Rheumatology and Therapy最新文献

Introduction: Glucocorticoids are commonly used to treat immunoglobulin G4-related disease (IgG4-RD), but there is limited real-world evidence describing glucocorticoid-related toxicities in this population. This study assessed glucocorticoid use and toxicities during the first year after diagnosis among patients with IgG4-RD.

Methods: The IQVIA PharMetrics® Plus database was used to identify adults with IgG4-RD using a validated algorithm. Patients were stratified according to glucocorticoid use during the 12-month study period following the first observed IgG4-RD-related diagnosis (index date): low glucocorticoid use (prednisone equivalent daily dose [PEDD] < 5 mg/day) or high glucocorticoid use (PEDD ≥ 5 mg/day). Incident glucocorticoid-related toxicities were assessed during the study period and incidence was compared between groups using Chi-square tests.

Results: Among 295 patients with IgG4-RD, 150 (50.8%) had low glucocorticoid use, and 145 (49.2%) had high glucocorticoid use during the study period. In each glucocorticoid group, mean PEDD was highest in the 3 months post-index and subsequently decreased. At 12 months post-index, 24.7% of the low glucocorticoid use group and 60.7% of the high glucocorticoid use group were receiving glucocorticoids. The high glucocorticoid use group had a significantly higher mean (± standard deviation) number of incident glucocorticoid-related toxicities (1.8 ± 1.7 vs. 1.2 ± 1.3) and more frequently had ≥ 3 glucocorticoid-related toxicities (29.0% vs. 13.3%; both p < 0.01) compared to the low glucocorticoid use group. Specifically, cardiovascular- (29.0% vs. 18.7%), gastrointestinal- (29.7% vs. 16.0%), and infection-related (31.0% vs. 17.3%) toxicities were significantly more common in the high glucocorticoid use group than the low glucocorticoid use group (all p < 0.05).

Conclusions: In this retrospective, claims-based analysis, high glucocorticoid use was seen in half of patients with IgG4-RD during the first year following diagnosis. Patients with high glucocorticoid use experienced significantly more incident glucocorticoid-related toxicities than those with low use during this first year.

Introduction: Biosimilars need to demonstrate similarity in terms of quality, pharmacokinetics (PK), efficacy, safety, and immunogenicity. Here, we report the outcome of a comprehensive evaluation of the immunogenicity of the biosimilar BAT1806 compared with the tocilizumab reference product (TCZ).

Methods: We conducted a post hoc analysis of study BAT1806-001-CR, a comparative PK study in healthy male volunteers (n = 129), and BAT1806-002-CR, a phase III, 52-week trial in patients with rheumatoid arthritis (n = 621). Anti-drug antibodies (ADA), ADA titers, and neutralizing ADA were measured, and their impact on PK, safety, and efficacy parameters were assessed.

Results: In BAT1806-001-CR, treatment-induced ADA were observed in 37.8% of participants for the BAT1806 group, 28.6% for the EU-sourced TCZ group, and 31.0% for the US-sourced TCZ group, without an impact on PK and safety. In BAT1806-002-CR after 52 weeks, 28.2% of participants in the BAT1806 group developed treatment-induced ADA, compared with 24.0% in the TCZ group and 19.7% of participants who initiated TCZ and switched to BAT1806 at week 24. ADA-positive participants reported lower geometric mean serum tocilizumab trough concentrations than ADA-negative participants in all treatment groups. ADA-positive participants achieved similar efficacy outcomes to ADA-negative participants in all treatment groups. ADA were not associated with an incremental risk of treatment-emergent adverse events or hypersensitivity in any of the treatment groups.

Conclusions: The results of these post hoc analyses did not indicate any clinically relevant differences in the immunogenicity profile of intravenously administered BAT1806 compared with TCZ.

Trial registration: ClinicalTrials.gov identifiers, NCT03606876, NCT03830203.

As more lupus nephritis (LN) medications become available, identifying treatments that are disease-modifying is critical in making treatment decisions. Based on our 2022 published working definition of LN disease modification as 'minimizing disease activity with the fewest treatment-associated toxicities and slowing progression to end-stage kidney disease' (ESKD), the objective of this review was to classify current LN treatments according to the proposed kidney disease modification criteria, excluding toxicities. Based upon a selection of LN clinical trial (n = 27) and observational study (n = 20) publications, as well as the authors' clinical experiences, we evaluated the disease modification potential for 16 LN treatments (inclusive of antimalarials, glucocorticoids, immunosuppressants, calcineurin inhibitors and biologics) according to the proposed kidney disease activity and organ damage criteria at year 1, years 2-5, and > 5-year time points. Fulfilling criteria at year 1 and years 2-5 was considered evidence for disease modification potential. Satisfying criteria at > 5 years (slowing or preventing progression in SLICC/ACR Damage Index [SDI] and ESKD, and/or doubling of serum creatinine) was used to confirm disease modification. Each treatment was designated as one of the following at each time point: (a) criterion met; (b) inconclusive; (c) no available supportive data. This review excluded an assessment of potential toxicities. All LN treatments met at least one of the potential kidney disease-modification criteria at any time point, but limited relevant data in the literature meant disease modification > 5 years could only be confirmed for cyclophosphamide. Belimumab met more criteria across the three time points than any other biologic treatment but lacked > 5-year data to confirm disease modification. Further research is needed to support the classification of LN treatments as disease modifiers, particularly for > 5 years. We discuss considerations for future studies, challenges to the classification, and possible updates to published criteria.

Introduction: For patients with rheumatoid arthritis (RA) unresponsive to first-line biologic/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs), the selection of second-line b/tsDMARDs is crucial to prevent progression to difficult-to-treat rheumatoid arthritis (D2TRA). However, indicators for selection are lacking. This study aimed to identify optimal second-line b/tsDMARDs among the phase III treatment strategies based on European League Against Rheumatism (EULAR) RA management recommendations.

Methods: A total of 687 RA patients treated with second-line b/tsDMARDs (tumor necrosis factor inhibitor (n = 246), interleukin-6 receptor inhibitor [n = 195], cytotoxic T-lymphocyte-associated protein 4 immunoglobulin [n = 119], and Janus kinase inhibitor [n = 127]) were enrolled between October 2013 and April 2023. Rates of patients achieving Clinical Disease Activity Index (CDAI) remission and CDAI low disease activity (LDA), changes in CDAI, persistence rates, and adverse events within 24 weeks after treatment initiation were compared among the four groups. Propensity score-based inverse probability of treatment weighting (PS-IPTW) was used to minimize selection bias.

Results: After PS-IPTW adjustment, the Janus kinase inhibitor (JAKi) group had the highest persistence rate among the four groups. At 24 weeks, the JAKi group showed the greatest improvement in CDAI and the highest CDAI remission rate. Among patients treated with JAKi as second-line b/tsDMARDs, upadacitinib (UPA) was most likely to achieve CDAI remission at 24 weeks. The comparison between the UPA group (n = 32) and the non-UPA JAKi group (tofacitinib and baricitinib [n = 95]) showed comparable persistence rates but significantly lower CDAI scores and higher CDAI remission rate at 24 weeks in the UPA group. No significant difference was noted in the overall incidence of adverse events among the four groups treated with b/tsDMARDs or between the groups treated with JAKi.

Conclusions: Selecting JAKi, especially UPA, may effectively improve the disease activity for RA patients unresponsive to first-line b/tsDMARDs. Further large-scale studies are needed to clarify the efficacy and safety of UPA.

Trial registration: FIRST registry (approval number#04-23): October 2013, retrospectively registered.

Introduction: Axial spondyloarthritis (axSpA) is a chronic inflammatory condition associated with considerable pain and impaired health-related quality of life (HRQoL) for affected patients. Despite the documented increase in healthcare resource utilization (HRU) related to axSpA, few studies have explored the impact of diagnostic delays on these outcomes. This study sought to determine the association between diagnostic delay of axial spondyloarthritis (axSpA) and costs in the 3 years after diagnosis.

Methods: This is a retrospective, observational study based on routine follow-up data from adult patients with confirmed axSpA diagnosis in three tertiary Spanish hospitals. Sociodemographic and clinical variables were collected at diagnosis. Direct and indirect healthcare costs were estimated from healthcare resource use (HRU) and productivity losses. The correlation between diagnostic delay and total healthcare costs was analyzed.

Results: Eighty-two patients (62.2% men; mean age: 39.3 years at diagnosis) were included, mostly with radiographic axSpA (r-axSpA) (67.1%). The mean (standard deviation, SD) diagnostic delay was 10.1 (9.3) years, with a median (interquartile range, IQR) of 5.4 (2.3, 17.2) years. The mean total healthcare cost per patient accumulated over 3 years was €25,812.6 (direct: €16,384.7; indirect: €9427.9). Patients with longer diagnostic delay (> 5.4 years) had 57% higher total healthcare cost (€31,717.7 vs. €20,188.7, p = 0.029) and higher disease activity at diagnosis (BASDAI score 4.7 vs. 3.4, p = 0.007) and after 3 years (3.9 vs. 2.9, p = 0.042) compared to those with shorter delay (≤ 5.4 years).

Conclusions: The diagnostic delay in axSpA remains high and is associated with an increase in healthcare costs post-diagnosis. Actions to reduce diagnostic delay should be prioritized by healthcare systems to potentially improve outcomes and reduce long-term costs.

Introduction: Synovitis and enthesitis are key manifestations in psoriatic arthritis (PsA). This descriptive analysis investigated the association between improvement in synovitis and enthesitis, individually and combined, and improvement in patient-reported outcomes (PROs) including health-related quality of life (HRQoL) for patients with PsA from the SPIRIT-P1, SPIRIT-P2, and SPIRIT-H2H trials who presented with synovitis and enthesitis at baseline and received ixekizumab (IXE) treatment.

Methods: In this post hoc analysis, data are presented from patients with PsA treated with IXE every 4 weeks from two phase III studies (SPIRIT-P1 and SPIRIT-P2) and one phase IIIb/IV study (SPIRIT-H2H) who had both synovitis and enthesitis at baseline. Associations between improvements in synovitis and improvements in enthesitis were explored using Pearson analyses through week 52. Associations between improvements in both, either, and neither condition with improvements in PROs (36-item Short Form Health Survey Physical Component Score [SF-36 PCS], the European Quality-of-Life 5 Dimensions 5 Levels [EQ-5D-5L] including the EQ-5D Visual Analogue Score [VAS] and the EQ-health index, Patient's Global Assessment [PtGA], and pain VAS) were assessed descriptively through week 52.

Results: Results demonstrated the synergistic improvements in synovitis and enthesitis, individually or combined, and improvements in PROs including HRQoL, for patients treated with IXE through week 52. An association between improvements in synovitis and enthesitis symptoms was observed through week 52. Patients who achieved resolution of both synovitis and enthesitis reported highest improvements in SF-36 PCS, EQ-5D-5L, pain VAS, and PtGA.

Conclusion: Synergistic improvements in two key PsA domains, namely synovitis and enthesitis, and improvements in PROs including HRQoL, were observed for patients with PsA treated with IXE through week 52. These findings support PsA treatment goal aiming to achieve the lowest possible level of disease activity in all disease domains.

Trial registration numbers: SPIRIT-P1 (NCT01695239), SPIRIT-P2 (NCT02349295), and SPIRIT-H2H (NCT03151551).

There is accumulating evidence that inflammation is a key driver of atherosclerosis development and thrombotic complications. This pathophysiological mechanism explains, at least in part, the increased cardiovascular risk of patients with immune-mediated arthritis. Experimental and clinical studies have shown that tumour necrosis factor (TNF) plays a pathological role in both vascular and joint diseases, suggesting that TNF inhibitors (TNFis) may limit cardiovascular events in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) or spondyloarthritis (SpA). This review summarizes studies exploring the effects of TNFis on cardiovascular outcomes in patients with RA, PsA or SpA. Clinical studies suggest that TNFis reduce vascular inflammation and may improve (or prevent worsening of) endothelial dysfunction and arterial stiffness. There is evidence that TNFis reduce the incidence of cardiovascular events in patients with inflammatory arthritis compared with non-biological treatments, particularly in patients with rheumatoid arthritis. Fewer studies have compared the effects of different classes of biological therapy on outcomes, but found no significant difference in the risk of cardiovascular events between patients taking TNFis and other biological therapy. In contrast, patients at high cardiovascular risk may derive greater benefit from a TNFi than from a Janus kinase inhibitor (JAKi). The cardiovascular impact of JAKis is still under debate, with a recent safety warning. Targeted control of inflammation is a key strategy to reduce the risk of major adverse cardiovascular events in patients with inflammatory arthritis. Cardiovascular evaluation and risk stratification, using a multidisciplinary approach involving rheumatology and cardiology teams, are recommended to guide optimal immunomodulatory treatment.

Introduction: To evaluate the accuracy, reliability, and usability of Bend Ease, a novel smartphone-based digital health technology (DHT), which objectively self-measures spinal range of motion (SRoM) and remotely assesses morning stiffness.

Methods: This phase 1 study involved healthy volunteers (HV) and patients with axial spondyloarthritis (axSpA). Participants used Bend Ease by placing a phone against their chest during a forward-flexion bend, and the application collected and processed accelerometry data to measure bend angle in both clinical and at-home settings. Bend Ease measurements were compared to the video-based method (gold standard) and functional ability questionnaires.

Results: The study included 30 HV and 30 patients with axSpA. Bend Ease accurately measured forward-flexion bend angles, demonstrating strong correlation (r = 0.74) and concordance (ρ_c = 0.71) with measurement by video. Impaired bending for patients with axSpA relative to HV was most pronounced upon waking (65.3° versus 88.3°, P < 0.001), with increasing bend angle improvements observed for patients with axSpA at later time points (71.0° and 75.8° at 30 min and 1 h after waking, respectively). Waking bend angle correlated with self-reported morning stiffness and functional ability scores. A minimum clinically important difference in bend angle of 14 degrees was established for patients with axSpA, providing a benchmark for improvement. Bend Ease demonstrated robust test-retest reliability, and participants reported high usability.

Conclusions: Bend Ease is an accurate, reliable, and user-friendly tool for assessing SRoM. As the first DHT to objectively evaluate morning stiffness upon waking, Bend Ease provides valuable assessments of spinal mobility when it is most impaired.

Introduction: Celiac disease (CD) affects the small intestine, leading to a progressive disappearance of intestinal villi, and can be found in association with several other autoimmune and inflammatory conditions. The main objective of this study was to determine the prevalence and the clinical significance of anti-transglutaminase and anti-endomysium antibodies in patients diagnosed with early rheumatoid arthritis (RA) and spondyloarthritis (SpA).

Methods: We measured anti-transglutaminase and anti-endomysium antibodies in biobanked serum samples at inclusion in two French prospective multicenter cohorts of patients with suspected early rheumatoid arthritis (ESPOIR, n = 713) and spondyloarthritis (DESIR, n = 709). Results were compared with the clinical, laboratory, and radiographic findings obtained in patients during a 10-year follow-up period.

Results: In the DESIR cohort, anti-transglutaminase antibodies were evidenced at low levels (less than three times the upper limit of normal) in 2/709 (0.42%) patients and anti-endomysium antibodies in 0/709 (0%). In the ESPOIR cohort, anti-transglutaminase antibodies were evidenced in 6/713 (0.84%) patients and anti-endomysium antibodies in 1/713 (0.14%). Only the latter patient was confirmed to have celiac disease. Interestingly, this patient was ultimately diagnosed with Sjögren's disease, an autoimmune condition known to be associated with an increased risk of celiac disease.

Conclusion: The very low identified prevalence of anti-transglutaminase and anti-endomysium antibodies suggests a negligible risk of celiac disease in patients with early-stage RA or SpA, which are among the most common inflammatory rheumatic conditions. Consequently, routine screening for celiac disease via these antibodies in patients presenting with early inflammatory rheumatic conditions should not be performed except in case of clinical suspicion of celiac disease.