December 2023 to March 2024
Author: Emre Bilgin & Rudi Shukla
Annals of Rheumatic Diseases
Aymon et al (doi: 10.1136/ard-2023-224670) compared treatment discontinuations for adverse events in a real world rheumatoid arthritis population (JAK-pot collaboration of registers) on second-line therapies. They reported that adjusted cause-specific hazard rate of treatment discontinuation for AEs was similar for TNFi versus JAKi (1.00, 95% CI 0.92 to 1.10) and higher for other modes of action versus JAKi (1.11, 95% CI 1.01 to 1.23), lower with TNFi compared with tofacitinib (0.81, 95% CI 0.71 to 0.90), but higher for TNFi versus baricitinib (1.15, 95% CI 1.01 to 1.30) and lower for TNFi versus JAKi in patients 65 or older with at least one cardiovascular risk factor (0.79, 95% CI 0.65 to 0.97).
Baker et al (doi: 10.1136/ard-2023-225445) investigated immunomodulatory mechanisms of anifrolumab in moderate to severe systemic lupus erythematosus (SLE) patients using longitudinal transcriptomic and proteomic analyses of the TULIP-1 and TULIP-2 trials. More than 2000 genes were modulated by anifrolumab by week 24 and 41 proteins by week 52. Anifrolumab downregulated multiple inflammatory pathways including type I and II interferon-induced gene pathways and type III type III IFN-λ protein levels.
Pitsigavdaki et al (doi: 10.1136/ard-2023-224919) assessed the validity of Definition of remission in SLE (DORIS) and Lupus Low Disease Activity State (LLDAS) in a cohort of 348 moderate-to-severe SLE with a median follow up of 5 years. They highlighted that sustained DORIS and LLDAS for ≥6 months resulted in reduced damage accrual (HR: 0.58; 95% CI 0.36 to 0.93 and 0.61; 0.43 to 0.86) and severe flares (HR: 0.14; 0.08 to 0.27 and 0.19; 0.13 to 0.27). Using a combination linear modelling and clustering they demonstrated patients with predominant arthritis and mucocutaneous disease experienced reduced DORIS/LLDAS compared to those with major organ involvement.
Gossec et al (doi: 10.1136/ard-2024-225531) provided the 2023 update on EULAR recommendations for the management of psoriatic arthritis (PsA) with pharmacological therapies. Main recommendations were that non-steroidal anti-inflammatory drugs should be used in monotherapy only for mild PsA in short term and oral glucocorticoids were not recommended. For peripheral arthritis, if target not achieved with conventional synthetic DMARDs, biologic DMARDs are recommended without any preference for mode of action. Algorithms are proposed for skin, axial or entheseal involvement.
Di Matteo et al (doi: 10.1136/ard-2023-225443) assess the discriminative value of Outcome Measures in Rheumatology (OMERACT) ultrasound lesions of enthesitis and their associations with clinical features in patients with spondyloarthritis. In univariate analyses, all OMERACT lesions of enthesitis (active inflammation and structural damage) except enthesophytes were significantly associated with SpA compared to controls whilst power Doppler (OR=8.77, 95% CI: 4.40 to 19.20) and bone erosions (OR=4.75, 95% CI: 2.43 to 10.10) retained this association in the multivariate analysis. Among the lower limb entheses, only the Achilles tendon was significantly associated with SpA (OR=9.20, 95% CI: 4.21 to 23.20).
Wu et al (doi: 10.1136/ard-2023-225284) investigated 701 retrospectively enrolled patients with anti-synthetase syndrome and reported that anti-Jo1, anti-PL7, anti-PL12 and anti-EJ antibody subtypes demonstrated no significant differences in incident of rapidly progressive interstitial lung disease (RP-ILD) or prognoses. Using machine-learning they further identified three endotypes – (1) RP-ILD cluster with high mortality, (2) dermatomyositis-like cluster with intermediate prognosis, (3) arthritis (and mechanic’s hands) cluster with good prognosis.
Fukui et al (doi: 10.1136/ard-2023-225389) used longitudinally collected annual medical examination data from 63,486 individuals in Japan over a 10-year period to explore whether changes in alcohol intake have a clinically relevant association with serum urate (SU) change. They reported that decreasing one daily alcohol intake had a clinically small association with SU changes [−0.019 (95% CI: −0.021 to –0.017) mg/dL]. Complete discontinuation of any alcohol from a mean of 1.o drinks/day was associated with [−0.110 mg/dL (95% CI: −0.154 to –0.066) decrease in serum urate in hyperuricemicparticipants.
Papadimitriou et al (doi: 10.1136/ard-2023-224827) conducted ex vivo analysis of affected skin and blood samples from 165 systemic sclerosis and 80 healthy individuals using single-cell transcriptomics, flow cytometry and multiplex immunofluorescence staining. They reported higher numbers of proliferating and cytotoxic T cells and Natural Killer cells in SSc-affected skin. These cells were also shown to selectively express CD7 in association with cytotoxic, proinflammatory and profibrotic genes, especially in recent onset and severe disease.
Lodka et al (doi: 10.1136/ard-2023-224875) used pre-clinical myeloperoxidase-anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitidies (MPO-AAV) mouse models with necrotizing crescentic glomerulonephritis (NCGN) to demonstrate that CD19-targeting chimeric antigen receptor (CAR) T cells efficiently depleted B cells including those that produced MPO-ANCA and protected from the development of NCGN compared to control CAR T cells.
De Valence et al (doi: 10.1136/ard-2023-224819) described serious infections and their risk factors in individuals with Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome using the multicentre French registry data. In 74 patients, The most common sites of infection were lung (59%), skin (10%) and urinary tract (9%). Sixteen percent severe infections occurred without any immunosuppression and with a daily glucocorticoid dose ≤10 mg. Age >75 years [HR (95% CI) 1.81 (1.02 to 3.24)], p.Met41Val mutation [2.29 (1.10 to 5.10)] and arthralgia [2.14 (1.18 to 3.52)] were associated with the risk of serious infections. Janus kinase inhibitors were most associated with serious infections compared to biologics and azacitidine.
Emre Bilgin
Emre is a rheumatologist at Hacettepe University where he is doing his MSc on epidemiology. His main interests are rheumatoid arthritis, adult Still’s disease and ANCA-associated vasculitis, aside from his enthusiasm for editorial activities. Emre is a member of the Social Media Sub-Committee.
Rudi Shukla
Rudi Shukla is a clinical research fellow at the Centre for Musculoskeletal Research, University of Manchester, UK and a rheumatology trainee at Health Education England North West, UK. His research interests include outcome measures in inflammatory arthritis, musculoskeletal ultrasound and omics analyses. Rudi is a member of the Social Media Sub-Committee.