Arthritis Research & Therapy最新文献

Background: The development of personalized approaches in psoriatic arthritis (PsA) is challenging due to unclear patient phenotypes and trajectories. Machine learning (ML) could help to identify homogeneous patient groups. The objective of this analysis was to classify patients with PsA into distinct phenotypes using ML.

Methods: A post hoc analysis of PsA patients treated with risankizumab for ≤ 4 years (196 weeks) from KEEPsAKE 1 and KEEPsAKE 2. The phenotypes were based on baseline demographics and clinical characteristics using unsupervised ML (a finite mixture model). Response to risankizumab at 4 years was defined as minimal disease activity (MDA) and Disease Activity in PsA (DAPSA) low disease activity (LDA).

Results: A total of 1119 patients were classified into 5 distinct PsA phenotypes: Moderate to High Disease Activity (40.3% of patients) - characterized by lower tender joint count (TJC) and swollen joint count (SJC), dactylitis, and enthesitis; Enthesitis and Large Joints Dominant (20.8% of patients) - characterized by enthesitis and mainly active large joints; Very High Disease Activity (14.0% of patients) - characterized by high TJC/SJC, dactylitis, and enthesitis; Hand Dominant (13.8% of patients) - characterized by active joints primarily in the hands; Dactylitis and Feet Dominant (11.1% of patients) - characterized by dactylitis and active joints primarily in the feet. At 4 years, risankizumab demonstrated efficacy across all phenotypes (MDA and DAPSA LDA; range: 42.9% to 58.8% of patients and 66.0% to 82.0% of patients, respectively), with highest responses observed in the Moderate to High Disease Activity and Dactylitis and Feet Dominant phenotypes.

Conclusions: Five distinct PsA phenotypes were identified in patients starting risankizumab. Moderate to High Disease Activity, the most frequent phenotype, showed the highest response, though risankizumab demonstrated efficacy across all phenotypes. These results are a first step toward more personalized medicine for patients with PsA.

Trial registration: ClinicalTrials.gov: KEEPsAKE 1, NCT03675308; KEEPsAKE 2, NCT03671148.

Background: Birth outcomes associated with conventional synthetic and biologic disease-modifying antirheumatic drugs (csDMARDs, bDMARDs and tsDMARDs) in fathers with autoimmune rheumatic diseases (AIRDs) is not well understood.

Methods: To examine the impact of paternal exposure to csDMARDs, bDMARDs or tsDMARDs on birth outcomes of offspring, specifically with regards to small for gestational age infants, preterm labor, and congenital abnormalities. We constructed a population-based birth cohort with fathers diagnosed with AIRDs from 2004 to 2020 using data from the Maternal and Child Health Database, Taiwan Birth Certificate Registry, and Taiwan National Health Insurance Research Data. Paternal preconception exposure was fathers who had been prescribed immunosuppressants or biologic drugs between 38 and 60 weeks before their newborn's delivery date. Inverse probability of treatment-weighted (IPTW) logistic regression models were used to assess the effects of variables on associations of interest considering other covariates.

Results: The study analyzed 42,493 births to fathers with autoimmune conditions, with 14.3% of fathers exposed to immunosuppressants or biologic medications during the preconception period. The IPTW logistic regression analysis showed drug-specific risks during the preconception in preterm birth, birth defects, or very small for gestational age (VSGA). Individually, methotrexate showed no adverse effect on birth outcomes. However, certain medications, such as ciclosporin was associated with an increased risk of VSGA and preterm by 45% (95% confidence interval [CI] = 1.19 ~ 1.76) and 51% (95% CI = 1.35 ~ 1.70) respectively. Azathioprine (OR = 1.47, 95% CI = 1.31 ~ 1.65) was linked to higher birth defect risks, as were non-TNFis (OR = 1.69, 95% CI = 1.48 ~ 1.93) and tsDMARDs (OR = 5.19, 95% CI = 2.33 ~ 11.39). Fathers who received csDMARDs alone or combined with bDMARDs or tsDMARDs had an increased risk of birth defects (OR = 1.71, 95% CI = 1.47-2.00). Specific birth defects associated with bDMARDs included cardiovascular anomalies (OR: 1.61; 95% CI: 1.37-1.89), oral clefts (OR: 1.62; 95% CI: 1.15-2.29), and musculoskeletal defects (OR: 2.29; 95% CI: 1.82-2.89). Fathers exposed to csDMARDs combined with bDMARDs or tsDMARDs had increased risks of cardiovascular anomalies, oral clefts, and musculoskeletal defects.

Conclusion: While paternal use of methotrexate did not associate with adverse birth outcome, exposure to other immunosuppressants or biologic drugs may link to possible adverse birth outcomes despite small event numbers. This result highlight the importance of further clarification of drug safety in this field and medication use before planning a pregnancy, even in male patients.

Background: Bacterial (i.e., septic) arthritis requires prompt source control, including drainage of the infected synovial fluid, often through arthrocentesis (needle aspiration) or surgical intervention, in combination with antibiotics to prevent joint damage; however, when surgical intervention is required, conventional arthroscopy can lead to treatment delays and anesthesia-related complications. To overcome these delays, needle arthroscopy was recently developed to offer the possibility of 2-mm diameter arthroscopy lavage under local anesthesia. The purpose of this study was to prospectively evaluate bedside needle arthroscopy under local anesthesia to demonstrate its potential as an effective, minimally invasive alternative for timely diagnosis and joint lavage in patients with (suspected) native bacterial arthritis in a real-world clinical practice setting.

Methods: Over a 30-month period, this prospective, double center cohort study included patients with either confirmed (positive synovial fluid culture) or highly suspected (≥ 2 local signs and ≥ 1 systemic sign) native joint bacterial arthritis. The primary outcome was the need for reoperation (conventional arthroscopy or arthrotomy) within 30 days. Bivariate analysis assessed differences in patient and treatment characteristics between successful and failed needle arthroscopic debridement.

Results: Forty-two patients (44 native joints) underwent needle arthroscopy. The mean age was 67 years (SD 16), the mean BMI was 26.8 kg/m² (SD 3.9), and 69% were male. The knee (n = 34, 77%) was the most commonly involved joint. Within 30 days, 14% (6/44; 95% CI 5-27%) required a reoperation (conventional arthroscopy or arthrotomy). Two parameters were identified as risk factors for failure of a single debridement: the baseline level of ESR (112 mm/hr vs. 57 mm/hr, p = 0.027) and purulent synovial fluid (67% vs. 11%; p = 0.011). No serious procedure-related complications were observed.

Conclusions: A single bedside needle arthroscopy was effective in treating 86% of patients with confirmed or suspected native joint bacterial arthritis in a real-world practice, avoiding the need for general anesthesia or conventional surgery. This approach represents a safe and effective, minimally invasive alternative that can be rapidly implemented, enabling early joint lavage and potentially reducing the risk of secondary osteoarthritis.

Trial registration: We pre-registered this trial on the Dutch Trial Register, later called CCMO (NTR 21076, CCMO NL78387.018.21).

Background: Osteoarthritis (OA) is the leading cause of pain worldwide. However, clinical discordance between pain and cartilage damage presents challenges in determining the mechanisms of OA pain, thus creating a need for well-controlled models that probe the separable mechanisms of structural damage and knee pain. We previously identified that deletion of complement factor D (FD) results in increased pressure-pain hyperalgesia despite cartilage protection after destabilization of the medial meniscus (DMM) surgery. However, how these discordant OA phenotypes manifest is not understood. We employed a novel targeted lipidomics approach to elucidate the role of eicosanoids in FD-mediated pain. We hypothesize that the absence of Cfd (FD^-/-) will protect cartilage but cause increased pressure-pain hyperalgesia and eicosanoid dysregulation persisting throughout OA development.

Methods: Male and female FD^-/- and wild-type (WT) mice were challenged with DMM or remained naïve at 16 weeks old. Pressure-pain hyperalgesia was measured every two weeks for 8 weeks post-DMM. A second cohort was evaluated at 2 weeks post-DMM to investigate DMM injury response. Structural damage was scored using the Modified Mankin system. Eicosanoid profiles were characterized via liquid chromatography-mass spectrometry (LC-MS) on serum and synovial fluid samples. Statistical analysis was performed with unpaired t-test or two-way ANOVA with Sidak's posthoc test, p < 0.05.

Results: Unlike WT mice, FD^-/- mice exhibited no differences in Modified Mankin scores 8 weeks post-DMM in both sexes. As expected, FD^-/- and WT hyperalgesia was present at 2 weeks, persisted through 8 weeks, and was not associated with knee structural changes. Despite both sexes exhibiting similar levels of hyperalgesia, eicosanoid profiles differed. Male FD^-/- demonstrated greater pain-driving (12-HETE, 13-HODE) and lower pain-driving (15-HETE) and pain-suppressing (14-HDHA) abundances of eicosanoids compared to WT. Paradoxically, female FD^-/- exhibited bi-directional differences in pain-suppressive factors (palmitoyl ethanolamide, EPA, 14-HDHA) and lower abundances of pro-inflammatory arachidonic acid compared to WT.

Conclusion: The absence of Cfd protects cartilage but does not prevent hyperalgesia after DMM. Changes in eicosanoid profiles suggests that loss in FD drives pain acutely and creates a hyperalgesia phenotype early in response to DMM. Eicosanoid profiling is a novel tool to mechanistically determine pain drivers in osteoarthritis.

Background: The risk of non-Hodgkin's lymphoma in patients with primary Sjögren's syndrome (pSS) is well established. However, the association between pSS and the risk of gastrointestinal cancers remains underexplored. This study aims to assess the risk of gastrointestinal cancers in pSS patients in Korea compared with the general population.

Methods: We included 320,082 participants from National Health Insurance Service-National Sample Cohort (NHIS-NSC) database. Of these, there were 850 patients with pSS and 319,232 in the non-pSS group. All participants were followed-up until 2019 or the development of gastrointestinal cancers, whichever occurred first. Hazard ratio (HR) and 95% confidence intervals (95% CI) for gastrointestinal cancers were calculated by multivariable Cox proportional hazards models.

Results: Compared with the non-pSS group, patients with pSS had a higher risk of developing all gastrointestinal cancers, but the association did not reach statistical significance (adjusted HR: 1.240, 95% CI: 0.990-1.543). Site-specific analyses showed that pSS patients had a higher risk of colorectal cancer (adjusted HR: 1.597, 95% CI: 1.122-2.273) and pancreatic cancer (adjusted HR: 2.294, 95% CI: 1.267-4.151). The association was found to be more prominent in females and elderly (aged ≥ 60) individuals according to subgroup analyses.

Conclusions: pSS was associated with increased risks of colorectal and pancreatic cancers, particularly among females and older adults. Further research should explore the underlying mechanisms and the impact of pSS duration and severity on cancer risk.