63 486 participants (median age, 47.0 years; 55% women; 58.6% regular alcohol drinkers with a median of 1.4 drinks/day) with 370 572 visits. The median SU level was 5.3 mg/dL, and 506 (0.8%) participants had diagnoses of gout or hyperuricemia without medication use during the study period. Decreasing one daily alcohol intake had a clinically small association with SU changes (-0.019 (95% CI: -0.021 to -0.017) mg/dL). Beer had the largest association with SU (-0.036 (95% CI: -0.039 to -0.032) mg/dL for one beer decrease). Complete discontinuation of any alcohol from a mean of 0.8 drinks/day was associated with -0.056 mg/dL (95% CI: -0.068 to -0.043) decrease in SU; the association became larger in hyperuricemic participants (-0.110 mg/dL (95% CI: -0.154 to -0.066) for alcohol discontinuation from a mean of 1.0 drinks/day). CONCLUSIONS: This study revealed changes in alcohol intake had small associations with SU change at the general Japanese population level. Complete discontinuation of alcohol in hyperuricemic participants had only modest improvement in SU.

Earlier clinical response predicts low rates of radiographic progression in biologic-naïve patients with active psoriatic arthritis receiving guselkumab treatment.

OBJECTIVE: Assess relationship between earlier clinical improvement and radiographic progression (RP) over 2 years in guselkumab-treated patients with active psoriatic arthritis (PsA). METHOD: Post hoc analyses combined data from DISCOVER-2 biologic-naïve adults with active PsA randomized to either guselkumab 100 mg every 4 weeks (Q4W) or guselkumab at W0, W4, then Q8W. Correlations (Spearman's coefficient) between baseline disease parameters and total PsA-modified van der Heijde-Sharp (vdH-S) score were examined. Repeated-measures mixed models, adjusted for known RP risk factors, assessed the relationship between Disease Activity Index in PsA (DAPSA) improvement, DAPSA improvement exceeding the median or the minimal clinically important difference (MCID), or DAPSA low disease activity (LDA) at W8 and RP rate, assessed by change from baseline in vdH-S score through W100. RESULTS: Baseline age, PsA duration, CRP level, and swollen joint count, but not psoriasis duration/severity, weakly correlated with baseline vdH-S score. Elevated baseline CRP (parameter estimate [ß] = 0.17-0.18, p < 0.03) and vdH-S score (ß = 0.02, p < 0.0001) significantly associated with greater RP through W100. Greater improvement in DAPSA (ß = -0.03, p = 0.0096), achievement of DAPSA improvement > median (least squares mean [LSM] difference: -0.66, p = 0.0405) or > MCID (-0.67, p = 0.0610), or DAPSA LDA (-1.44, p = 0.0151) by W8 with guselkumab significantly associated with less RP through W100. The effect of W8 DAPSA LDA on future RP was strengthened over time among achievers vs. non-achievers (LSM difference enhanced from -1.05 [p = 0.0267] at W52 to -1.84 [p = 0.0154] at W100). CONCLUSIONS: In guselkumab-treated patients with active PsA, earlier improvement in joint symptoms significantly associated with lower RP rates through 2 years, indicating blockade of the IL-23 pathway may modify long-term disease course and prevent further joint damage. Key Points • Greater improvement in DAPSA at Week 8 of guselkumab treatment was significantly associated with less progression of structural joint damage at 2 years in patients with active psoriatic arthritis (PsA). • Early control of peripheral joint disease activity with blockade of the IL-23 pathway may modify long-term PsA trajectory and prevent further joint damage.

Upadacitinib for the treatment of adults with active non-radiographic axial spondyloarthritis (nr-axSpA).

INTRODUCTION: Non-radiographic axial spondyloarthritis (nr-axSpA) is a chronic inflammatory condition with axial and peripheral musculoskeletal involvement, fulfilling criteria of axSpA in the absence of advanced radiographic sacroiliitis. While appropriate treatment is required for chronic pain and disability resulting from disease progression, the limited availability of treatment options becomes evident. Upadacitinib, an oral selective Janus kinase 1 inhibitor, was approved in Europe, the United States, and other countries for management of nr-axSpA with inadequate response to existing therapies. AREA COVERED: This review summarizes essential drug profiles, efficacy, and safety of upadacitinib for nr-axSpA in conjunction with data pertaining to radiographic axSpA. EXPERT OPINION: In a phase 3 trial, upadacitinib exhibited efficacy for patients with nr-axSpA, irrespective of prior exposures to biological disease-modifying antirheumatic drugs (bDMARDs). The safety profiles of upadacitinib in nr-axSpA mirrored those in other indications, underscoring its potential as a promising treatment option for nr-axSpA. Concurrently, physicians should be aware of the absence of real-world data, longitudinal efficacy and safety, direct comparative studies between upadacitinib and bDMARDs in nr-axSpA, and evidence for precision medicine to identify patients who may optimally benefit from upadacitinib over bDMARDs. Future research is imperative to facilitate the effective utilization of upadacitinib in daily clinical practice.

Disease-modifying effect and long-term safety of belimumab in patients with systemic lupus erythematosus: A single-center retrospective study.

BACKGROUND: Disease modification in systemic lupus erythematosus (SLE) is important for minimizing disease activity while limiting treatment-associated toxicities. Belimumab can be used as a remission-induction/maintenance systemic lupus erythematosus therapy; however, its disease-modifying effects are unclear. We aimed to determine these effects in patients with systemic lupus erythematosus. METHODS: This single-center retrospective cohort study included 92 patients with systemic lupus erythematosus treated with belimumab. We analyzed the changes in flare free rate/lupus low disease activity state (LLDAS) attainment rate/glucocorticoid dosage/Systemic Lupus International Collaborating Clinics and American College of Rheumatology damage index (SDI) score/drug retention rate after treatment initiation. RESULTS: Fifty-two weeks after initiating belimumab, the flare rate decreased from 82.6% to 14.1% (p < .01). Until week 52 and 1000 days after initiating belimumab treatment, > 70% and ∼90% of the patients attained lupus low disease activity state, respectively. Belimumab treatment significantly reduced glucocorticoid demand (initiation day, 8.88 (6.00-15.00) mg/d; week 52, 5.00 (2.00-7.00) mg/d; final day of the study period, 3.00 (0.46-6.06) mg/d, initiation day vs. week 52: p < .01, initiation day vs. final day: p < .01); at the end of the study period, 68.5% of patients required ≤5 mg/d prednisolone, and 22.8% discontinued glucocorticoids. Most patients were SDI progression-free (week 52, ∼95%; day 1000, ∼90%), and belimumab showed a high drug retention rate (week 52, 90%; day 1000 > 80%). CONCLUSION: Most patients experienced lupus low disease activity state, reduced flare rate and glucocorticoid demand, and a stable SDI trend after belimumab treatment initiation. Given its efficacy and retention rate, belimumab treatment may serve as a fundamental strategy in disease modification.

Efficient detection of somatic UBA1 variants and clinical scoring system predicting patients with variants in VEXAS syndrome.

OBJECTIVES: To efficiently detect somatic UBA1 variants and establish a clinical scoring system predicting patients with pathogenic variants in VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome. METHODS: Eighty-nine Japanese patients with clinically suspected VEXAS syndrome were recruited [81 males and 8 females; median onset age (IQR) 69.3 years (62.1-77.6)]. Peptide nucleic acid-clamping PCR (PNA-PCR), regular PCR targeting exon 3 clustering UBA1 variants, and subsequent Sanger sequencing were conducted for variant screening. Partitioning digital PCR (pdPCR) or targeted amplicon deep sequencing (TAS) was also performed to evaluate the variant allele frequency (VAF). We developed our clinical scoring system to predict UBA1 variant-positive and ­negative patients and assessed the diagnostic value of our system using receiver operating characteristic (ROC) curve analysis. RESULTS: Forty patients with reported pathogenic UBA1 variants (40/89, 44.9%) were identified, including a case having a variant with VAF of 1.7%, using a highly sensitive method. Our clinical scoring system considering >50 years of age, cutaneous lesions, lung involvement, chondritis, and macrocytic anaemia efficiently predicted patients with UBA1 variants (the area under the curve for the scoring total was 0.908). CONCLUSIONS: Genetic screening with the combination of regular PCR and PNA-PCR detected somatic UBA1 variants with high sensitivity and specificity. Our scoring system could efficiently predict patients with UBA1 variants.

Effect of Upadacitinib on Quality of Life and Work Productivity in Active Non-radiographic Axial Spondyloarthritis: Results From Randomized Phase 3 Trial SELECT-AXIS 2.

INTRODUCTION: To evaluate the effect of upadacitinib vs. placebo on health-related quality of life (HRQoL) and work productivity in patients with active non-radiographic axial spondyloarthritis (nr-axSpA) enrolled in the SELECT-AXIS 2 phase 3 randomized controlled trial. METHODS: Adult patients with active nr-axSpA and an inadequate response to non-steroidal anti-inflammatory drugs were randomized 1:1 to receive upadacitinib 15 mg once daily or placebo. Mean changes from baseline in measures of HRQoL (Ankylosing Spondylitis QoL [ASQoL], Assessment of SpondyloArthritis international Society Health Index [ASAS HI], Short-Form 36 Physical Component Summary [SF-36 PCS] score) and Work Productivity and Activity Impairment (WPAI) were assessed through 14 weeks based on mixed-effects repeated measures or analysis of covariance models. The proportions of patients with improvements ≥ minimum clinically important differences (MCID) were assessed in HRQoL measures at week 14 using non-responder imputation with multiple imputation. RESULTS: At week 14, upadacitinib- vs. placebo-treated patients reported greater improvements from baseline in ASQoL and ASAS HI (ranked, P < 0.001) and in SF-36 PCS and WPAI overall work impairment (nominal P < 0.05). Improvements were observed as early as week 2 in ASAS HI. Greater proportions of upadacitinib vs. placebo-treated patients reported improvements ≥ MCID in ASQoL (62.6 vs. 40.9%), ASAS HI (44.8 vs. 28.8%), and SF-36 PCS (69.3 vs. 52.0%), with numbers needed to treat < 10 for all (nominal P ≤ 0.01). Improvements ≥ MCID were consistently observed irrespectively of prior exposure to tumor necrosis factor inhibitors. CONCLUSIONS: Upadacitinib provides clinically meaningful improvements in HRQoL and work productivity in patients with active nr-axSpA. CLINICAL REGISTRATION NUMBER: NCT04169373, SELECT-AXIS 2.

Current evidence and practical knowledge for ultrasound-guided procedures in rheumatology: Joint aspiration, injection, and other applications.

Ultrasound (US)-guided procedures have increasingly gained their role in the daily practice of rheumatology, owing to the growing evidence supporting their utility. The utilization of US guidance in procedures may enhance their accuracy, efficacy, and safety. This article presents a comprehensive review of the current evidence and practical knowledge pertaining to US-guided procedures in rheumatology, encompassing joint aspirations, injections, and other applications such as tendon sheath injections. We provide a detailed description of the US-guided procedure process and compare the in-plane and out-of-plane view methods, along with practical techniques based on existing evidence or our own expertise. For each joint, we summarize how to perform procedures with figures to facilitate a better understanding. Additionally, we introduce other applications of US-guided procedures for tendons, enthesis, bursae, and nerves as well as emerging therapies such as US-guided fascia hydrorelease. By utilizing these US techniques, rheumatologists can achieve the ability to manage a wider range of musculoskeletal conditions.

Patient-Physician Communication and Perception of Treatment Goals in Rheumatoid Arthritis: An Online Survey of Patients and Physicians.

INTRODUCTION: To evaluate patient-physician communication and patients' understanding of treatment goals in rheumatoid arthritis (RA). METHODS: A cross-sectional online survey of patients with RA and physicians treating RA was conducted between 16 and 30 June 2021. Participants were asked to rate the importance of 17 goals on a 6-point Likert scale, and mean scores were compared between patients and physicians by the Wilcoxon rank sum test. Patients' satisfaction with physician communication and their understanding of treatment goals were also assessed. RESULTS: The responses of 502 patients and 216 physicians were analyzed. The most common patient age group was 50-59 years (28.5%), and the mean disease duration was 10.3 years. Physicians had a mean of 19.2 years of treatment experience and were treating a mean of 44.3 patients. Among the 17 goals assessed, patients placed significantly more importance on drug tapering or discontinuation as short-term goals (3-6 months) and on performing basic activities of daily living, being able to engage in daily tasks, achieving and maintaining remission, maintaining better laboratory values, and drug tapering or discontinuation as long-term goals (5-10 years; all adjusted p < 0.05). Patient treatment satisfaction was significantly associated with disease activity, a feeling of treatment effectiveness, satisfaction with physician communication, and agreement with physician goals. CONCLUSION: Differences exist among patients with RA and physicians treating RA regarding the importance of short- and long-term treatment goals. Good patient-physician communication appears to be important for improving patient satisfaction. TRIAL REGISTRATION: University Hospital Medical Information Network identifier: UMIN000044463.

Differences in the Association Between Alcoholic Beverage Type and Serum Urate Levels Using Standardized Ethanol Content.

Importance: Differences have been observed in the association of serum urate levels with consumption of different types of alcoholic beverages. However, previous studies have not standardized the unit of intake for ethanol content, and only limited types of alcoholic beverages have been evaluated. Objective: To examine differences in the association of serum urate levels with various types of alcoholic beverages when their intakes are standardized for ethanol content. Design, Setting, and Participants: This retrospective cross-sectional study was conducted using data from participants aged 20 years or older who completed a medical checkup at St Luke's International University in Japan between October 1, 2012, and October 31, 2021. Participant demographics, blood test results, and lifestyle questionnaire data were used as covariates. Analysis was performed in December 2021. Exposures: Consumption of alcoholic beverages, including beer, sake (rice wine), shochu (Japanese spirit), wine, and whiskey. Main Outcomes and Measures: Serum urate levels were measured during the medical checkup. The beverage unit was standardized to 1 standard drink, which contained 20 g of ethanol. Multivariable linear regression including interaction terms of alcohol consumption and dominant alcoholic beverage was performed. Results: This study included 78 153 participants. Their mean (SD) age was 47.6 (12.8) years; 36 463 (46.7%) were men and 41 690 were women (53.3%). A total of 45 755 participants (58.5%) were regular alcohol drinkers. Consistent associations of serum urate levels with alcohol consumption were observed in the beer-dominant group, with ß coefficients (for 1 standard drink per day) of 0.14 mg/dL (95% CI, 0.11-0.17 mg/dL; P < .001) for men and 0.23 mg/dL (95% CI, 0.20-0.26 mg/dL; P < .001) for women. A moderate increase in serum urate levels was observed in the wine-dominant group compared with a modest and nonsignificant increase in the sake-dominant group, with ß coefficients (for 1 standard drink per day) for the latter group of 0.05 mg/dL (95% CI, -0.01 to 0.10; P = .10) for men and 0.04 mg/dL (95% CI, -0.05 to 0.14 mg/dL; P = .38) for women. Restricted cubic splines showed different patterns in associations of serum urate levels with ethanol intake by dominant alcoholic beverages. Conclusions and Relevance: The results of this study suggest that the extent of the association of serum urate levels with alcohol intake was different for alcoholic beverages even after ethanol content was standardized. Higher beer consumption among men and women was consistently associated with higher serum urate levels, whereas sake was not associated with changes in serum urate levels. Therefore, alcoholic beverage type, in addition to ethanol content, should be considered as a factor contributing to hyperuricemia.

Socioeconomic impact of treatment with biological disease-modifying antirheumatic drugs in Japanese patients with rheumatoid arthritis.

OBJECTIVES: We evaluate the socioeconomic impact of treatment with biological and targeted synthetic disease-modifying antirheumatic drugs in Japanese patients with rheumatoid arthritis. METHODS: We analysed data retrospectively from the prospective observational CorEvitas RA Japan Registry (March 2016-February 2020). Patients were categorised into paid workers (PWs) and home workers (HWs) and further based on drug classes. We assessed medication persistence, treatment outcomes, health care resource utilisation, and socioeconomic impact over 12 months, including direct (drugs and health care resource utilisation) and indirect (loss of productivity) costs. RESULTS: Overall, 187 PWs and 114 HWs were identified. Over 12 months, medication persistence was high, treatment outcomes improved, and outpatient visits reduced in both groups. Following treatment initiation, direct costs increased, whereas indirect (loss of productivity) costs decreased in both groups. The unadjusted socioeconomic impact [Japanese yen (JPY)] increased across all drug classes in PWs (range: 29,700-151,700) and HWs (range: -28,700 to 83,000). Adjusted change in monthly socioeconomic impact was JPY 29,700-138,900 for PWs and JPY -28,000 to 92,800 for HWs. CONCLUSIONS: In this study of Japanese patients with rheumatoid arthritis, the socioeconomic burden increased across patient groups and drug classes. The decrease in indirect (loss of productivity) costs partially offset the increase in direct costs.

Evaluation of VTE, MACE, and Serious Infections Among Patients with RA Treated with Baricitinib Compared to TNFi: A Multi-Database Study of Patients in Routine Care Using Disease Registries and Claims Databases.

INTRODUCTION: The aim of this work is to evaluate baricitinib safety with respect to venous thromboembolism (VTE), major adverse cardiovascular events (MACE), and serious infection relative to tumor necrosis factor inhibitors (TNFi) in patients with rheumatoid arthritis (RA). METHODS: Patients with RA from 14 real-world data sources (three disease registries, eight commercial and three government health insurance claims databases) in the United States (n = 9), Europe (n = 3), and Japan (n = 2) were analyzed using a new user active comparator design. Propensity score matching (1:1) controlled for potential confounding. Meta-analysis of incidence rate ratios (IRR) and incidence rate differences (IRD) for each outcome, from each data source was executed using modified Poisson regression and Cochran-Mantel-Haenszel analysis. RESULTS: Of 9013 eligible baricitinib-treated patients, 7606 were propensity score-matched with TNFi-treated patients, contributing 5879 and 6512 person-years of baricitinib and TNFi exposure, respectively. Across data sources, 97 patients (56 baricitinib) experienced VTE during follow-up, 93 experienced MACE (54 baricitinib), and 321 experienced serious infection (176 baricitinib). Overall IRRs comparing baricitinib with TNFi treatment were 1.51 (95% CI 1.10, 2.08) for VTE, 1.54 (95% CI 0.93, 2.54) for MACE, and 1.36 (95% CI 0.86, 2.13) for serious infection. IRDs for VTE, MACE, and serious infection, respectively, were 0.26 (95% CI -0.04, 0.57), 0.22 (95% CI -0.07, 0.52), and 0.57 (95% CI -0.07, 1.21) per 100 person-years greater for baricitinib than TNFi. CONCLUSIONS: Overall results suggest increased risk of VTE with baricitinib versus TNFi, with consistent point estimates from the two largest data sources. A numerically greater risk was observed for MACE and serious infection when comparing baricitinib versus TNFi, with different point estimates from the two largest data sources. Findings from this study and their impact on clinical practice should be considered in context of limitations and other evidence regarding the safety and efficacy of baricitinib and other Janus kinase inhibitors. TRIAL REGISTRATION: EU PAS Register ( http://encepp.eu ), identifier #32271.

Upadacitinib for moderate-to-severe atopic dermatitis, in adults and adolescents 12 years and older: review of international and Japanese populations.

INTRODUCTION: Atopic dermatitis is one of the most prevalent chronic skin diseases. Topical therapies continue to be the mainstay of treatment but are limited by noncompliance and side-effects from inappropriate or long-term use. Systemic therapies including cyclosporine and dupilumab have been the treatments of choice for refractory cases. However, outcomes may remain less than satisfactory, and cyclosporine use is further limited by nephrotoxicity.Upadacitinib, an oral Janus kinase inhibitor, is widely used for treating rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis and has recently received approval for atopic dermatitis in the United States, Europe, Japan, and other countries. These approvals were based on results from several randomized controlled trials in which upadacitinib demonstrated better and faster response versus placebo or dupilumab. AREA COVERED: Therapies for atopic dermatitis are reviewed, with emphasis on drug profile, efficacy, and safety profile of upadacitinib for atopic dermatitis. In the review of the clinical trials, special focus is placed on efficacy in the Japanese population. EXPERT OPINION: Currently, there are several treatment options for atopic dermatitis refractory to topical therapies. However, appropriate utilization of Janus kinase inhibitors in clinical practice remains challenging, especially with regard to proper case selection, optimal timing, and appropriateness of use.

Management of Psoriatic Arthritis in Patients With Comorbidities: An Updated Literature Review Informing the 2021 GRAPPA Treatment Recommendations.

OBJECTIVE: The 2021 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) treatment recommendations provide an evidence-based guide for selecting therapy based on the individual's disease features. Beyond the disease features and associated conditions (eg, uveitis and inflammatory bowel disease), comorbidities play an important role in selecting therapy for an individual patient. METHODS: We performed a systematic literature review. We examined the available evidence to inform treatment selection based on the presence or absence of comorbidities in psoriatic arthritis (PsA). RESULTS: Common comorbidities in PsA that may affect treatment selection include presence of baseline cardiovascular disease (CVD) or high risk for CVD, obesity and metabolic syndrome, liver disease, mood disorders, including depression in particular, chronic infections, malignancies, osteoporosis, and fibromyalgia and/or central sensitization. CONCLUSION: Comorbidities may influence both the effectiveness of a given therapy but also the potential for adverse events. It is important to assess for the presence of comorbidities prior to therapy selection.