Spring 2025 Press Review – Annals of Rheumatic Diseases

December 2024 to March 2025

Author: Victoria Konzett & Mustafa Ekici

Risk of developing psoriatic arthritis in patients with psoriasis initiating treatment with different classes of biologics

Gisondi P, et al. (doi:10.1016/j.ard.2025.01.006) compared the risk of arthritis development in psoriasis patients starting three biological therapies (TNFi, IL-17i, or IL-23i). In a total of 622 patients, 60 (10%) developed arthritis within a mean follow-up time of 4.1 (±2.1) years (2,510 patient years of follow-up). Inverse probability-weighted hazard ratios for arthritis development were 0.63 (95% CI, 0.38-1.05) for IL-17i and 0.57 (95% CI, 0.34-0.96) for IL-23i, when compared with the TNFi group.

Multiorgan involvement and circulating IgG1 predict hypocomplementaemia in IgG4-related disease

Katz G, et al. (doi:10.1136/ard-2024-225846) investigated factors associated with hypocomplementaemia in IgG4-related disease (IgG4-RD). Among 279 patients, hypocomplementaemia was observed in 32% and was linked to multiorgan involvement, particularly lymph node (OR 2.59) and lung (OR 2.56) involvement. Fibrotic manifestations and lacrimal gland involvement were inversely associated. Elevated IgG1 levels, but not IgG4, independently predicted hypocomplementaemia. These findings suggest that hypocomplementaemia reflects disease extent and that complement activation, driven by IgG1, plays a role in IgG4-RD pathophysiology.

Relationship between serum urate and changes in dual-energy CT monosodium urate crystal volume over 1 year in people with gout: an individual participant data analysis

Kelly B, et al. (10.1136/ard-2024-226059) examined the relationship between serum urate levels and changes in monosodium urate (MSU) crystal volume over 1 year in people with gout. Using dual-energy CT (DECT) scans, the study found that MSU crystal dissolution occurred at serum urate levels below 0.24 mmol/L, while crystal formation was observed at levels ≥0.48 mmol/L. Reductions in DECT urate volume were noted at serum urate levels below 0.42 mmol/L, whereas increased volumes occurred above 0.48 mmol/L. These findings suggest that maintaining serum urate below 0.24 mmol/L may promote crystal dissolution in gout. 

CD-19 CAR-T cells for polyrefractory rheumatoid arthritis

Lidar M, et al. (doi:10.1136/ard-2024-226437) tested autologous CD19 CAR-T cell therapy with CD28-costiumlation in a 39-year-old female patient with erosive RA refractory to nearly all available biological and targeted synthetic DMARDs. Synovial biopsy showed a high abundance of CD19+ B-cell despite all prior B-cell depleting therapies. After an initial period of severe side effects (cytokine release syndrome and neurotoxicity that required treatment with Tocilizumab, Anakinra and high-dose steroids), a significant drop in autoantibody levels and disease activity was observed, and drug-free remission was achieved within 100 days. This is the first reported case of CAR-T therapy in highly refractory RA, showing benefits but also risks of the novel therapeutic approach.

Ivarmacitinib, a selective Janus kinase 1 inhibitor, in patients with moderate-to-severe active rheumatoid arthritis and inadequate response to conventional synthetic DMARDs: results from a phase III randomised clinical trial

A new JAK1 selective inhibitor demonstrated significant benefits on signs and symptoms of RA in a phase 3 study from China, published by Liu J, et al. (doi:10.1136/ard-2024-226385). 599 RA patients with insufficient response to csDMARDs were randomized to Placebo, Ivarmacitinib 4mg once daily and Ivarmacitinib 8mg once daily. ACR20 response rates at week 24 were high overall, and significantly better in both treatment arms when compared with placebo (40.4% vs 70.4% and 75.1%, respectively).

Comparison of two strategies of glucocorticoid withdrawal in patients with rheumatoid arthritis in low disease activity (STAR): a randomised, placebo- controlled, double-blind trial

Ruyssen-Witrand A, et al. (doi:10.1136/ard-2024-226620) compared two glucocorticoid (GC) withdrawal strategies in rheumatoid arthritis (RA) patients with low disease activity (LDA): hydrocortisone replacement (20 mg/day for 3 months, then 10 mg/day for 3 months before discontinuation) and prednisone tapering (1 mg/month until discontinuation). At 12 months, GC discontinuation rates were similar (55% vs. 47%, p=0.4), with no significant differences in flares, disease activity, or patient-reported outcomes. Both strategies were safe, with no cases of acute adrenal insufficiency. The study concluded that hydrocortisone replacement offers no advantage over prednisone tapering for GC withdrawal in RA patients in LDA.

2024 EULAR points to consider on the initiation of targeted therapies in patients with inflammatory arthritis and a history of cancer

Sebbag E, et al. (doi:10.1136/ard-2024-225982) published the 2024 EULAR points to consider on the initiation of targeted therapies in RMD patients with a history of cancer. While prior malignancies are no contraindication for DMARD therapy, benefits and risks of both DMARD therapy and the untreated condition need to be balanced, considering also cancer type and time in remission. JAKi and Abatacept should be used with caution, TNFi may be preferred in case of solid cancers, and B-cell depletion preferred in case of lymphoma.

Efficacy and safety of infliximab or adalimumab in severe mucocutaneous Behçet’s syndrome refractory to traditional immunosuppressants: a 6-month, multicentre, randomised controlled, prospective, parallel group, single-blind trial

Talarico R, et al. (doi:10.1136/ard-2024-226113) assessed the efficacy of Adalimumab and Infliximab in 40 adult patients with active Behçet’s syndrome despite prior treatment with Azathioprine or Cyclosporine. Both treatment showed good clinical response rates (remission of mucocutaneous involvement; 64% in the IFX group 94% in the ADA group), and improvements in health-related quality of life, as well as good tolerability and drug retention, indication that TNFi is a viable mode of action for treatment of Behçet’s disease.

Precise identification and tracking of HMGCR-reactive CD4+ T cells in the target tissue of patients with anti-HMGCR immune-mediated necrotising myopathy

Tiniakou E, et al. (doi:10.1136/ard-2024-225732) identified the presence of Anti-3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) CD4-positive T-cells in patients with anti-HMGCR immune-mediated necrotizing myopathy (IMNM). The authors stimulated peripheral blood mononuclear cells (PBMCs) of IMNM and dermatomyositis (DM) patients with HMGCR proteins, and assessed CD4-activation via CD154 upregulation in flow cytometry analyses. T-cell responses were higher in IMNM patients than in DM patients, and correlated with anti-HMGCR antibody levels.

CD19-CAR T-cell therapy induces deep tissue depletion of B cells

Tur C, et al. (doi:10.1136/ard-2024-226142) demonstrated the distinct effects of CD19-CAR T-cell therapy versus rituximab (RTX) in autoimmune diseases (AIDs). In CD19-CAR T-treated patients, lymph node biopsies showed complete depletion of CD19+ and CD20+ B cells, disruption of follicular structures, and loss of follicular dendritic cells (FDCs). In contrast, RTX-treated patients exhibited B-cell depletion in peripheral blood but retained lymph node B cells, intact follicular structures, and preserved FDCs. Non-lymphoid tissues in CAR T-treated patients were also fully depleted of B cells. These findings highlight the superior and deeper tissue B-cell depletion achieved with CD19-CAR T-cell therapy, supporting its potential for long-term remission in AIDs.