OBJECTIVE: To investigate the efficacy, safety, pharmacokinetics and pharmacodynamics of nipocalimab in participants with moderate to severe active rheumatoid arthritis (RA) and inadequate response or intolerance to ≥1 antitumour necrosis factor agent.
METHODS: In this phase 2a study, participants with RA seropositive for anticitrullinated protein antibodies (ACPA) or rheumatoid factors were randomised 3:2 to nipocalimab (15 mg/kg intravenously every 2 weeks) or placebo from Weeks 0 to 10. Efficacy endpoints (primary endpoint: change from baseline in Disease Activity Score 28 using C reactive protein (DAS28-CRP) at Week 12) and patient-reported outcomes (PROs) were assessed through Week 12. Safety, pharmacokinetics and pharmacodynamics were assessed through Week 18.
RESULTS: 53 participants were enrolled (nipocalimab/placebo, n=33/20). Although the primary endpoint did not reach statistical significance for nipocalimab versus placebo, a numerically higher change from baseline in DAS28-CRP at Week 12 was observed (least squares mean (95% CI): -1.03 (-1.66 to -0.40) vs -0.58 (-1.24 to 0.07)), with numerically higher improvements in all secondary efficacy outcomes and PROs. Serious adverse events were reported in three participants (burn infection, infusion-related reaction and deep vein thrombosis). Nipocalimab significantly and reversibly reduced serum immunoglobulin G, ACPA and circulating immune complex levels but not serum inflammatory markers, including CRP. ACPA reduction was associated with DAS28-CRP remission and 50% response rate in American College of Rheumatology (ACR) criteria; participants with a higher baseline ACPA had greater clinical improvement.
CONCLUSIONS: Despite not achieving statistical significance in the primary endpoint, nipocalimab showed consistent, numerical efficacy benefits in participants with moderate to severe active RA, with greater benefit observed for participants with a higher baseline ACPA.
BACKGROUND: NCT04991753.

BACKGROUND: The nature of the relationship between inflammation, cardiovascular (CV) risk factors and atherosclerosis in axial spondyloarthritis (axSpA) remains largely unknown and sex differences in this regard are yet to be assessed.
METHODS: Study including 611 men and 302 women from the Spanish multicentre AtheSpAin cohort to assess CV disease in axSpA. Data on CV disease risk factors were collected both at disease diagnosis and at enrolment, and data on disease activity, functional indices and carotid ultrasonography only at enrolment.
RESULTS: After a median disease duration of 9 years, patients of both sexes who at disease diagnosis had elevated acute phase reactants (APRs), more frequently had hypertension and obesity. The same occurred with dyslipidaemia in men and with diabetes mellitus in women. At enrolment, CV risk factors were independently associated with APR and with activity and functional indices, with various sex differences. C reactive protein (CRP) values were inversely associated with HDL-cholesterol in men (β coefficient: -1.2 (95% CI: -0.3 to -0.07) mg/dL, p=0.001), while erythrocyte sedimentation rate values were positively associated with triglycerides in women (β coefficient: 0.6 (95% CI: 0.04 to 1) mg/dL, p=0.035). Furthermore, only women showed an independent relationship between insulin resistance parameters and APR or disease activity. Both men and women with high-very high CV risk according to the Systematic Assessment of Coronary Risk Evaluation 2 and CRP levels higher than 3 mg/L at diagnosis of the disease presented carotid plaques significantly more frequently than those with normal CRP levels at disease diagnosis.
CONCLUSIONS: Inflammation is associated with atherosclerosis and CV disease in axSpA. A gender-driven effect is observed in this relationship.

Osteoarthritis (OA) causes a massive disease burden with a global prevalence of nearly 23% in 2020 and an unmet need for adequate treatment, given a lack of disease-modifying drugs (DMOADs). The author reviews the prospects of active DMOAD candidates in the phase 2/3 clinical trials of drug development pipeline based on key OA pathogenetic mechanisms directed to inflammation-driven, bone-driven, and cartilage-driven endotypes. The challenges and possible research opportunities are stated in terms of the formulation of a research question known as the PICO approach: (1) population, (2) interventions, (3) comparison or placebo, and (4) outcomes.

Imaging methods capable of detecting inflammation, such as MR imaging and ultrasound, are of paramount importance in rheumatic disease management, not only for diagnostic purposes but also for monitoring disease activity and treatment response. However, more advanced stages of arthritis, characterized by findings of cumulative structural damage, have traditionally been accomplished by radiographs and computed tomography. The purpose of this review is to provide an overview of imaging of some of the most prevalent inflammatory rheumatic diseases affecting the lower limb (osteoarthritis, rheumatoid arthritis, and gout) and up-to-date recommendations regarding imaging diagnostic workup.

OBJECTIVE: This study aimed to assess the effectiveness of exercise therapy for Axial spondyloarthritis (axSpA) patients.
METHODS: From the database inception to March 2024, we searched PubMed (via Medline), Cochrane Library, Embase, Web of Science, Scopus, and SPORTDiscus for all relevant publications without any language restriction.
METHODS: We included randomized controlled trials (RCTs) for axSpA patients in which at least one group received exercise therapy.
METHODS: Two independent reviewers assessed the quality of the literature using the Cochrane Collaboration Risk of Bias Tool 2.0. The outcomes were ankylosing spondylitis (AS) disease activity score (ASDAS), Bath AS disease activity index (BASDAI), Bath AS functional index (BASFI), Bath AS metrology index (BASMI), 6-minute walk distance (6MWT), Chest expansion capacity, Peak oxygen consumption (VO2peak), pain, fatigue, C-reactive protein (CRP), and Eythrocyte sedimentation rate (ESR).
RESULTS: A total of 20 RCTs, including 1,670 patients, were included in this study. Compared with the control group, exercise therapy improved BASFI (weighted mean difference [WMD]: -0.49, 95% confidence interval [CI]: -0.65 to -0.32, I2= 3.4%, P=0.414), BASMI (WMD: -0.49, 95% CI: -0.87 to -0.11, I2= 71.9%, P=0.679), BASDAI (WMD: -0.78, 95% CI: -1.08, -0.47, I2=55.9%, P=0.021), ASDAS (WMD: -0.44, 95% CI: -0.64 to -0.24, I2 =0.0%, P=0.424), VO2peak (WMD: 3.16, 95% CI: 1.37 to 4.94, I2=0.0%, P=0.873), 6MWT (WMD: 27.64, 95% CI: 12.04 to 43.24, I2= 0.0%, P=0.922), Pain (standardized mean difference [SMD]: -0.47, 95% CI: -0.74 to -0.21, I2= 66.0%, P=0.046) and Fatigue (SMD: -0.49, 95% CI: -0.71 to -0.27, I2= 0.0%, P=0.446). However, no significant benefit was found in Chest expansion, CRP, and ESR outcomes.
CONCLUSIONS: Exercise therapy is an effective strategy for improving disease control and symptom relief in axSpA.

BACKGROUND: Total knee arthroplasty (TKA) is performed on approximately 790,000 patients annually in the United States and is projected to increase to 1.5 million by 2050. This study aimed at assessing the use of preoperative cryoneurolysis on patients undergoing TKA by analyzing: 1) pain severity; 2) opioid use; 3) functional status; and 4) sleep disturbance over 6 months following discharge.
METHODS: Patients enrolled in the Innovations in Genicular Outcomes Registry (iGOR) between September 2021 and February 2024 were followed for 6 months. Our analyses included patients undergoing unilateral primary TKA with no pre-operative opioid prescription who either received, or did not receive, cryoneurolysis. Baseline patient demographics were collected before TKA and tabulated. Pain management was assessed via the Brief Pain Inventory-Short Form (BPI-SF) instrument for pain severity. Sleep disturbance was measured using the Patient-Reported Outcomes Measurement Information System (PROMIS) questionnaire. Each outcome measure was assessed prior to TKA, weekly, and at monthly follow-up. Data was analyzed by a generalized linear mixed-effect regression model to compare cryoneurolysis versus control patients, with a P < 0.05 as significant.
RESULTS: There were 80 patients who were treated with preoperative cryoneurolysis, while 60 control patients did not have treatment. Patients receiving cryoneurolysis experienced significantly lower pain severity and sleep disturbance over the 6-month follow-up than control patients (P = 0.046). Cryoneurolysis was also associated with a trend toward greater functional improvement that did not reach statistical significance (P = 0.061). Further, patients who underwent cryoneurolysis were 72% less likely than controls to take opioids over six months following discharge (P <0.001).
CONCLUSIONS: Pre-operative cryoneurolysis therapy in opioid-naïve patients undergoing TKA is associated with improved pain, decreased opioid use, and improved sleep disturbance for 6 months postoperatively. Cryoneurolysis, a non-opioid pain relief modality administered pre-operatively, demonstrated substantial benefits in patients who underwent TKA.

OBJECTIVE: This study aimed to analyze the associations between rheumatoid arthritis (RA) and all-cause mortality and cardiovascular disease (CVD)-related mortality using data from the National Health and Nutrition Examination Survey (NHANES) and examine the potential mediating role of depression in these correlations.
METHODS: 19,165 participants across five NHANES cycles from 2007 to 2016 participated in this study. Multifactorial Cox regression models between RA, depression and two mortality outcomes and multifactorial regression models between RA and depression were constructed to examine their associations. The mediating role of depression has also been investigated.
RESULTS: The prevalence of RA in this study was 6.57 %, the all-cause mortality of RA patients was 20.57 %, and the CVD-related mortality was 6.12 %. In the fully adjusted model, RA was associated with all-cause mortality [hazard ratio (HR) = 1.28, 95 % confidence interval (CI) = 1.12 to 1.48] and CVD-related mortality (HR = 1.33, 95 % CI = 1.03 to 1.72), without detectable interaction among subgroups (P for interaction >0.05). RA also had a positive correlation with depression. Depression score demonstrated pronounced mediating effects in the connections between RA and two types of mortality, with mediation ratios of 18.2 % and 18.9 %.
CONCLUSIONS: The diagnosis of RA is self-reported and may be subject to recall bias.
CONCLUSIONS: RA was positively correlated with the risk of all-cause mortality and CVD-related mortality. Depression partially mediates these associations. Close attention to and active improvement of mental health in RA patients will be critical to decrease all-cause mortality and CVD-related mortality.

The human gut microbiome plays a crucial role in immune function. The synbiotic consortium or Defined Microbial Assemblage™ (DMA™) Medical Food product, SBD121, consisting of probiotic microbes and prebiotic fibers was designed for the clinical dietary management of rheumatoid arthritis. A 28-day repeated administration study was performed to evaluate the oral toxicity of SBD121 in male and female rats (age/weight at study start: 60 days/ 156-264 grams) administered levels of 0, 4.96 x 1010, 2.48 x 1011, or 4.96 x 1011 colony forming units (CFU)/kg-bw. No treatment related changes in ophthalmological effects, mortality, morbidity, general health and clinical observations, urinalysis, hematology, serum chemistry, absolute or relative organ weights, gross necropsy, or histopathology. A significant decrease in body weight was reported in females in the low and high-concentration groups, which corresponded in part with a significant decrease in food consumption. Results of the functional observation battery indicated front grip strength was significantly greater in the high-concentration males compared to the controls; however, this effect was not considered adverse. Based on these findings, the administration of the Medical Food SBD121 to male and female rats has a no-observable adverse effect level (NOAEL) at the highest level tested of 4.96 x 1011 CFU/kg-bw.

Rheumatoid arthritis (RA) is an immune-mediated disease that necessitates a thorough understanding of its intricate pathophysiological mechanism for precise and effective therapeutic targeting. The European League Against Rheumatism (EULAR) has established guidelines for RA treatment, endorsing monotherapy or combination therapy with corticosteroids and synthetic disease-modifying antirheumatic drugs (sDMARDs). This review delves into clinical trials and research outcomes related to combination drug delivery, with an emphasis on the role of natural products in combination with synthetic drugs. Given the significant adverse effects associated with systemic administration, topical delivery has emerged as an alternative avenue for effective management of RA.

OBJECTIVE: Rheumatoid arthritis (RA) is a chronic systemic disease characterized by inflammatory synovitis, and genetic factors play the greatest role in RA. This study aimed to investigate the relationship between Toll-like receptor 10(TLR10) gene polymorphisms and susceptibility to RA.
METHODS: A total of 271 patients with RA and an equal number of healthy controls were included, and the TLR10 rs2101521, rs10004195 and rs11725309 loci were genotyped by time-of-flight mass spectrometry.
RESULTS: Compared with healthy controls, Individuals carrying the rs2101521 G allele had an increased risk of developing RA (P = 0.01; odds ratio (OR) = 1.367; 95 % confidence interval (CI): 1.076-1.736). Individuals with the rs2101521 GG genotype had a greater risk of RA (P = 0.01; OR = 1.816; 95 % CI: 1.161-2.984). Stratified analysis demonstrated a greater prevalence of positive anti-cyclic citrullinated peptide (CCP)antibody in patients carrying the rs2101521 G allele (P = 0.03). Additionally, patients with the rs11725309 CT genotype had elevated levels of C-reactive protein (CRP)(P = 0.007).
CONCLUSIONS: In conclusion, TLR10 gene polymorphisms are associated with RA susceptibility.