IL-6 induces chondrocyte catabolism mainly via Stat3 signalling, a pathway activated in cartilage from joint subjected to DMM. Systemic blockade of IL-6 or STAT-3 can alleviate DMM-induced OA in mice.

No abstract

Background Various observations have suggested that the course of COVID-19 might be less favourable in patients with inflammatory rheumatic and musculoskeletal diseases receiving rituximab compared with those not receiving rituximab. We aimed to investigate whether treatment with rituximab is associated with severe COVID-19 outcomes in patients with inflammatory rheumatic and musculoskeletal diseases.Methods In this cohort study, we analysed data from the French RMD COVID-19 cohort, which included patients aged 18 years or older with inflammatory rheumatic and musculoskeletal diseases and highly suspected or confirmed COVID-19. The primary endpoint was the severity of COVID-19 in patients treated with rituximab (rituximab group) compared with patients who did not receive rituximab (no rituximab group). Severe disease was defined as that requiring admission to an intensive care unit or leading to death. Secondary objectives were to analyse deaths and duration of hospital stay. The inverse probability of treatment weighting propensity score method was used to adjust for potential confounding factors (age, sex, arterial hypertension, diabetes, smoking status, body-mass index, interstitial lung disease, cardiovascular diseases, cancer, corticosteroid use, chronic renal failure, and the underlying disease [rheumatoid arthritis vs others]). Odds ratios and hazard ratios and their 95% CIs were calculated as effect size, by dividing the two population mean differences by their SD. This study is registered with ClinicalTrials.gov, NCT04353609.

ObjectivesIn patients with gout, maintaining too low serum uric acid (SUA) level with urate-lowering therapy is a concern because uric acid is thought to be neuroprotective. However, the relation between SUA and dementia remains debated. This study aimed to investigate the impact of SUA level on the incidence of dementia.MethodsWe assessed the longitudinal association between SUA level and incident dementia (Diagnostic and Statistical Manual of Mental Disorders Version IV (DSM-IV) criteria) in a large cohort of healthy older people from the community (Three-City Dijon cohort). Additionally, we investigated the relation between SUA level and MRI markers of brain ageing (white matter hyperintensity volume (WMHV), lacunes and hippocampal volume).ResultsThe study sample comprised 1598 people (mean (SD) age 72.4(4.1) years, 38.3% male). During the 13,357 person-years of follow-up (median duration: 10.1 years), dementia developed in 110 participants (crude incidence rate: 8.2/1000 person-years). After multiple adjustments, the multivariate HR with the highest (≥75th percentile) versus lowest SUA level was 1.79 (95% CI 1.17 to 2.73; p=0.007). The association was stronger with vascular or mixed dementia (HR=3.66 (95% CI 1.29 to 10.41), p=0.015) than Alzheimer’s disease (HR=1.55 (95% CI 0.92 to 2.61), p=0.10). There was a non-significant trend towards an association between high SUA level and extensive WMHV (p=0.10), a biomarker of small vessel disease, but not hippocampal volume (p=0.94) or lacunes (p=0.86). The association between SUA level and vascular or mixed dementia might be affected by interim strokes.ConclusionsRisk of dementia, especially vascular or mixed dementia, may be increased with high SUA levels in elderly people.

No abstract

ObjectiveTo evaluate the efficacy of tocilizumab, an antibody against IL-6 receptor, in patients with hand osteoarthritis.MethodsThis was a multicentre, 12-week, randomised, double-blind, placebo-controlled study from November 2015 to October 2018. Patients with symptomatic hand osteoarthritis (pain ≥40 on a 0–100 mm visual analogue scale (VAS) despite analgesics and non-steroidal anti-inflammatory drugs; at least three painful joints, Kellgren-Lawrence grade ≥2) were randomised to receive two infusions 4 weeks apart (weeks 0 and 4) of tocilizumab (8 mg/kg intravenous) or placebo. The primary endpoint was changed in VAS pain at week 6. Secondary outcomes included the number of painful and swollen joints, duration of morning stiffness, patients’ and physicians’ global assessment and function scores.ResultsOf 104 patients screened, 91 (45 to tocilizumab and 46 to placebo; 82% women; mean age 64.4 (SD 8.7) years) were randomly assigned and 79 completed the 12-week study visit. The mean change between baseline and week 6 on the VAS for pain (primary outcome) was −7.9 (SD 19.4) and −9.9 (SD 20.1) in the tocilizumab and placebo groups (p=0.7). The groups did not differ for any secondary outcomes at weeks 4, 6, 8 or 12. Overall, adverse events were slightly more frequent in the tocilizumab than placebo group.ConclusionTocilizumab was no more effective than placebo for pain relief in patients with hand osteoarthritis.

This review summarizes evidence relating to prophylaxis for gout flares after the initiation of urate-lowering therapy (ULT). We searched MEDLINE via PubMed for articles published in English from 1963 to 2013 using MEsH terms covering all aspects of prophylaxis for flares. Dispersion of monosodium urate crystals during the initial phase of deposit dissolution with ULT exposes the patient to an increased rate of acute flares that could contribute to poor treatment adherence. Slow titration of ULT might decrease the risk of flares. According to the most recent international recommendation, the two first-line options for prophylaxis are low-dose colchicine (0.5 mg once or twice a day) or low-dose NSAIDs such as naproxen 250 mg orally twice a day. They can be given for up to 6 months. If these drugs are contraindicated, not tolerated or ineffective, low-dose corticosteroids (prednisone or prednisolone) might be used. Recently, reports for four trials described the efficacy of canakinumab and rilonacept, two IL-1 inhibitors, for preventing flares during the initiation of allopurinol therapy. Prophylaxis for flares induced by ULT is an important consideration in gout management. Low-dose colchicine and low-dose NSAIDs are the recommended first-line therapies. Although no IL-1 blockers are approved as prophylactic treatment, this class of drug could become an interesting option for patients with gout with intolerance or contraindication to colchicine, NSAIDs or corticosteroids.

We lack strong evidence for an association between low SUA level and cognitive decline over time. Conversely, high SUA level might increase the cerebrovascular burden and the risk of vascular dementia; physicians should continue to treat hyperuricemia when appropriate.