Rheumatology and Therapy最新文献

Introduction: Evidence is limited on the clinical and economic burden of eosinophilic granulomatosis with polyangiitis (EGPA) in Europe. We evaluated EGPA healthcare resource utilisation (HCRU), days off work, and costs in Germany.

Methods: This analysis used claims data from the German statutory health insurance fund AOK Plus. Patients with newly diagnosed EGPA (index date 2016-2020; ≥ 12 months pre-diagnosis health plan enrolment) were matched (1:4) with general insured individuals without EGPA. Baseline was 12 months pre-diagnosis; follow-up was until 31 December 2020, insurance disenrollment, or death. Outcomes included HCRU and related costs and days off work.

Results: The study included 155 patients and 620 matched individuals. In the EGPA cohort, all-cause HCRU was higher post-diagnosis than during baseline in all categories. Mean annualised in-patient hospitalisations/patient and pharmacy claims/patient for any EGPA therapy were 2.99 and 5.87, respectively, during 1-year post-diagnosis versus 1.15 and 1.80, respectively, during baseline. Mean total annualised cost of all-cause HCRU/patient with EGPA was €19,700 during 1-year post-diagnosis versus €6,678 during baseline, with in-patient hospitalisations and pharmacy costs the main cost drivers of EGPA care. Over 5 years post-diagnosis, mean annualised HCRU rate per patient was significantly higher for the EGPA versus the matched cohort for all evaluated aspects of HCRU (p < 0.001). The mean total annualised all-cause HCRU cost was sevenfold higher (EGPA €14,771/patient vs matched cohort €2,094/patient; p < 0.001). In-patient hospitalisation (€8,276/patient) was the single largest driver of all-cause costs over 5 years post-diagnosis. Mean total days off work and associated annualised costs of productivity loss were also significantly higher over 5 years post-diagnosis in the EGPA versus the matched cohort (30.74 vs 13.35 days/year; €3,632 vs €1,555 annually/patient, both p < 0.001).

Conclusions: These real-world data highlight the substantial economic burden associated with EGPA, characterised by increased HCRU, costs and productivity losses, underscoring the need for effective management strategies.

Introduction: This work aims to describe the risk of major adverse cardiovascular events (MACE), malignancy, and mortality in real-world patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), or axial spondyloarthritis (axSpA) treated with subcutaneous (SC) golimumab.

Methods: This post hoc analysis included patients treated with SC golimumab from the BioTRAC registry. Incidence rates (IR) per 100 patient-years (PYs) and time to onset of adverse events of special interest (AEoSI), including MACE, malignancies, mortality, serious AEs (SAEs), and serious infections (SIs), were assessed in subgroups based on age, sex, prior tumor necrosis factor inhibitor experience, smoking status, and baseline methotrexate and oral steroid use. All analyses were stratified by indication.

Results: Of 1231 patients included, 529 had RA, 281 had PsA, and 421 had axSpA. At baseline, mean patient age was 57.7, 52.8, and 45.7 years in the RA, PsA, and axSpA groups, respectively. Most patients with RA (76.2%) and PsA (53.7%); 40.9% of patients with axSpA were female. The IR (95% confidence interval) for MACE was 1.1 (0.6, 2.0) events/100 PYs in the RA group with no events in the PsA and axSpA groups. Malignancy IRs were 1.4 (0.8, 2.3), 0.4 (0.0, 1.3), and 1.0 (0.4, 2.1)/100 PYs. SAE incidence ranged from 7.6 (5.5, 10.3)/100 PYs in the PsA group to 11.4 (9.4, 13.6) in the RA group, and that of SIs from 1.3 (0.5, 2.7)/100 PYs in patients with PsA to 2.3 (1.4, 3.4) in patients with RA. IRs for mortality were 0.7 (0.3, 1.4; n = 7), 0.2 (0.0, 1.0; n = 1), and 0.3 (0.0, 1.1; n = 2)/100 PYs in RA, PsA, and axSpA, respectively. Older patients with RA had a significantly shorter time to MACE (p = 0.007).

Conclusions: Patients with RA, PsA, and axSpA treated with SC golimumab in the real world had a low incidence of MACE, malignancy, and all-cause mortality, further confirming the safety of golimumab for the treatment of rheumatic diseases.

Trial registration number and date: ClinicalTrials.gov identifier, NCT00741793, August 22, 2008.

Introduction: Sjögren's disease (SjD) is often characterized by the presence of anti-SSA/Ro and anti-SSB/La autoantibodies. The Clinical European Alliance of Associations for Rheumatology (EULAR) Sjögren's Syndrome Disease Activity Index (ClinESSDAI) and Patient-Reported Index (ESSPRI) assess disease activity and patient-reported symptomatology; however, their association with patient-reported outcome measures (PROMs) remains unclear. We aimed to describe systemic disease activity in seropositive and seronegative SjD patients and evaluate the association between proxy ClinESSDAI and ESSPRI scores with PROMs.

Methods: Data were drawn from the Adelphi Real World SjD Disease Specific Programme™, a cross-sectional survey conducted in France, Germany, Italy, Spain and the United States between June and October 2018. Physicians reported patient demographics and clinical characteristics. Patients completed the EQ-5D-3L and Visual Analogue Scale (EQ-VAS), and the Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F). Proxy ClinESSDAI and ESSPRI scores were calculated using physician-reported organ activity and averaged patient ratings of dryness, pain, and fatigue, respectively. Associations between ClinESSDAI, ESSPRI, physician-reported disease severity, and PROMs were determined using linear and logistic regression modeling. Statistical significance was p < 0.05 for all tests.

Results: Overall, 319 rheumatologists provided data on 1879 patients with SjD. Mean (standard deviation) patient age was 53.2 (12.2) years, 89% were female, and 89% were White. Of patients who received serum antibody testing for both anti-SSA/Ro and anti-SSB/La antibodies (n = 1344), 69% were double seropositive and 6% were double seronegative. The most common symptoms experienced by double seropositive and double seronegative SjD patients, respectively, included dry eyes (94% and 74%), and physical fatigue (82% and 60%). ClinESSDAI and ESSPRI were significantly associated with EQ-5D-3L, EQ-VAS, and FACIT-F (all p < 0.001).

Conclusions: Systemic disease activity and patient-reported symptomatology were significantly associated with health-related quality of life measures, highlighting the need for disease management that considers both clinical outcomes and the patient experience.

Introduction: The aim of this study was to evaluate guselkumab efficacy through week 100 in participants with psoriatic arthritis (PsA) and severe disease activity or patient global assessment (PtGA).

Methods: This post hoc analysis utilized DISCOVER-2 (NCT03158285) data from 739 biologic-naïve adults with active PsA (≥ 5 swollen/tender joints, C-reactive protein  ≥ 0.6 mg/dL) randomized to guselkumab every 4 weeks (Q4W) or at weeks 0 and 4, then every 8 weeks (Q8W); or placebo with crossover to guselkumab Q4W at week 24. Severe disease activity was defined as clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA) > 27, Psoriatic Arthritis Disease Activity Score (PASDAS) ≥ 5.4, and PtGA Arthritis + Psoriasis ≥ 80 mm. Least squares mean (LSM) changes in cDAPSA, PASDAS, and PtGA were estimated with mixed models for repeated measures adjusted for baseline factors.

Results: Baseline characteristics among 648 (88%), 639 (86%), and 218 (29%) participants meeting the cDAPSA, PASDAS, and PtGA criteria for severe disease activity, respectively, were generally balanced across cohorts. LSM improvements from baseline with guselkumab Q4W/Q8W vs. placebo were -5.9 (p = 0.3905)/-7.2 (p = 0.0379) for cDAPSA at week 2; -1.5/-1.5 for PASDAS (both p < 0.0001); and -30.0/-32.1 for PtGA at week 8 (both p < 0.01). Differences vs. placebo increased through week 24 in the respective cohorts with guselkumab Q4W/Q8W: -9.8/-9.0, -1.1/-1.1, -24.0/-20.2 (all p < 0.0001). Through week 100 of guselkumab Q4W/Q8W treatment, LSM improvements of 69/74%, 52/54%, and 64/63% from baseline in cDAPSA (-35.9/-35.6), PASDAS (-3.6/-3.7), and PtGA (-56.8, -55.5), respectively, were observed. Regardless of severe disease activity definition, approximately 80% of guselkumab-randomized participants who achieved low disease activity at week 24 maintained this response at week 100.

Conclusion: In biologic-naïve participants with PsA and severe disease activity, guselkumab demonstrated early and durable clinically meaningful improvements in key PsA domains through 2 years.

Trial registration: ClinicalTrials.gov, NCT03158285.

Introduction: The journey to axial spondyloarthritis (axSpA) diagnosis is often prolonged, and delayed diagnosis has been associated with poorer outcomes and increased healthcare costs. This study aimed to characterize the patient diagnostic journey in axSpA and associated healthcare resource utilization (HCRU) and costs in the US.

Methods: This observational, retrospective US MarketScan^® study utilized insurance claims data from the Commercial/Medicare Supplemental (January 2008-March 2023) and Medicaid (January 2008-December 2022) databases to assess the time to diagnosis in adult patients with back pain onset prior to a new axSpA diagnosis. This study evaluated the time to axSpA diagnosis from the earliest back pain diagnosis, and the diagnostic journey through the number of consultations with healthcare professionals (HCPs) for back pain, diagnostic tests, and imaging procedures. Back pain-related HCRU and costs were assessed, as well as pharmacy claims during this period.

Results: Of 97,469 patients included, 29.0% experienced time to diagnosis of ≥ 6 years, with a mean (standard deviation) of 4.5 (2.8) years to diagnosis. Prior to axSpA diagnosis, patients saw an average of 4.57 HCPs annually and had 20.7 back pain-related visits overall for back pain-related causes. Between the earliest back pain diagnosis and axSpA diagnosis, 55.9% of patients experienced > 10 back pain consultations, and patients underwent a range of diagnostic tests and imaging procedures. The median sum of non-capitated back pain-related costs up to axSpA diagnosis was $883.19 per patient per year, plus $1127.57 per patient per year for pharmacy prescriptions.

Conclusions: This study shows that diagnostic delay is a challenge for patients with axSpA in the US, despite numerous back pain consultations, specialist visits, and diagnostic tests. These findings highlight the urgent need for strategies to enhance recognition of axSpA and improve the patient diagnostic journey.

Connective tissue disease-related interstitial lung disease (CTD-ILD) refers to a range of pulmonary complications arising from connective tissue disorders, characterized by alveolar inflammation and interstitial fibrosis. Various factors, such as the specific type of connective tissue disease, infections, and hypoxemia, influence acute exacerbations of CTD-ILD. Treatment strategies typically include targeted interventions for precipitating factors, glucocorticoids, immunosuppressants, and supportive care. Glucocorticoids play a key role in managing acute exacerbations of CTD-ILD; however, the optimal dosing and duration of treatment remain uncertain. Immunosuppressants show potential therapeutic value, but further studies are needed to determine the most effective regimens for CTD-ILD patients. Supportive care, including respiratory support and oxygen therapy, is crucial for symptom relief and correction of hypoxia. Despite recent treatment advancements in China, significant challenges remain in optimizing outcomes and improving survival rates in CTD-ILD, highlighting the need for a comprehensive, individualized management approach for Chinese patients. Future research should focus on elucidating the pathogenesis of CTD-ILD, tailoring treatment strategies, and establishing standardized diagnostic and management protocols based on the Chinese population.

Introduction: Muscle and skin involvement are well defined in dermatomyositis but other symptoms contribute significantly to the disease burden and their treatment is not well characterized. This post hoc analysis of ProDERM assessed the effect of intravenous immunoglobulin (IVIg) treatment on other manifestations of dermatomyositis beyond muscular and cutaneous involvement.

Methods: ProDERM was a randomized, placebo-controlled study. For weeks 0-16, patients with dermatomyositis received 2.0 g/kg IVIg (Octagam, 10%) or placebo every 4 weeks. Eligible patients entered the open-label extension, where all received IVIg to week 40. Pulmonary, skeletal, constitutional, gastrointestinal, and cardiovascular disease activity was assessed using the myositis disease activity assessment tool, comprising a visual analog scale (VAS; 0-10 cm) and myositis intention-to-treat activity index.

Results: Of 95 patients enrolled, 47 received IVIg and 48 received placebo to week 16. At baseline, 37.9% of patients experienced pulmonary, 64.2% experienced skeletal, 76.8% experienced constitutional, 33.7% experienced gastrointestinal, and 15.8% experienced cardiovascular involvement (VAS > 0.5). Among these patients, for those on IVIg, the following mean VAS scores decreased from baseline to week 16: pulmonary (37.7%; P = 0.001), skeletal (52.6%; P < 0.001), constitutional (44.4%; P < 0.001), and gastrointestinal (49.2%; P = 0.005). No corresponding improvement was seen with placebo except for constitutional VAS. With IVIg, the proportions of patients with arthritis (36.2 to 17.8%; P = 0.01), arthralgia (68.1 to 0.0%; P < 0.001), and fatigue (68.1 to 3.3%; P = 0.008) decreased from baseline to week 16. In the combined cohort, the proportions of patients with dysphonia (20.0 to 8.1%; P = 0.04), arthralgia (66.3 to 39.8%; P < 0.001), weight loss (10.5 to 3.4%; P = 0.04), fatigue (75.8 to 50.0%; P < 0.001), and dysphagia (40.0 to 18.4%; P < 0.001) decreased from baseline to week 40.

Conclusion: IVIg was effective in treating pulmonary, skeletal, constitutional, and gastrointestinal manifestations of dermatomyositis. We advocate exploring IVIg as treatment for dermatomyositis, beyond muscle and skin manifestations.

Trial registration: ClinicalTrials. gov identifier, NCT02728752.

Objectives: Our objective was to evaluate the comparative effects of five Janus kinase inhibitors (JAKis) with ten interventions, comparing their impact on major adverse cardiovascular events (MACE) and thromboembolism events (TE) in patients with psoriatic arthritis (PsA) through network meta-analysis (NMA).

Methods: We conducted a search across four databases from inception to September 30, 2024. We also included studies comparing JAKis with placebo or TNFi in adults (≥ 18 years) with PsA. The primary outcomes were the incidence of MACE and TE. We used network meta-analysis with random effects to estimate summary risk ratios (RRs).

Results: Eleven studies met the eligibility criteria. Combined RCT and LTE data showed 23 MACE and 26 TE events, with incidence rates (IR) of 0.25 and 0.29 per 100 person-years for MACE and TE, respectively. Across all RCT data, there were 12 MACE and 8 TE events, with IRs of 0.62 and 0.41 per 100 person-years for MACE and TE, respectively. In eligible RCTs, tofacitinib (5 mg and 10 mg) and upadacitinib (30 mg) were associated with a lower risk of TE compared to placebo (GRADE certainty: moderate, moderate, and high, respectively). Compared to adalimumab, upadacitinib (15 mg and 30 mg) was associated with a decreased risk of MACE in RCT/LTE data (GRADE certainty: moderate and moderate, respectively).

Conclusions: Tofacitinib and upadacitinib are superior to placebo and comparable to adalimumab regarding MACE and TE risk, even with long-term exposure, which may be positively considered in PsA treatment. The cardiovascular safety of new investigational JAKis needs further validation.

Introduction: This study aimed to evaluate the influence of background conventional synthetic disease-modifying antirheumatic drug (csDMARD) use on efficacy and safety of deucravacitinib, a first-in-class, oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor, in patients with psoriatic arthritis (PsA).

Methods: This phase 2, double-blind trial randomized 203 patients with active PsA 1:1:1 to oral placebo, deucravacitinib 6 mg, or deucravacitinib 12 mg once daily for 16 weeks. Patients had failed or were intolerant to ≥ 1 non-steroidal anti-inflammatory drug (NSAID), glucocorticoid, csDMARD and/or one tumour necrosis factor inhibitor. Patients were not stratified by csDMARD use and were allowed one background csDMARD if used for ≥ 3 months with stable dose for > 28 days prior to day 1; patients could not initiate new csDMARD treatment. This post hoc analysis evaluated the influence of background csDMARD use on efficacy outcomes, which included American College of Rheumatology (ACR) 20 responses and ACR scoring components; Psoriasis Area and Severity Index (PASI) scores; Psoriatic Arthritis Disease Activity Scores (PASDAS); and on safety measures.

Results: Baseline clinical characteristics and disease activity were generally similar among subgroups regardless of csDMARD use. At baseline, 65.0% of patients were taking background csDMARDs and among these 84.1% were taking methotrexate; percentages of methotrexate use were similar across groups. Similar ACR 20 response rates at week 16 were observed with deucravacitinib treatment in patients with vs without baseline csDMARD use compared with placebo (deucravacitinib 6 mg: 57.8% vs 44.0%; deucravacitinib 12 mg: 62.8% vs 62.5%; and placebo: 31.8% vs 31.8%, respectively). Similar responses with deucravacitinib compared with placebo, regardless of background csDMARD use, were observed in individual ACR components, PASI score, and PASDAS. The safety profile of deucravacitinib treatment was similar in patients with and without csDMARD use.

Conclusion: Background csDMARD use did not affect the efficacy or safety of deucravacitinib in this phase 2 PsA study. Graphical Abstract available for this article.

Trial registration: ClinicalTrials.gov ( https://clinicaltrials.gov ): NCT03881059.

Introduction: This guideline offers evidence-based recommendations for physicians and policymakers on managing axial spondyloarthritis (axSpA) in Saudi Arabia.

Methods: A panel of 14 experts in research methodology, rheumatology, family medicine, and clinical pharmacology in Saudi Arabia approved 45 questions related to the monitoring and treatment, pharmacological and non-pharmacological, of different subtypes of axSpA. We conducted a search of different databases, including PubMed, EMBASE, and the Cochrane Library, from 2010 to 2024 to identify systematic reviews, meta-analyses, and clinical studies related to the diagnosis and management of axSpA. To evaluate the certainty of the evidence and formulate recommendations, we employed the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. The expert panel voted electronically on each recommendation. A recommendation was finalized when over 70% of the voting panel agreed.

Results: We issued 31 evidence-based recommendations and seven statements based on the experts' opinions, which are grouped into nine categories. This guideline recommends initiating non-steroidal anti-inflammatory drugs (NSAIDs) as the first-line therapy for patients with symptomatic axSpA. If NSAIDs are ineffective, second-line treatments such as tumor necrosis factor inhibitors (TNFis), interleukin-17 inhibitors (IL-17is), or Janus kinase inhibitors (JAKis) should be considered. Localized glucocorticoid injections are suggested as supplementary therapy for cases of isolated sacroiliitis, enthesitis, or peripheral monoarthritis not responding adequately to the treatment options.

Conclusion: The Saudi clinical practice guidelines provide updated evidence-based recommendations for monitoring and treating adults with axSpA. These recommendations help guide the best practice for healthcare professionals in managing patients with axSpA in Saudi Arabia.