INTRODUCTION:Glucocorticoids (GCs) are the mainstay treatment for acute and chronic rheumatic diseases. However, several treatment guidelines recommend limited use of GCs due to their associated toxicity. Rheumatic diseases, including rheumatoid arthritis, vasculitis, and polymyalgia rheumatica, often entail prolonged GC treatment, which may lead to major GC-related adverse events (AEs), such as osteoporosis, fracture, hyperglycemia, infection, and weight gain, along with cardiovascular, ophthalmic, and psychiatric-related AEs. AREAS COVERED:This review elaborates on common GC-associated toxicities, the requirement of baseline assessment of patients before GC initiation, and the use of steroid-sparing agents. It also indicates differences in GC-prescribing patterns between primary care physicians (PCPs) and specialists, highlighting referral delay challenges for suspected rheumatic disease cases. EXPERT OPINION:Treatment guidelines recommend baseline assessment and continuous monitoring of patients prescribed long-term GC treatment. In patients with rheumatic diseases, different risk contributing factors are responsible for GC-related AEs and are found to be dependent on dose and duration. GC therapies are an integral part of managing rheumatic diseases; however, inclusion of steroid-sparing alternative therapies could help reduce the long-term GC toxicity burden. Early referral and good communication between PCPs and specialists play an important role in reducing the long-term GC treatment burden.

This study aimed to evaluate a subsequent treatment response among patients with rheumatoid arthritis (RA) who initiated and remained on a first-line tumor necrosis factor inhibitor (TNFi) after achieving or not achieving an initial response. This real-world, retrospective cohort study included patients with RA in moderate/high disease activity (MDA/HDA), defined by Clinical Disease Activity Index (CDAI) score > 10, who initiated a first-line TNFi and remained on therapy for ≥ 12 months. Data were analyzed according to the time of initial evaluation: 3 months (N = 1215) or 6 months (N = 1318). Primary outcome: proportion of patients achieving low disease activity (LDA)/remission in CDAI (≤ 10) at the initial evaluation; secondary outcome: proportion of patients achieving minimal clinically important difference (MCID) in CDAI. Patients were categorized as responders or nonresponders according to outcome achievement, then analyzed for subsequent response at 12 months and maintenance of initial response through 12 months. After 3 months, 65.9

Evaluate patterns of stringent disease control with 2 years of guselkumab across key disease-identified domains and patient-reported outcomes (PROs) in subgroups of patients with psoriatic arthritis (PsA) defined by baseline characteristics. This post hoc analysis of DISCOVER-2 (Clinicaltrials.gov NCT03158285) evaluated biologic-naïve PsA patients (≥ 5 swollen/ ≥ 5 tender joints, C-reactive protein [CRP] ≥ 0.6 mg/dL) randomized to guselkumab every 4 weeks (Q4W); guselkumab at Weeks 0 and 4, then Q8W; or placebo with crossover to guselkumab Q4W at Week 24. Achievement of American College of Rheumatology 50/70

ObjectiveTo report 5-year efficacy and safety of upadacitinib (UPA) in rheumatoid arthritis (RA) from the phase III long-term extension (LTE) of SELECT-NEXT.MethodsPatients on stable conventional synthetic disease-modifying antirheumatic drugs were randomized to UPA 15 mg once daily (QD), UPA 30 mg QD, or placebo for 12 weeks. Following this, placebo-randomized patients were switched to UPA 15 mg QD or UPA 30 mg QD in the LTE; UPA-randomized patients continued their original dose. Blinding remained until dose switching from UPA 30 mg QD to UPA 15 mg QD because of approval of UPA 15 mg QD; the earliest switch occurred at week 168. Efficacy (as observed) and treatment-emergent adverse events (TEAEs) are reported through 5 years.ResultsOverall, 611 (92%) randomized patients entered the LTE; 271 (44%) discontinued the study drug by 5 years, primarily because of adverse events (16%). Clinical outcomes improved or were maintained at 5 years; 51% and 43% of patients achieved Clinical Disease Activity Index remission and 75% and 66% achieved Disease Activity Score in 28 joints based on C-reactive protein < 2.6 among those initially randomized to UPA 15 mg QD and UPA 30 mg QD, respectively. Proportions of patients achieving ≥ 20%/50%/70% improvement in American College of Rheumatology criteria responses increased from week 60 through 5 years. Results were similar regardless of initial randomization to UPA or placebo. TEAEs, including TEAEs of special interest, were consistent with earlier analyses and other SELECT studies. Malignancies (excluding nonmelanoma skin cancer), major adverse cardiovascular events, and venous thromboembolic events were reported infrequently. No new safety signals were observed.ConclusionThe 5-year benefit-risk profile for UPA in RA remains favorable. (SELECT-NEXT; ClinicalTrials.gov:NCT02675426)

Objective Evaluate patient‐reported outcomes after 6 months of on‐label guselkumab use in patients with rheumatologist‐diagnosed active psoriatic arthritis (PsA) enrolled in the CorEvitas PsA/Spondyloarthritis Registry. Methods This analysis includes registry participants who initiated and persisted with on‐label guselkumab (after US Food and Drug Administration approval for PsA; 100 mg at weeks 0, 4, and every 8 weeks) at their 6‐month follow‐up visit (On‐Label Persisters). Among patients not meeting response criteria at baseline, responses at 6 months were determined for patient‐reported outcomes, including patient‐reported pain (0–100 mm visual analog scale), patient global assessment of arthritis + psoriasis (PtGA; 0–100 visual analog scale), and Health Assessment Questionnaire‐Disability Index (HAQ‐DI; 0‐3). Unadjusted, nominal P values were calculated via single‐proportion, one‐sided test (H0 = 0%; α = 0.05). Results Of 90 On‐Label Persisters, most had treatment‐resistant PsA (92.2% and 73.3% previously received ≥1 and ≥2 biologic/targeted synthetic disease‐modifying antirheumatic drugs, respectively), with mean (SD) baseline patient‐reported pain, PtGA, and HAQ‐DI scores of 57.0 (24.6), 50.3 (24.4), and 0.9 (0.6), respectively. Among those with patient‐reported pain and PtGA scores of at least 15 at baseline, 40.2% (33/82) and 46.8% (36/77), respectively, achieved at least 15‐mm reductions at 6 months; among those with HAQ‐DI scores of at least 0.35 and more than 0.5 at baseline, respectively, 30.4% (21/69) achieved improvements of at least 0.35 and 10.3% (6/58) achieved scores of 0.5 or lower at 6 months (all nominal P < 0.001). Conclusion Pain and physical function are important contributors to health‐related quality of life. In this real‐world population of patients with treatment‐resistant PsA and 6 months of persistent guselkumab treatment, clinically meaningful improvements in pain and physical function were achieved by approximately 40% and 30% of patients, respectively.

Background Guselkumab (GUS) is associated with robust and sustained improvement in psoriatic arthritis (PsA) signs and symptoms in subgroups of patients (pts) pooled from the phase 3 DISCOVER-1 and DISCOVER-2 trials, across a variety of baseline (BL) pt characteristics through 1[1], and 2 years (DISCOVER-2 only)[2]. Objectives This post-hoc analysis using DISCOVER-2 data aimed to evaluate the efficacy of GUS in inducing long-term (Week [W]100) stringent disease control in Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)-recommended domains across BL characteristics. Methods DISCOVER-2 enrolled biologic-naïve adults with active PsA defined as ≥5 swollen and ≥5 tender joint counts (SJC; TJC) and C-reactive protein (CRP) ≥0.6 mg/dL. 739 pts were randomized (1:1:1) and treated with GUS 100 mg every 4 weeks (Q4W; n=245); GUS 100 mg at Week 0, Week 4, then every 8 weeks (Q8W; n=248); or placebo (n=246) with crossover to GUS 100 mg Q4W at W24. In this analysis, only GUS-randomized pts were included (n=493). Achievement of the following outcomes at W100 was assessed: minimal disease activity (MDA), American College of Rheumatology 50% improvement (ACR50), ACR70, Investigator's Global Assessment score of 0 (clear skin) (IGA 0), Psoriatic Arthritis Disease Activity Score – low disease activity (PASDAS LDA), resolution of enthesitis and dactylitis, Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) response (≥4-point improvement), and Health Assessment Quality Disease Index (HAQ-DI) response (≥0.35-point improvement). BL characteristics of interest were pt sex, baseline body mass index (BMI), SJC, TJC, PsA duration, CRP, % body surface area (BSA) with psoriasis, and PASI score, and use of conventional synthetic (cs) DMARDs and methotrexate (MTX). Non-responder imputation was used for missing categorical response data. Results 442 (90%) GUS-randomized pts completed study treatment through W100. With few exceptions, achievement of MDA response (Figure 1) at Week 100 was demonstrated across a variety of baseline pt characteristics, without consistent differences in proportion of responders across pt subgroups of adequate sample size or between GUS dosing regimens. Similar trends were observed for achievement of ACR50, ACR70, IGA 0, PASDAS LDA, enthesitis resolution, dactylitis resolution, FACIT-F response, and HAQ-DI response. Conclusion Irrespective of dosing regimen, treatment with GUS resulted in sustained achievement of several stringent endpoints spanning key GRAPPA-recommended domains through 2 years across a variety of BL demographic and disease characteristics. These results further support the long-term efficacy of GUS across the full spectrum of PsA disease domains and diverse PsA populations. References [1]Ritchlin CT. et al. RMD Open. 2022 Mar;8(1):e002195; [2]Ritchlin CT. et al. Abstract N°AB0526. EULAR 2021. Acknowledgements: NIL. Disclosure of Interests Christopher T. Ritchlin Consultant of: AbbVie, Amgen, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, and UCB, Philip J Mease Speakers bureau: AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Consultant of: AbbVie, Aclaris, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Inmagene, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Wolf-Henning Boehncke Consultant of: AbbVie, Almirall, Eli Lilly, Janssen, Leo, Novartis, and UCB, John Tesser Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Janssen and Pfizer, Consultant of: AbbVie, Eli Lilly, Janssen, Novartis, and Pfizer, advisory board fees from Bristol Myers Squibb, Eli Lilly, Gilead, Janssen, Novartis, and Pfizer, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Celgene, CorEvitas, Eli Lilly, Gilead, Janssen, Pfizer, and Sun Pharma, Soumya D Chakravarty Employee of: Janssen Scientific Affairs, LLC; shareholder in Johnson & Johnson, of which Janssen Scientific Affairs, LLC is a wholly-owned subsidiary, Emmanouil Rampakakis Consultant of: Janssen, Employee of: JSS Medical Research, May Shawi Employee of: Janssen Pharmaceutical Companies of Johnson & Johnson; shareholder of Johnson & Johnson, Elena Schiopu Consultant of: Janssen, Grant/research support from: Janssen, Joseph F. Merola Consultant of: AbbVie, Arena, Biogen, Bristol Myers Squibb, Dermavant, Eli Lilly, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Iain McInnes Shareholder of: Causeway Therapeutics, and Evelo Compugen; Non Exec Roles: NHS GGC Board Member, Evelo Board of Directors and Versus Arthritis Trustee Status, Consultant of: AbbVie, Amgen, Astra Zeneca, Bristol Myers Squibb, Cabaletta, Compugen, Eli Lilly, Gilead, GSK, Janssen, Novartis, Pfizer, Roche, Sanofi, and UCB, Grant/research support from: Astra Zeneca, Amgen, Bristol Myers Squibb, Eli Lilly, GSK, Janssen, Novartis, Roche, and UCB, Atul Deodhar Speakers bureau: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Aurinia, Bristol Myers Squibb, Celgene, Eli Lilly, GSK, Janssen, MoonLake, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Eli Lilly, GSK, Novartis, Pfizer, and UCB.

Abstract Background This study sought to evaluate the efficacy and safety of tofacitinib in patients with rheumatoid arthritis with distinct treatment histories. Methods Pooled phase II/III trial data from patients who received tofacitinib 5 or 10 mg twice daily or placebo, as monotherapy or with conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs), were analyzed post hoc. Separate evaluations were conducted for populations with a prior inadequate response (IR) to: 1) non-methotrexate (MTX) csDMARDs only (non-MTX csDMARD-IR; n = 537); 2) MTX (MTX-IR; n = 3113); and 3) biologic (b)DMARDs (bDMARD-IR; n = 782). Efficacy outcomes included rates of response (American College of Rheumatology 20/50/70% response criteria) and remission (Disease Activity Score in 28 joints derived from 4 measures, erythrocyte sedimentation rate [DAS28-4(ESR)] < 2.6) at month 3, and changes from baseline in DAS28-4(ESR) and Health Assessment Questionnaire–Disability Index scores. Safety was assessed up to month 24. Results At month 3, efficacy was generally improved with tofacitinib (both doses) vs placebo in each population. Generally, efficacy outcomes with tofacitinib were numerically more favorable in non-MTX csDMARD-IR vs MTX-IR or bDMARD-IR patients. Over 24 months, crude incidence rates for adverse events (AEs), serious AEs, and discontinuations due to AEs were generally numerically lower in non-MTX csDMARD-IR and MTX-IR vs bDMARD-IR populations; rates for AEs of special interest were generally similar across populations. Conclusions Tofacitinib provided clinical benefit across patients with rheumatoid arthritis with a range of prior treatment experience but may have greater efficacy and an improved benefit/risk profile in those with fewer prior treatments. Trial registration NCT00147498/NCT00413660/NCT00550446/NCT00603512/NCT00687193/NCT00976599/NCT01359150/NCT00847613/NCT00814307/NCT00853385/NCT00960440/NCT01039688/NCT00856544.

OBJECTIVE:Preliminary evidence suggests that vagus nerve stimulation (VNS) may have some benefit in patients with rheumatoid arthritis (RA); however, prior studies have been small and/or uncontrolled; this study aimed to address that gap.METHODS:This randomized, double-blind, sham-controlled trial enrolled patients aged 18 to 75 years with active RA who had failed conventional synthetic disease-modifying antirheumatic drugs (DMARDs) and were naïve to biologic and/or targeted synthetic DMARDs. All patients received an auricular vagus nerve stimulator and were randomized 1:1 to active stimulation or sham. The primary endpoint was the proportion of patients achieving 20% improvement in American College of Rheumatology criteria (ACR20) at week 12. Secondary endpoints included mean changes in disease activity score of 28 joints with C-reactive protein (DAS28-CRP) and Health Assessment Questionnaire-Disability Index (HAQ-DI).RESULTS:A total of 113 patients (mean age 54 years; 82% female) enrolled, and 101 patients (89.4%) completed week 12. ACR20 response at week 12 was 25.0% for active stimulation versus 26.9% for sham (difference vs. sham, -1.9; 95% CI, -18.8, 14.9, P = 0.823). The least square mean ± SE change in DAS28-CRP was -0.95 ± 0.16 for active stimulation and -0.66 ± 0.16 for sham (P = 0.201); in HAQ-DI it was -0.19 ± 0.06 for active stimulation and -0.02 ± 0.06 for sham (P = 0.044). Adverse events occurred in 17 patients (15%); all were mild or moderate.CONCLUSION:Auricular VNS did not meaningfully improve RA disease activity. If VNS with other modalities is pursued in the future for the treatment of RA, larger, controlled studies will be needed to understand its utility.

OBJECTIVE:To assess 12-month safety and efficacy of pegloticase + methotrexate (MTX) versus pegloticase + placebo (PBO) cotherapy in a PBO-controlled, double-blind trial (A randomized, double-blind, placebo-controlled, multicenter, efficacy and safety study of methotrexate to increase response rates in patients with uncontrolled gout receiving pegloticase [MIRROR RCT]).METHODS:Patients with uncontrolled gout (serum urate level [SU] ≥7 mg/dl, oral urate-lowering therapy failure or intolerance, and presence of one or more gout symptoms [one or more tophi, two or more flares in 12 months, gouty arthropathy]) were randomized 2:1 to receive pegloticase (8-mg infusion every 2 weeks) with blinded MTX (oral 15 mg/week) or PBO for 52 weeks. Efficacy end points included proportion of responders (SU level <6 mg/dl for ≥80% of examined month) in the intent-to-treat population (ITT) (all randomized patients) during month 6 (primary end point), month 9, and month 12; proportion with resolution of one or more tophi (ITT); mean SU reduction (ITT); and time to SU-monitoring pegloticase discontinuation. Safety was evaluated via adverse event reporting and laboratory values.RESULTS:Month 12 response rate was significantly higher in patients cotreated with MTX (60.0% [60 of 100] vs. 30.8% [16 of 52]; difference: 29.1% [95% confidence interval (CI): 13.2%-44.9%], P = 0.0003), with fewer SU discontinuations (22.9% [22 of 96] vs. 63.3% [31 of 49]). Complete resolution of one or more tophi occurred in 53.8% (28 of 52) versus 31.0% (9 of 29) of MTX versus PBO patients at week 52 (difference: 22.8% [95% CI: 1.2%-44.4%], P = 0.048), more than at week 24 (34.6% [18 of 52] vs. 13.8% [4 of 29]). Consistent with observations through month 6, pharmacokinetic and immunogenicity findings showed increased exposure and lower immunogenicity of pegloticase when administered with MTX, with an otherwise similar safety profile. No infusion reactions occurred after 24 weeks.CONCLUSION:Twelve-month MIRROR RCT data further support MTX cotherapy with pegloticase. Tophi resolution continued to increase through week 52, suggesting continued therapeutic benefit beyond month 6 for a favorable treatment effect.

The aim of this work is to evaluate treatment persistence and clinical outcomes after 6 months of on-label guselkumab use in patients with rheumatologist-diagnosed active psoriatic arthritis (PsA) enrolled in the CorEvitas PsA/Spondyloarthritis Registry. Participants with PsA who initiated and persisted with on-label guselkumab use post-Food and Drug Administration (FDA) approval for active PsA (7/13/2020; subcutaneous 100 mg at weeks 0, 4, and every 8 weeks) at their 6-month follow-up visit (occurring through 3/31/2023) comprised the primary analysis population (On-Label Persisters). Hierarchical, multiplicity-controlled primary and secondary outcomes were mean (95

Infliximab and golimumab are intravenously (IV) administered tumor necrosis factor inhibitors approved to treat moderate-to-severe rheumatoid arthritis (RA) with concomitant methotrexate. Owing to differences in biologic construct, patients with IV-infliximab treatment failure may benefit from switching to IV-golimumab. Utilizing the ACR’s Rheumatology Informatics System for Effectiveness (RISE), a large electronic health records registry based in the USA, we assessed RA disease activity in patients switching from IV-infliximab to IV-golimumab. This retrospective, longitudinal, single-arm study included adults (≥ 18 years) with ≥ 1 RA diagnosis code between 2014 and 2018 and ≥ 1 IV-infliximab prescription within 6 months of a new IV-golimumab order (index date). Longitudinal assessments of disease activity using the Clinical Disease Activity Index (CDAI) were calculated in patients continuing IV-golimumab for 6–9- and 9–12-months post-switch. Paired t-tests evaluated significance of mean improvements during the follow-up periods. Most RA patients with disease activity assessments during the 6-month follow-up (N = 100; mean age: 65.3 years; 81% female; 74% white) demonstrated moderate-to-high disease activity (CDAI: 73% [38/52]) at enrollment. On average, patients showed significant improvement in disease activity within 6–9 months of switching; mean CDAI scores improved from 21.3 to 14.1 (p < 0.0001) and were durable through 9–12 months of treatment. Real-world patients with moderate-to-high disease activity who switched from IV-infliximab to IV-golimumab demonstrated significant and sustained improvements post-switch as measured by the CDAI.