Last week, Barcelona hosted the 2025 EULAR (European Alliance of Associations for Rheumatology) Congress. From 11-14 June, presentations and discussions highlighted advancements in the rheumatology space, addressing key pipeline updates, clinical practice recommendations, and innovative thinking in areas such as artificial intelligence (AI) and digital therapeutics.
This year’s event was a large one, with a full programme of scientific sessions, poster presentations, and more; while we can’t promise a comprehensive overview in a single article, we can explore some key highlights.
Increasing Focus on Multi-System Diseases
At the conference, I noted an increasing interdisciplinary focus, recognising the fact that rheumatologists treat multi-system diseases and frequently need to make or collaborate on treatment decisions across skin, pulmonary, kidney, and other manifestations. Sessions covered both a multidisciplinary approach to key diseases—such as inflammatory myopathies—as well as specific specialties, such as dermatology, ophthalmology, and nephrology.
This linked to a focus across manifestations of systemic immune-mediated diseases, particularly exemplified by Boehringer Ingelheim (BI) and their approach for the small-molecule PDE4B inhibitor, nerandomilast. A subgroup analysis from BI’s FIBRONEER-ILD PPF trial in patients with interstitial lung disease (ILD) associated with autoimmune and rheumatic diseases—including rheumatoid arthritis (RA), systemic sclerosis (SSc), myositis, Sjögren’s disease, and others—showed a relative reduction in change in forced vital capacity (FVC) vs. placebo of 39-43%. It also showed a reduced risk of acute exacerbations and death.
Those positive signals have led to a specific trial (FIBRONEER-SARD) focused on systemic autoimmune rheumatic disease-associated interstitial lung disease (SARD-ILD) with background immunosuppression. It will include key secondary endpoints such as CRISS (Combined Response Index for Systemic Sclerosis) to assess impact beyond the lungs. If successful, the asset could be transformational across multiple systemic diseases, including in future highly competitive markets like systemic sclerosis.
Implications:
It will become even more important for companies to widen their focus beyond the musculoskeletal system in the evolving landscape. In multi-system inflammatory diseases where rheumatologists lead treatment, there are going to be more treatment options that address the lungs, skin, vascular, and renal organs and more, providing one treatment option for complex diseases rather than many that treat individual symptoms. Market builders will also need to consider rheumatologist disease awareness across organ systems, alongside engaging with other specialties.
Guidance for Defining Difficult-to-Manage and Treatment-Refractory Psoriatic Arthritis (PsA)
EULAR also provided points to consider for defining difficult-to-manage and treatment-refractory psoriatic arthritis. The goal is to move from a wide range of definitions—and therefore heterogeneous epidemiology and data for these high-unmet need patients—to a consensus that could provide guidance for future trials. The definitions presented focused on:
- Failure to achieve or maintain response to ≥2 bDMARDS or tsDMARDs (biologic or targeted synthetic disease-modifying anti-rheumatic drugs) with ≥2 mechanisms of action
- Ongoing patient or rheumatologist dissatisfaction with treatment, and
- Evidence of persistent disease
For treatment-refractory PsA, other causes of persistent disease (e.g. comorbidities, psychosocial factors) also need to be ruled out.
Implications:
These points to consider provide helpful guidance for companies initiating trials in these two patient populations. Companies should also consider building a deeper understanding of the reasons for poor treatment response and patient endotypes (e.g., via including tissue samples and deep imaging in trial designs) to move towards precision medicine in PsA.
New Data to Support Early Treatment of PsA and Rheumatoid Arthritis (RA)
At the other end of the treatment spectrum, new data encouraged early treatment in PsA, RA, and other diseases. Multiple presentations demonstrated the advantage of early combination DMARD treatment and/or treat-to-target strategies in PsA, and similar findings in RA. One study noted that first-line anti-TNF therapy in early RA was linked to lower likelihood of difficult-to-treat disease at 5 years. Even pre-RA diagnosis, a study was presented in palindromic rheumatism, which progresses to RA in up to 66% of patients. It showed that the likelihood of developing rheumatoid arthritis and time to diagnosis was significantly lower for patients treated with abatacept vs. the standard of care hydroxychloroquine, with only 9% of patients developing RA after 2 years vs. 28% for hydroxychloroquine.
Implications:
The case continues to build for treating early and robustly to aim for resolution of inflammation or remission – ideally preventing the development of a severe disease like RA at all. There is significant opportunity for new therapies to target this early patient population, although providing a compelling proposition for payers will be key for success.
Progress in Underserved Diseases Alongside a Ramp-Up in Competition in Strong Markets
We saw new data and progress in development across diseases, notably in lupus, both systemic lupus erythematosus (SLE) and lupus nephritis (LN). At past EULAR congresses, the conversations had been on trial recruitment, given the large number of late-stage trials competing for a relatively small patient population, but many trials are progressing now and will hopefully bring new therapeutic options to market.
Key data included phase 2 SLE data for Merck’s enpatoran (TLR7/8i), which had showed a significant reduction in CLASI-A scores at week 16 vs. placebo for cutaneous and systemic lupus (CLE / SLE) patients with predominant skin activity. However, the week 24 BICLA (BILAG-Based Composite Lupus Assessment) data did not meet the primary endpoint due to a lack of dose response. A positive signal was seen for the 25 mg dose, particularly in patients receiving glucocorticoids and those with high IFN-GS levels at baseline. Regulatory discussions are upcoming, as reported by the company.
New data from the phase 3 trial for dapirolizumab pegol (CD40Li, Biogen / UCB), which met the primary endpoint of significant improvement in BICLA, analysed rates of achievement of low disease activity (LLDAS) or remission (DORIS), as recommended by EULAR. The data found significant improvement across both metrics, both higher rates of achievement and maintenance over a longer time vs. placebo.
AbbVie’s combination of the BTKi elsubrutinib and the JAKi upadacitinib, ABBV-599, showed maintenance of response to 2 years. Cabaletta Bio’s Rese-cel autologous CAR-T therapy demonstrated proof of concept in three of four non-renal SLE patients who achieved DORIS remission without immunomodulators or glucocorticoids. While these are promising results for a new treatment modality in immunology, more data will be needed to assess the efficacy in lupus nephritis patients, also included in the trial, and to expand efficacy data to a larger sample.
Outside of lupus, new data was also presented for currently marketed therapies, such as
- 3-year efficacy and safety of Bimzelx in PsA and axial spondyloarthritis (axSpA) with 2-year inhibition of structural progression
- Tremfya inhibition of structural progression in PsA to week 24
- Rinvoq 7-year RA and 5-year PsA data and safety analysis across the SELECT programme, indicating potential generally similar safety to adalimumab and methotrexate across 17,000 patient-years
- POETYK trial PsA data that may support registration of Sotyktu for PsA demonstrating potential for another oral option
Data presented for pipeline competitors included MoonLake’s sonelokimab (IL-17A/F; phase 2, 24-week PsA data) and Takeda’s TAK-279 (TYK2i; phase 2b PsA data), alongside a review of B-cell depletory evidence including Amgen’s dazodalidep (CD40/40L; Sjögren’s disease) and RemeGen’s telitacicept (BAFF / APRIL; SLE and Sjögren’s disease globally), amongst other mechanisms of action.
Implications:
Competition across rheumatology is increasing and will continue to do so. Companies will need to find differentiation strategies in crowded markets with high barriers to entry, like RA and PsA. In lupus, the market is moving from two biologics to many with a wave of launches over the next few years. Strong launch execution, competitive strategy, and clear patient targeting to match the best treatment to the right patient will be key.
CAR-T Therapies Show Early Potential
Excitement about CAR-T data also included two other potential patient populations for Cabaletta Bio’s Rese-cel, immune-mediated myopathies and systemic sclerosis. Early data in dermatomyositis (DM), antisynthetase syndrome (ASyS), and diffuse cutaneous systemic sclerosis (dcSSc) showed potential, with TIS observed in 3 of 4 treated DM and ASyS patients and mRSS decrease with FVC increase observed in 2 dcSSc patients.
Cabaletta is targeting BLA submission in myositis, or subpopulations within myositis, in 2027. They are planning FDA registrational discussions in systemic sclerosis later this year.
A phase 1 study of CAR-Treg cells targeting citrullinated proteins in the synovia of patients with refractory RA is in the early stages of proof of mechanism. The study has showed in a single patient that the engineered Treg cells maintained ability to home to inflamed tissue. There was also case data presented for an allogeneic CD19 CAR-NK treatment in SLE, which could provide a different approach.
Implications:
CAR therapies are showing early potential in inflammatory diseases, with opportunity to reset inflammation and be transformative for patients. They could prove to be best-in-class B-cell depleters, which potential competitors will need to consider; incremental benefit vs. 1st-generation B-cell depleters such as rituximab will need to be established for broad use at the anticipated price tag. However, there is potential beyond B-cell depletion, with opportunity to provide multiple therapeutic options for patients.
B-Cell Depletion Beyond CAR-Ts, Plus the Rise of Artificial Intelligence
In new therapeutic modalities beyond CAR-Ts, B-cell depletion continues to be a major focus. Novartis’ ianalumab, an inhibitor of BAFF-R and driver of B-cell depletion via antibody-dependent cellular cytotoxicity (ADCC), demonstrated significant reduction in disease activity in Sjögren’s disease and SLE in phase 2 trials. It has now progressed to phase 3, also in lupus nephritis. Novartis is targeting approval in 2026.
Much earlier in the pipeline, promising preclinical data was presented for a bispecific (TRBV9, CD3) T-cell engager targeting depletion of the TRBV9+ T-cell compartment in ankylosing spondylitis and Crohn’s disease, which showed activity in preclinical assays. Data was also presented for CytoCares’s trispecific (CD19, CD3, CD28) T-cell engager CC312, and a basket investigator-initiated study is ongoing.
Artificial Intelligence (AI) is also driving new treatments. Axia, a digital therapeutic for axSpA that offers a patient-tailored exercise program, showed significant improvements in BASDAI, BASFI, and ASQoL. The research team expanded their analysis based on those positive results to show significant improvement in ASAS20 and ASAS40.
Even if digital therapeutics are adopted broadly in the future, an unmet need for pharmacologic treatments is likely to remain, particularly given that patients in the Axia trial needed a relatively high baseline activity level, potentially limiting use to milder axSpA patients.
A broader discussion on the use of AI in rheumatology highlighted the potential, particularly for diagnosis, biomarker discovery, and clinical decision-making via predictive modelling. The discussion also acknowledged patient concerns regarding the ultimate responsibility of a doctor for their care, data privacy, and the need for consent and education when AI is being used. Healthcare providers have been slow to adopt digital technologies overall, primarily due to system integration challenges and lack of training on how to use it.
Implications:
There is exciting potential for AI in rheumatological disease diagnosis and treatment, with a potential link to earlier diagnosis and treatment, better long-term outcomes, and the potential for remission. However, there are key barriers that companies in the space will need to overcome. They will need to engage across the care continuum to ensure that solutions address all relevant needs and concerns.
Looking Ahead…
Blue Matter will continue to publish resources related to inflammatory diseases and markets—as well as a host of other therapeutic areas—as we move into the second half of 2025. To stay up to date on our latest publications, please follow us on LinkedIn or check our Insights page regularly.
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