Comparative 3-Year Safety Outcomes in Patients with Ankylosing Spondylitis Initiating JAK Inhibitor or TNF Inhibitor Therapy

Presenter: Hsin-Hua Chen

This retrospective cohort study compared safety outcomes in ankylosing spondylitis (AS) patients initiating Janus kinase inhibitors (JAKi) versus tumor necrosis factor inhibitors (TNFi), using matched cohorts (n=299 each) from the TriNetX network. 

Over a 3-year follow-up, JAKi use was linked to higher all-cause mortality (HR 4.94) and gastrointestinal bleeding, while malignancy occurred only in TNFi users. No significant differences were observed in cardiovascular events, venous thromboembolism, or serious infections. Herpes zoster incidence trended higher with JAKi. Neuropsychiatric outcomes were numerically lower with JAKi. These findings suggest distinct safety profiles, emphasizing the need for individualized treatment decisions in AS management.

JAK1 Selective Inhibitors versus Pan-JAK inhibitors: Comparative Real-world Study of Drug Retention in Chronic Inflammatory Arthritis 

Presenter:Leticia Leon

This retrospective study evaluated treatment retention in chronic inflammatory arthritis (CIA) patients—Rheumatoid Arthritis (RA), Psoriatic Arthritis (PsA), and Spondyloarthritis (SpA)—treated with Janus kinase inhibitors (JAKis) from 2017 to 2024. 

Among 227 treatment courses, pan-Janus kinase inhibitors (tofacitinib, baricitinib) had higher discontinuation rates than Janus kinase 1 (JAK1) selective inhibitors (upadacitinib, filgotinib). Discontinuation was mainly due to inefficacy (55%) and adverse events (42%). Higher risk was associated with female gender, PsA, cardiovascular comorbidities, and prior biologic or targeted synthetic disease-modifying antirheumatic drugs. These findings suggest JAKi class and patient characteristics significantly influence treatment retention in real-world CIA management.

Allogenic Anti- CD19 CAR-T Cells Induce Remission in Refractory Systemic Lupus Erythematosus

Presenter: Chunnei Yang

This investigator-initiated trial evaluated BRL-303, a healthy donor-derived, genome-edited allogeneic CD19-targeted chimeric antigen receptor T-cell (CAR-T) therapy, in four adults with refractory systemic lupus erythematosus (SLE). 

Following lymphodepletion (except one patient), BRL-303 infusion led to robust CAR-T expansion, sustained B-cell depletion, and clinical remission per Systemic Lupus International Collaborating Clinics (SLICC) criteria. All patients achieved SELENA-SLEDAI scores of zero and improved serologic markers. One patient attained drug-free remission; others required low-dose glucocorticoids. Only mild cytokine release syndrome occurred; no neurotoxicity or graft-versus-host disease was observed. BRL-303 demonstrated promising efficacy and safety, suggesting a potential paradigm shift in treating refractory SLE.

Combination Therapy with TNF Inhibitors and JAK Inhibitors in Multi-Drug-Resistant Rheumatoid Arthritis: A Case Series from the RA UCLouvain Brussels Cohort

Presenter: Francesco NATALUCCI

Rheumatoid Arthritis (RA) is a chronic autoimmune disease; 20–40% of patients fail to achieve remission with bDMARDs and tsDMARDs, and a subset (MDR-RA) remains refractory. A descriptive study of five patients (3F, 2M) from the UCLouvain Brussels Cohort explored TNFi + JAKi combination therapy after a median of 184 months (IQR 116) from diagnosis. 

All were refractory to 7 bDMARDs and 2 JAKi. No major adverse events occurred. Three patients showed clinical improvement; one achieved sustained remission for 3 years. The combination therapy showed promise in MDR-RA with good tolerability, especially in younger patients with low infection risk.

Combination of ­TNF Inhibitors and NSAIDs versus ­TNF Inhibitors Alone on the Progression of Structural Damage in the Spine and Hip: A Retrospective Study in 262 Patients with Radiographic Axial Spondyloarthritis

Presenter: MARIA KONSTA

This study assessed whether adding NSAIDs to TNFi therapy in 262 r-axSpA patients (189 men; age 44±12 years; disease duration 7.3 years, IQR: 2–15) improves radiographic outcomes. 

After 2.5±0.7 and 7±2.3 years, spinal progression was lower in the TNFi+NSAIDs group (ΔmSASSS/year: 0.1 vs. 0.7; p=0.0009). New syndesmophytes occurred in 36% with combination therapy vs. 58% with TNFi alone (p=0.001). Hip damage (BASRI-hip, MJSW) remained unchanged, regardless of NSAIDs use. NSAIDs co-administration showed a protective effect on spinal progression but not on hip structural damage, likely due to differing pathophysiology in axial vs. peripheral joints.

Cardiovascular Outcomes in Diabetic Rheumatoid Arthritis Patients: TNF-α Inhibitors versus IL-6 Inhibitors

Presenter:Sila Mateo Faxas

A retrospective study assessed cardiovascular outcomes of IL-6 inhibitors (IL-6i) versus TNF-α inhibitors (TNFi) in 3158 rheumatoid arthritis (RA) patients with type 2 diabetes mellitus (T2DM), followed over five years.

IL-6i were linked to significantly higher risks of mortality (HR 1.626), heart failure (HR 1.399) and acute kidney failure (HR 1.772) versus TNFi. IL-6i were also associated with increased risks of arrhythmias (HR 1.459), pulmonary embolism (HR 2.092), and cardiac device-related infections (HR 3.485). Conversely, TNFi were linked to more diabetes-related follow-up visits. Hence, TNFi offered better cardiovascular safety in RA patients with T2DM, emphasizing the need to consider comorbid risks in treatment decisions.

Real-World Characteristics and Treatment Patterns of Difficult-to-Treat Psoriatic Arthritis

Presenter: Milad Heydari-Kamjani

A large retrospective study compared the manifestations and treatment patterns of difficult to treat (D2T) and non-D2T psoriatic arthritis (n=7,403). 

In comparison to non-D2T, D2T patients had higher body mass index (p<0.001), C- reactive protein levels (p<0.001), Crohn’s disease (p=0.045), and HLA-B27 positivity (p=0.005). They showed significantly higher use of biologic and targeted synthetic disease-modifying antirheumatic drugs (>4 in nearly half of the patients), including tumor necrosis factor inhibitors (adalimumab), interleukin (IL)-17 inhibitors (secukinumab), IL-23 inhibitors (guselkumab), IL-12/23 inhibitors (ustekinumab), Janus kinase inhibitors (tofacitinib), and tyrosine kinase inhibitors (deucravacitinib). These findings underscore the need for tailored therapeutic strategies.

Target Trial Emulation of Biologic and Targeted Synthetic Disease-Modifying Antirheumatic Drugs in Rheumatoid Arthritis-Associated Interstitial Lung Disease

Presenter: Gregory McDermott

A nationwide study in RA-ILD patients (n=2,716) compared rituximab with biologic and targeted synthetic disease-modifying antirheumatic drugs like abatacept, tocilizumab, JAK inhibitors, and TNF inhibitors.

No significant differences were found in the composite outcome of respiratory hospitalization, lung transplant, or death across treatment groups (abatacept HR 0.88, JAK inhibitor HR 0.75, tocilizumab HR 1.03, or TNF inhibitor HR 1.01, each versus rituximab). Abatacept and JAK inhibitors showed nonsignificant trends toward lower mortality versus rituximab. These findings challenged the 2023 ACR/CHEST guideline’s conditional recommendation of rituximab as first-line therapy and underscored the need for randomized controlled trials to guide RA-ILD treatment decisions.

Effectiveness of Nintedanib Combined with Different DMARDs in Joint and Pulmonary Domains of Rheumatoid Arthritis – Interstitial Lung Disease. National Multicenter Study of 74 Patients

Presenter: Ana Serrano-Combarro

The National Spanish multicenter study determined the progression of joint and pulmonary outcomes in 74 RA-ILD patients with PPF treated of nintedanib and DMARDs. Nintedanib was combined with bDMARDs (n=47, 33 abatacept, 10 rituximab); or with sDMARDs (n=29, 7 leflunomide, 6 methotrexate, 4 JAK inhibitor, 8 mycophenolate, 2 hydroxychloroquine, 1 azathioprine and 1 cyclophosphamide); or with both bDMARDs and sDMARDs (n=9); or was given as monotherapy (only glucocorticoids; n=13).

Median ILD duration before nintedanib was 51 months. At 12 months, nintedanib combined with either bDMARDs or sDMARDs effectively controlled joint activity in 81% of cases (87% with bDMARDs, 83% with sDMARDs; p=0.82). No significant decline in FVC or DLCO was observed over 12 months, with similar pulmonary outcomes across treatment groups. Amongst RA-ILD patients with PPF treated with nintedanib, articular inflammation could be managed either with bDMARDs or sDMARDs, with similar pulmonary function evolution.

Impact of Biologic Therapies on Cardiovascular and Venous Thromboembolic Events in Psoriatic Arthritis: Real-World Evidence

Presenter: Milad Heydari-Kamjani

This retrospective cohort study compared the risk of MACE and VTE among PSA patients treated with IL-17, IL-12/23, and IL-23 vs. those treated with anti-TNF agents.

In the cohort of 28,973 PsA patients (mean age 52.2; 56% female), IL-17 and IL-23 inhibitors were associated with significantly lower odds of MACE and VTE compared to anti-TNF agents. IL-17 inhibitors reduced risk of DVT (OR 0.58), PE (OR 0.45), MI (OR 0.50), and stroke (OR 0.56; all p<0.001). IL-23 inhibitors showed similar reductions: DVT (OR 0.49, p=0.02), PE (OR 0.12, p=0.005), MI (OR 0.29, p<0.001), stroke (OR 0.35, p=0.002). IL-12/23 inhibitors increased stroke risk (OR 1.41, p=0.04) without significant benefit for other outcomes. These findings support IL-17 and IL-23 inhibitors as safer cardiovascular options in PsA.

ACR 2025, 24th-29th Oct 2025, Chicago, Illinois, USA