Autumn 2025 Press Review – Miscellanous

April 2025 to July 2025

Author: Victoria Konzett

Upadacitinib FDA and EMA-approved for treatment of giant cell arteritis after positive results from the SELECT-GCA study

Blockmans et al. (10.1056/NEJMoa2413449) compared Upadacitinib 15mg daily and 7.5mg daily combined with a 26-week glucocorticoid taper with placebo combined with a 52-week glucocorticoid taper in 428 patients above 50 years of age, with new-onset or relapsing giant cell arteritis, in the double-blind, randomized, phase 3 SELECT-GCA trial. Upadacitinib 15 mg, but not 7.5mg, combined with a 26-week glucocorticoid taper significantly improved sustained remission rates through weeks 12 to 52 and reduced disease flares and steroid exposure in this study. Safety was comparable between groups. Serious infections were numerically higher in the placebo arms, while Upadacitinib showed increased rates of herpes zoster infections, non-melanoma skin cancers and non-pathologic Creatine kinase elevations. No major cardiovascular events were observed in the upadacitinib arms.

Methotrexate as a viable alternative to glucocorticoids as first-line treatment  in pulmonary sarcoidosis

Kahlmann et al. (10.1056/NEJMoa2501443) compared methotrexate  with prednisone – the currently recommended first-line treatment for pulmonary sarcoidosis – in the multicenter, open-label, randomized, non-inferiority PREDMETH trial. In 138 patients with previously untreated pulmonary sarcoidosis methotrexate (15 mg per week increased by 5 mg every 4 weeks to a maximum dose of 25 mg per week if tolerated) was noninferior to prednisone for improving lung function over 24 weeks. Unadjusted mean change from baseline to week 24 in the percentage of the predicted forced vital capacity was 6.75 percentage points (95% CI 4.50 to 8.99) in the prednisone group and 6.11 percentage points (95% CI 3.72 to 8.50) in the methotrexate group (∆ −1.17 percentage points, 95% CI −4.27 to 1.93). Adverse event rates were comparable, but profiles differed: prednisone caused more weight gain, insomnia and increased appetite, while methotrexate led to more nausea, fatigue, and abnormal liver function tests.

Passive maternal immunity in children born to women with systemic autoimmune rheumatic diseases compared to healthy women

Mazzucato-Puchner et al. (10.1016/j.jaut.2025.103439) compared antibody titers in venous blood samples and umbilical cord blood in a case-control study of 25 pregnant women with systemic autoimmune rheumatic diseases (SARD) and 30 healthy controls. An effective transplacental transfer of existing antibodies against varicella-zoster and rubella, as well as newly generated antibodies against SARS-CoV-2 after vaccination during pregnancy could be observed both in the SARDs and the control group. This suggests a robust passive immunity in newborns to women with SARDs, including those receiving immunosuppressive therapy (hydroxychloroquine, azathioprine, TNF inhibitors, salazopyrine) during pregnancy.

Low-dose methotrexate failed to show relevant benefits on signs and symptoms of inflammatory knee osteoarthritis in a placebo-controlled trial

Zhu et al. (10.1001/jamainternmed.2025.1359) investigated the use of low-dose methotrexate for treatment of inflammatory knee osteoarthritis, in a multicenter, randomised, placebo-controlled trial of 215 patients with effusion synovitis due to osteoarthritis on MRI from China. Patients started methotrexate at 5mg weekly for two weeks and increased to up to 15mg weekly throughout to trial if tolerated. This strategy did not significantly improve knee pain or reduce effusion-synovitis over 52 weeks compared to placebo, and no meaningful effect was seen on secondary outcomes either. Adverse event rates were similar between groups. Methotrexate can not therefore not be supported for symptom relief or disease modification in inflammatory knee osteoarthritis.

Allogeneic CD19-targeting T cells induced clinical remission in four of five patients with refractory systemic lupus erythematosus (SLE) and lupus nephritis

Wang et al. (10.1038/s41591-025-03899-x) investigated  YTS109, a hypo-immune allogeneic CD-19 targeting T cell product engineered using CRISPR–Cas9 to knock out TRAC, PD1, HLA-A, HLA-B and CIITA, in a phase 1 study in five patients with severe, refractory SLE and complicating lupus nephritis. The compound was well-tolerated, with only mild cytokine release symptoms on no graft-versus-host reactions observed. All five patients achieved SLE responder index 4 response at M3, and four of five patients showed a rapid and sustained reduction in SLE disease activity score (mean 31.30–5.35 by M6), while one patient flared at M6. Resolution of inflammation and tissue restoration was seen in renal biopsies.