Arthritis & Rheumatology最新文献

Background: Transition from long-term denosumab to PTH-analogs or romosozumab might expose patients to the risk of the so-called rebound phenomenon. Adding romosozumab to denosumab might represent an option in patients experiencing a fracture while on denosumab. The aim of this study was to investigate the effects of the combination of romosozumab to denosumab in post-menopausal osteoporosis.

Methods: We did a 36-month combined retrospective and prospective study analyzed with prospective score matching. Post-menopausal women were divided into two groups: patients on denosumab who added romosozumab to denosumab (Dmab from M-24 to M0 ➔ Dmab+Romo from M0 to M+12), and matched controls on denosumab continuing denosumab (Dmab from M-24 to M0 ➔ Dmab from M0 to M+12). Bone mineral density (BMD) and bone turnover markers (CTX, P1nP) were assessed at follow-up time points.

Results: A total of 50 women were included in the study. Twenty-five patients in the Dmab ➔ Dmab+Romo group and 25 matched controls in the Dmab ➔ Dmab group. The between-group difference at M+12 was 3.3% (95% CI -5.2-11.8), indicating a non-significant trend toward greater improvement with combination therapy. Adding romosozumab to denosumab increased P1nP significantly between M0 and M+3 (+22.5 ng/mL SE 8.7, p 0.028).

Conclusion: Ongoing treatment with denosumab did not blunt the anabolic response of romosozumab, indicating sustained modeling-based bone formation activity. Adding romosozumab in patients failing denosumab might be a valuable option.

Objective: Despite the availability of biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) to treat rheumatoid arthritis (RA), many patients do not experience optimized disease control. Glucocorticoids are effective but have safety risks. ABBV-154, an antibody-drug conjugate, is made up of adalimumab linked to a glucocorticoid receptor modulator. This phase 2b study evaluated the efficacy and safety of ABBV-154 in patients with moderately to severely active RA receiving background methotrexate with inadequate response to at least one prior b/tsDMARD.

Methods: Patients were randomized 1:1:1:1:1 to subcutaneous ABBV-154 40, 150, or 340 mg every other week; 340 mg every 4 weeks; or placebo. The primary endpoint was achieving 50% improvement in the American College of Rheumatology response criteria (ACR50) at week 12; secondary endpoints included achieving the ACR20 and ACR70 criteria. Treatment-emergent adverse events (TEAEs) were monitored. Clinical development of ABBV-154 was discontinued; the study was terminated early.

Results: Overall, 472 patients were treated. At week 12, more patients achieved ACR50 (primary endpoint) with ABBV-154 (25.5%-44.4% across dose groups) versus placebo (6.3%; all P < 0.001). ACR20 response rates were higher in all ABBV-154 treatment groups versus placebo (P < 0.001). Most ABBV-154 groups achieved the other secondary endpoints. For all ABBV-154 doses, TEAEs rates through week 12 were similar to placebo. Ten serious infection TEAEs occurred in the ABBV-154 groups.

Conclusion: ABBV-154 demonstrated superior efficacy over placebo in patients with RA and inadequate response to prior b/tsDMARDs. TEAE rates in all ABBV-154 arms were comparable with placebo. These findings provide useful insights into the design of new antibody-drug conjugates for RA.

Efferocytosis, the process through which phagocytes clear apoptotic cells (ACs), has rapidly emerged as an expanding field of research. This multistep process involves recognizing, binding, internalizing, and degrading ACs. Efferocytosis clears ACs, preventing their secondary necrosis, generating anti-inflammatory mediators, and promoting the resolution of inflammation. Appropriate efferocytosis is essential for preserving immune tolerance and preventing exposure to self-antigens, whereas defective efferocytosis is linked to the onset of various rheumatic diseases. Here, we review the process of efferocytosis and its implications in common rheumatic diseases. This review focuses on the role of abnormal efferocytosis in the development and progression of systemic lupus erythematosus. We also summarize recent advances in understanding efferocytosis in other rheumatic diseases, including rheumatoid arthritis (RA), Sjögren disease, antineutrophil cytoplasmic antibody-associated vasculitis, systemic sclerosis, antiphospholipid syndrome, gout, and osteoarthritis. Notably, a clinical trial investigating AC infusion for refractory RA has been proposed, highlighting the therapeutic potential of targeting efferocytosis. In addition, emerging strategies-such as liver X receptor/peroxisome proliferator-activated receptor agonists; DNase-containing nanoparticles; Tyro3, Axl, and Mer receptor agonists; and anti-CD47 antibodies-show promise, although most remain at the preclinical stage. Despite the challenges posed by the immune system's complexity and the pleiotropic functions of efferocytosis-related molecules, growing evidence supports efferocytosis as a potential therapeutic target in rheumatic diseases.