Rheumatology and Therapy最新文献

Introduction: Data assessing longer-term real-world effectiveness and treatment patterns with upadacitinib (UPA), a Janus kinase inhibitor, in rheumatoid arthritis (RA) are lacking. We assessed improvement in clinical and patient-reported outcomes and treatment patterns for up to 12 months among adult patients with RA initiating UPA.

Methods: Data were collected from the CorEvitas^® RA Registry (08/2019-04/2022). Eligible patients had moderate to severe RA (Clinical Disease Activity Index [CDAI] > 10) and follow-up visits at 6 or 12 months after UPA initiation. Outcomes were mean change from baseline, percentage achieving minimal clinically important differences (MCID) in clinical and patient-reported outcomes, and disease activity at follow-up. We evaluated clinical outcomes and therapy changes among patients with tumor necrosis factor inhibitor (TNFi) experience and among those receiving UPA as first-line therapy, as well as those receiving UPA as monotherapy versus as part of combination therapy. We further evaluated whether outcomes were similar among those that remained on therapy.

Results: Patients treated with UPA (6-month cohort, N = 469; 12-month cohort, N = 263) had statistically significant improvements (p < 0.001) in mean CDAI, tender/swollen joint counts, pain, and fatigue at follow-up. At 12 months, 46.0% achieved MCID in CDAI and 40.0% achieved low disease activity/remission. Overall, 43.0% discontinued UPA at 12 months; of those receiving combination treatment (N = 90) with conventional therapies and UPA, 42.2% (N = 38) discontinued conventional therapy. Findings were similar in the 6-month cohort and among subgroups. Changes from baseline and proportions of patients achieving MCID or clinical outcomes tended to be numerically lower among patients with TNFi experience and numerically higher among those receiving UPA as first-line therapy.

Conclusions: UPA initiation was associated with improvements in clinical and patient-reported outcomes, with meaningful clinical improvements regardless of prior TNFi experience, line of therapy, or concomitant use of conventional therapies. Further research is needed to better understand sustained response of UPA over longer treatment periods.

Introduction: Two biologic therapies for psoriatic arthritis (PsA), guselkumab and ustekinumab, have demonstrated superior efficacy versus placebo in clinical trials. However, no head-to-head studies have been conducted comparing these two treatments for PsA. The objective was to indirectly compare guselkumab and ustekinumab on joint and skin efficacy up to week 52, using pooled individual patient-level data (IPD) from PsA trials.

Methods: IPD, including baseline characteristics, American College of Rheumatology (ACR) scores and Psoriasis Area Severity Index (PASI) response from guselkumab (DISCOVER-1 and -2) and ustekinumab (PSUMMIT 1 and 2) trials were pooled. Differences in patient characteristics across trials were adjusted using multivariate logistic regression. Odds ratios (OR) were used to derive absolute response probabilities in the guselkumab trial population and were presented with 95% confidence intervals.

Results: Most baseline characteristics for guselkumab-treated patients (100 mg every 8 weeks [Q8W]; 100 mg every 4 weeks [Q4W]) were comparable to ustekinumab-treated patients (45/90 mg). In biologic-naïve patients, both guselkumab doses showed significantly higher ACR 20 (Q8W: 1.97; 1.37, 2.84; Q4W: 2.04; 1.40, 2.96) and PASI 90 (Q8W: 2.33; 1.52, 3.56; Q4W: 2.57; 1.67, 3.97) versus ustekinumab from week 16 onwards. In biologic-experienced patients, both guselkumab doses showed significantly higher ACR 20 (Q8W: 2.57; 1.11, 5.93; Q4W: 2.63; 1.12, 6.17) versus ustekinumab from week 24 onwards; for PASI 90, both guselkumab doses were superior to ustekinumab at week 16 and 52 (Q8W: 3.96; 1.39, 11.27; Q4W: 13.10; 4.18, 41.04). Guselkumab efficacy was similar and robust across primary, scenario, and sensitivity analyses.

Conclusions: IPD analysis demonstrated that both guselkumab doses were superior to ustekinumab for ACR 20 from weeks 16 (biologic-naïve) and 24 (biologic-experienced) onwards, and for PASI 90 at weeks 16 and 52 for both subgroups.

Introduction: Knee osteoarthritis (KOA) represents a widespread degenerative disease that causes pain and motor disability. Conservative treatments mainly focus on relieving symptoms, improving joint function, and trying to delay surgery. Safety and efficacy of hybrid cooperative complexes (2.4% sodium hyaluronate and 1.6% sodium chondroitin; HA-SC) for symptomatic KOA were investigated in a single-arm, prospective, pilot study.

Methods: Patients with a visual analogue scale (VAS) pain score ≥ 4 and Kellgren-Lawrence Grade < 4 received a single intraarticular HA-SC injection. Patients with a VAS score change from baseline ≤ 1 received a second injection at day 30. Device-related adverse events (DR-AEs)/adverse events (AEs) were primary endpoints. Secondary endpoints included Western Ontario and McMaster Universities Osteoarthritis Index LK 3.1 (WOMAC LK 3.1), VAS, patient global assessment of disease status (PtGA), and patient proportion needing a second injection.

Results: Of 83 patients with KOA (Kellgren-Lawrence Grade, 2-3), 34.9% had DR-AEs at day 7. No serious DR-AEs/AEs were reported. A significant (P < 0.0001) reduction over time in VAS pain score plus WOMAC pain, stiffness, physical function limitation, and total scores was reported. Median PtGA scores indicated a 'slight improvement' at most follow-up visits. Only 18.1% of patients required a second injection.

Conclusions: A single intraarticular HA-SC injection was safe, well-tolerated, and did not lead to major deterioration in terms of reducing knee pain, stiffness, and physical function limitation in patients with symptomatic KOA.

Introduction: Major salivary gland ultrasonography (SGUS) demonstrated its good metric properties as an outcome measure for diagnosing primary Sjögren's disease (SD). The objective was to assess SGUS reliability among sonographers with different levels of experience, using web training.

Methods: Sonographers from expert centers participated in the reliability exercise. Before exercises, training was done by videoconferencing. Reliability of the two most experienced sonographers (MES) was assessed and then compared to other sonographers. Intra-reader and inter-reader reliability of SGUS items were assessed by computing Cohen's κ coefficients.

Results: All sets were read twice by all 14 sonographers within a 4-month interval. Intra-reader reliability of MES was almost perfect for homogeneity, substantial for Outcome Measures in Rheumatology (OMERACT) scoring system (OMERACTss). Among LES (less experienced sonographers), reliability was moderate to almost perfect for homogeneity, fair to moderate for OMERACTss, and fair to almost perfect for binary OMERACTss. Inter-reader reliability between MES was almost perfect for homogeneity, substantial for diagnosis, moderate for OMERACTss, and substantial for binary OMERACTss. Compared to MES, reliabilities of LES were moderate to almost perfect for both homogeneity and diagnosis, only fair to moderate for OMERACTss, but increased in binary OMERACTss.

Conclusions: Videoconferencing training sessions in an international reliability exercise could be an excellent tool to train experienced and less-experienced sonographers. SGUS homogeneity items is useful to distinguish normal from abnormal salivary glands parenchyma independently of diagnosis. Structural damage evaluations by OMERACT scoring system is a new comprehensive score to diagnose patients with SD and could be easily used by sonographers in a binary method.

Introduction: The APPRAISE study was conducted to better understand the 12-month effectiveness, tolerability, and patient satisfaction with apremilast treatment for patients with psoriatic arthritis (PsA) in real-world settings.

Methods: APPRAISE (NCT03608657), a prospective, multicenter, observational study, enrolled adults with active PsA prescribed apremilast per routine care between July 2018 and March 2020. Patients were followed for 12 months with visits suggested every 4 months. The primary outcome measure was achievement of remission (REM) or low disease activity (LDA), defined as a Clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA) score ≤ 13.

Results: Of the 102 patients who enrolled, 45 (44.1%) discontinued the study by 12 months. Most patients (75.5%) had moderate or high disease activity, and 24.5% were in REM/LDA at baseline based on cDAPSA score. Achievement of cDAPSA REM/LDA was 63.7%, 67.2%, and 53.8% at months 4, 8, and 12, respectively. In those continuing in the study, significant improvements were seen in swollen and tender joint counts, pain visual analog scale, psoriasis body surface area, and complete dactylitis resolution. Enthesitis reduction was also observed. Improvements in treatment satisfaction and patient-reported outcomes, including Health Assessment Questionnaire-Disability Index and the 36-item Short Form physical and mental component scores, were observed over 12 months. The proportion of patients achieving a Patient-Acceptable Symptom State (PASS) increased significantly from baseline at months 4, 8, and 12 (P < 0.001). Apremilast was well tolerated; the most frequent adverse events (AEs) leading to discontinuation were diarrhea (9/102 [8.8%]), nausea (4/102 [3.9%]), and migraine (4/102 [3.9%]).

Conclusion: In this real-world study conducted in Canadian rheumatology clinics, apremilast demonstrated clinical effectiveness in patients with active PsA, along with patient satisfaction with treatment. Safety findings were consistent with previously reported clinical data.

Trial registration: ClinicalTrials.gov identifier, NCT03608657.

Introduction: To evaluate the effect of guselkumab on work productivity and nonwork daily activity impairment and general health status through 2 years in patients who were biologic-naïve with active psoriatic arthritis (PsA) in the phase 3 DISCOVER-2 clinical trial.

Methods: Adult patients with PsA were randomized to subcutaneous injections of guselkumab 100 mg every 4 weeks (Q4W); at weeks 0, 4, then every 8 weeks (Q8W); or placebo (through week 24 with crossover to guselkumab Q4W). Work productivity and nonwork daily activity impairment were assessed using the Work Productivity and Activity Impairment Questionnaire for PsA (WPAI-PsA) and patient-reported general health status using the EuroQol 5-Dimension 5-Level (EQ-5D-5L) Index and EQ-Visual Analog Scale (EQ-VAS). Least-squares (LS) mean changes from baseline in WPAI-PsA domains and EQ-5D-5L/EQ-VAS were assessed through week 100. Changes in employment status were utilized to estimate potential indirect savings from improved work productivity.

Results: Of 739 randomized patients, 738 had available baseline data for the analyses (Q4W 245; Q8W 248; placebo 245). At week 24, greater improvements in work productivity, nonwork daily activity, and EQ-5D-5L/EQ-VAS were observed in the Q4W and Q8W groups versus the placebo group. At week 100, LS mean reductions in work productivity impairment (- 23.8% to - 28.0%) and nonwork daily activity impairment (- 26.6% to - 29.2%) and improvements in EQ-5D-5L/EQ-VAS (0.14 to 0.15/21.2 to 25.0) were maintained in patients receiving guselkumab. Among patients employed at baseline, 12.1-16.4% were not employed at week 100, and 20.0-25.3% shifted from not employed at baseline to employed at week 100. Potential yearly indirect cost savings (USD) from improved work productivity at week 100 ranged from $16,529 to $19,409.

Conclusion: Patients with active PsA treated with guselkumab demonstrated reduced impairment in work productivity and nonwork daily activity, together with improvement in general health status and substantial potential cost savings, over a 2-year period.

Trial registration: Clinicaltrials.gov identifier: NCT03158285.

Introduction: There is a lack of data on the use of thermography for elbow joint inflammation assessment among patients with rheumatoid arthritis (RA). Hence, we aimed to compare thermography with ultrasonography (a more established imaging modality for joint inflammation assessment) in the assessment of inflammation in the elbows of patients with RA.

Methods: Standardised minimum (Tmin), maximum (Tmax) and average (Tavg) temperatures at each elbow (medial, lateral, posterior and anterior aspects) were summed to obtain the thermographic parameters MIN, MAX and AVG, respectively. Ultrasound parameters of elbow joint inflammation included total greyscale (TGS) and total power Doppler (TPD) scores. Pearson's correlation coefficient was utilized for correlation analysis between parameters. The relationship between parameters was characterized using simple linear regression.

Results: Sixty elbows were evaluated from 30 patients with RA in this cross-sectional study. Thermographic parameters (MIN, MAX and AVG) showed significant correlation (P < 0.05) with (1) TPD scores at both elbows (correlation coefficient ranging 0.40 to 0.55) and (2) TGS scores at the right elbow (correlation coefficient ranging 0.39 to 0.42). A statistically significant relationship (P values ranging from 0.002 to 0.033) between parameters was demonstrable as follows: (1) MIN, MAX and AVG versus TPD scores (bilateral elbows) and (2) MIN, MAX and AVG versus TGS scores (right elbow).

Conclusion: Thermographic temperatures have been demonstrated to correlate with ultrasound-detected joint inflammation at the elbow in patients with RA. The association is more consistently observed with ultrasound PD joint inflammation than its GS counterpart.

Introduction: This study aimed to characterize patient-reported outcomes from social media conversations in the gout community. The impact of management strategy differences on the community's emotional states was explored.

Methods: We analyzed two social media sources using a variety of natural language processing techniques. We isolated conversations with a high probability of discussing disease management (score > 0.99). These conversations were stratified by management type: proactive or reactive. The polarity (positivity/negativity) of language and emotions conveyed in statements shared by community members was assessed by management type.

Results: Among the statements related to management, reactive management (e.g., urgent care) was mentioned in 0.5% of statements, and proactive management (e.g., primary care) was mentioned in 0.6% of statements. Reactive management statements had a significantly larger proportion of negative words (59%) than did proactive management statements (44%); "fear" occurred more frequently with reactive statements, whereas "trust" predominated in proactive statements. Allopurinol was the most common medication in proactive management statements, whereas reactive management had significantly higher counts of prednisone/steroid mentions.

Conclusions: A unique aspect of examining gout-related social media conversations is the ability to better understand the intersection of clinical management and emotional impacts in the gout community. The effect of social media statements was significantly stratified by management type for gout community members, where proactive management statements were characterized by more positive language than reactive management statements. These results suggest that proactive disease management may result in more positive mental and emotional experiences in patients with gout.

Introduction: Anemia and malnutrition are recognized indicators of suboptimal physical condition in chronic inflammatory diseases. This study aimed to examine the association between anemia, low body mass index (BMI), and clinical outcomes in axial spondyloarthritis (axSpA).

Method: This cross-sectional analysis utilized data from the multicenter ChinaSpA cohort. A total of 4146 participants with axSpA were categorized into four groups based on BMI and hemoglobin levels: those with both anemia and low BMI, those with anemia only, those with low BMI only, and those with neither condition. Logistic regression analyses were performed to analyze the association between anemia, low BMI, inflammation status, functional impairment, and disease activity.

Results: Anemia was present in 13.94%, low BMI in 11.99%, and both conditions in 2.15% of axSpA participants. Those with both anemia and low BMI showed significantly higher levels of inflammation (hypersensitive C-reactive protein [hsCRP] 30.60 mg/L vs. 8.44 mg/L), functional impairment (Bath Ankylosing Spondylitis Functional Index [BASFI] 3.80 vs. 2.10), and disease activity (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] 4.52 ± 2.04 vs. 3.67 ± 2.21; Ankylosing Spondylitis Disease Activity Score calculated with C-reactive protein [ASDAS_CRP] 3.51 ± 1.10 vs. 2.62 ± 1.21) compared to those without these conditions. After adjusting for sex and age, significant associations were observed between elevated hsCRP levels and the presence of low BMI (odds ratio [OR] 1.44, 95% CI 1.17-1.78), anemia (OR 1.91, 95% CI 1.56-2.32), and their concurrent presence (OR 3.59, 95% CI 2.22-5.80). Similarly, increased BASFI was significantly associated with low BMI (OR 1.57, 95% CI 1.25-1.97), anemia (OR 1.47, 95% CI 1.19-1.80), and their combination (OR 3.11, 95% CI 2.02-4.78).

Conclusion: All-cause anemia and low BMI are prevalent complications in patients with axSpA, exhibiting a significant correlation with elevated inflammation status and functional impairment. The simultaneous occurrence of anemia and low BMI particularly exacerbates clinical outcomes, emphasizing the critical role of comprehensive nutritional assessment and management in the therapeutic strategy for axSpA.

Introduction: Nonsteroidal anti-inflammatory drugs (NSAIDs) are the primary treatment for osteoarthritis (OA), but prolonged use has adverse effects and varying efficacy. Among NSAIDs, imrecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, reduces side effects yet remains ineffective for half of the patient population. This study aims to identify biomarkers for early evaluation of imrecoxib efficacy in OA for personalized therapy optimization.

Methods: From September 2021 to January 2022, imrecoxib was administered to patients with OA at Nanjing Drum Tower Hospital. Plasma samples from these patients underwent proteomic analysis through the four-dimensional data-independent acquisition (4D-DIA) method, followed by bioinformatics analysis. Potential differentially expressed proteins (DEPs) were validated using enzyme-linked immunosorbent assays (ELISA).

Results: Sixty-six patients with knee OA were included and divided into responders (n = 35) and non-responders (n = 31). Proteomic analysis was conducted on 15 patients from each group, with ELISA validation for every patient. We found 140 DEPs between the two groups after imrecoxib treatment, characterized by 29 proteins showing upregulation and 111 displaying downregulation (P < 0.05, fold change >  ± 1.2). Galectin-1 (LGALS1), galectin-3 (LGALS3), and cluster of differentiation 44 (CD44) were identified as potential markers for evaluating clinical response to imrecoxib in OA following ELISA validation.

Conclusion: This study successfully identified biomarkers for evaluating imrecoxib's clinical response in patients with OA using 4D-DIA technology. These biomarkers may play a vital role in future personalized OA treatment strategies, pending further confirmation.