Arthritis & Rheumatology最新文献

Introduction: Rheumatoid sarcopenia, characterized by the progressive loss of skeletal muscle mass and function, is a frequent comorbidity in rheumatoid arthritis (RA), linked to prolonged, severe systemic inflammation. Purinergic signaling (adenosine, AMP, and ATP) plays a crucial role in inflammation, myogenesis, and muscle hypertrophy. Dipyridamole, an antiplatelet agent, enhances extracellular adenosine availability, alters AMP/ATP ratio and activates A2BR and AMPK pathways. We aim to investigate its potential use as a therapeutic agent for RA and rheumatoid sarcopenia.

Methods: K/BxN-induced mice received preventive or therapeutic dipyridamole treatment daily and were sacrificed at joint inflammation peak and resolution stage. Motor activity tests and dual-energy x-ray absorptiometry (DXA) were performed. C-reactive protein (CRP) levels were also analyzed in serum and cytokines array was performed in serum and muscle. Histology of tibialis anterior (TA) and talus joint were studied. Myogenesis, purinergic system, atrophy and senescence key markers were analyzed via Western Blot and RT-PCR in gastrocnemius (GA). Nucleotide content via HPLC was performed. 2D and 3D models with C2C12 cells were done.

Results: Dipyridamole reduced joint, muscle, and systemic inflammation, counteracting muscle wasting and physical inactivity via an anabolic mechanism involving down-regulation of myostatin expression. This effect was mediated by increased adenosine and AMP levels, which activate adenosine A2B receptor and downstream cyclic AMP/AMPK signaling pathways.

Conclusion: These results support a dual role for dipyridamole in RA, combining robust anti-inflammatory effects with a novel, myostatin-linked anabolic action on sarcopenia, mediated through adenosine and AMPK signaling, distinct from conventional therapeutic mechanisms.

Objective: The multinational, phase 3, double-blind, placebo-controlled TULIP-SC trial evaluated the efficacy and safety of subcutaneous anifrolumab in adults who have moderate-to-severe SLE activity, despite receiving standard therapy.

Methods: Adults with SLE received subcutaneous anifrolumab 120 mg or placebo once weekly for 52 weeks (1:1 randomization). Only the primary endpoint (treatment difference in BILAG-based Composite Lupus Assessment [BICLA] response at 52 weeks) was formally tested in a pre-planned interim analysis; key secondary and other endpoints were tested in the full analysis.

Results: At the interim analysis (220 patients, anifrolumab: n=109; placebo: n=111), the primary endpoint was met (anifrolumab vs placebo: 59.4% vs 43.9%; BICLA response difference [95% confidence interval]=15.5% [2.3-28.6%], p=0.0211). The full analysis included 367 patients (anifrolumab: n=184; placebo: n=183). Versus placebo, more patients treated with anifrolumab attained a BICLA response whilst maintaining low/reduced oral glucocorticoid doses through Week 52 (56.2% vs 34.0%; difference=22.3% [12.3-32.2] p<0.0001), and the time to first sustained BICLA response was reduced (Hazard ratio=2.2 [1.5-3.2]; p<0.0001). Treatment differences in Week 52 DORIS remission and Low Lupus Disease Activity State attainment rates favored anifrolumab over placebo (14.2% [5.6-22.8%], p=0.0012, and 14.1% [4.6-23.6%], p=0.0038). The frequencies of serious adverse events were 11.9% with anifrolumab and 10.4% with placebo; the frequencies of herpes zoster were 3.8% and 1.1%, respectively.

Conclusion: Consistent with the well-established profile of intravenous anifrolumab, subcutaneous anifrolumab demonstrated significant, clinically meaningful treatment benefits when added to standard therapy, and an acceptable safety profile in patients with moderate to severe SLE.