Abstract
Rheumatology in 2025–2026 continued a measurable shift from disease-label–driven prescribing toward mechanism-centric, multi-indication immunology, as highlighted by the view that shared immune pathways enable therapies to be applied across diseases and that the future is increasingly “indication-agnostic and mechanism-centric.”[1] In parallel, a “remission-oriented future” was repeatedly framed around cellular and gene therapies, with CAR-T programs reporting immune reset and drug-free remission signals across systemic lupus erythematosus (SLE), myositis, and systemic sclerosis (SSc).[1–3] On the more immediate clinical horizon, long-term and real-world datasets clarified benefit–risk tradeoffs for targeted synthetic DMARDs (notably JAK inhibitors) in rheumatoid arthritis (RA) and supported explicit guideline language on tapering strategies and safety-informed sequencing.[4–6] For SLE and lupus nephritis (LN), EULAR’s 2025 kidney-involvement update operationalized biopsy-based diagnosis, time-bound response targets, and early combination regimens, while late-stage 2026 data supported expansion of B-cell–directed biologics and easier outpatient delivery of interferon pathway blockade (anifrolumab SC autoinjector).[7–10] Across spondyloarthritis, treat-to-target strategies were strengthened by early intensive therapy in psoriatic arthritis (PsA), while AI-enabled diagnostics and digital therapeutics emerged as clinically tested adjuncts in axial spondyloarthritis (axSpA).[11] Gout advances emphasized treat-to-target timing and next-generation URAT1 inhibition alongside new care models such as nurse-led home monitoring.[12, 13]
Introduction
The 2025–2026 period can be characterized by a convergence of (i) increasingly mechanism-centered therapeutic development and (ii) more explicit operationalization of clinical targets and monitoring across rheumatic and musculoskeletal diseases (RMDs).[1] EULAR 2025 messaging explicitly emphasized the portability of therapies across conditions because immune pathways are shared, and that innovative agents increasingly target “core immunologic mechanisms” rather than disease-specific phenotypes.[1] In practice, this conceptual shift coincided with concrete clinical innovations: CAR-T programs were presented as potentially “resetting” autoimmunity with meaningful clinical responses without ongoing immunosuppression, while targeted biologics and refined small molecules continued to mature via long-term extensions, real-world registries, and guideline updates.[4, 14, 15]
A second hallmark of this interval was maturation of implementation science in rheumatology: registries were positioned as drivers of quality and outcomes improvement, structured home monitoring models were evaluated for efficiency and cost-effectiveness, and AI-based tools were introduced for both imaging interpretation and patient-facing digital therapeutics—paired with explicit cautions that clinical expertise and human interaction remain essential.[13, 16, 17] Finally, interdisciplinary care and early screening gained momentum, exemplified by European CTD-ILD recommendations that strongly advocate systematic HRCT screening in SSc and MCTD regardless of risk factors and emphasize earlier treatment pathway entry.[18]
Rheumatoid arthritis
Novel therapies
In RA, 2025–2026 progress was less about single “new” blockbuster mechanisms and more about refining long-term efficacy, safety-informed sequencing, and access. Long-term extension data supported sustained efficacy of upadacitinib monotherapy, with continued effectiveness over five years and superior long-term efficacy versus methotrexate (MTX).[4] Alongside mature JAK inhibitor programs, early pipeline innovation was represented by a dual JAK/ROCK inhibitor (CPL’116) showing dose-dependent improvement in disease activity and joint counts in MTX-inadequate responders.[2]
Regulatory milestones also influenced the therapeutic landscape through biosimilar expansion. In February 2026, the CHMP adopted a positive opinion recommending marketing authorization for Tuyory (tocilizumab) for multiple indications including RA.[19] Similarly, Fubelv—positioned for use alone or with MTX—was described as reducing radiographic progression and improving physical function, signaling continued emphasis on broad access to effective biologic backbones via biosimilars and related products.[20]
Pivotal trials
The most quantitatively informative RA dataset in the provided 2025–2026 materials was the SELECT-EARLY upadacitinib monotherapy long-term extension versus MTX. At week 260, CDAI remission was achieved in 53%/59% of patients receiving upadacitinib 15/30 mg, compared with 43% receiving MTX (as-treated/observed analyses).[4] Boolean remission at week 260 was 23%/25% with upadacitinib 15/30 mg versus 12% with MTX (non-responder imputation).[4] Safety signals aligned with known JAK inhibitor risks: herpes zoster rates were higher with upadacitinib (3.9 and 4.5 events/100 patient-years for 15 and 30 mg) than with MTX (0.8 events/100 patient-years), with the highest rate in the 30 mg group.[4]
Real-world evidence complemented trial extensions by contextualizing persistence and discontinuation drivers. In a registry dataset including 1,361 JAK inhibitor initiators, the overall 3-year retention rate was 46%.[21] Discontinuations (523 patients) were predominantly due to ineffectiveness (67.5%) or adverse events (25.8%).[21]
Prevention-oriented signals also appeared. In ACPA-negative individuals with subclinical disease features, 9% of MTX-treated participants progressed to RA over 5 years compared with 32% in placebo, supporting continued development of biomarker-stratified prevention strategies.[11]
Guideline updates
EULAR’s updated RA management recommendations emphasized streamlining and clearer operational guidance. The task force agreed on 5 overarching principles and reduced the recommendations to 9.[15] The recommendations reiterated shared decision-making based on disease activity, safety, and patient factors (including comorbidities and structural damage progression).[6] A sequencing algorithm was stated explicitly: initially MTX ideally with short-term glucocorticoids (GCs), escalation to a biologic DMARD after insufficient response at 3–6 months, and consideration of JAK inhibitors only after careful risk assessment including major adverse cardiovascular events, malignancies, and thrombo-embolic events.[5] The GC strategy itself was operationalized with a tapering principle: short-term GCs may be used when initiating or changing csDMARDs but “should be tapered and discontinued as rapidly as clinically feasible.”[5]
The most clinically consequential update in long-term care may be in de-escalation language. While prior formulations allowed dose reduction in sustained remission after GC discontinuation, the new wording added a preference for DMARD continuation (with dose reduction still possible).[6] This aligns with explicit patient-facing language that careful reduction can succeed for some individuals but “completely stopping treatment is generally not advised,” and with the caution that stopping often leads to flare even when remission is sustained.[5, 6]
Systemic lupus erythematosus and lupus nephritis
Novel therapies
SLE innovation in 2025–2026 clustered around (i) B-cell–directed immune reset strategies and (ii) more scalable, patient-friendly biologic delivery.
Cellular immunotherapy entered mainstream rheumatology discourse via CD19 CAR-T programs. EULAR communications stated that CAR T-cell and other B-cell–depleting therapies may “reset the immune system” across multiple RMDs, enabling meaningful clinical responses without ongoing immunosuppression, and characterized CD19 CAR T-cell therapy as a novel deep B-cell depletion option with promising results across diseases.[14] In SLE-specific reporting, complete B-cell depletion within 7 days was described after treatment, and disease activity improved rapidly (SLEDAI-2K mean approximately 14 at baseline to approximately 4 at 60 days).[14]
At the biologic and regulatory level, subcutaneous self-administration of anifrolumab expanded. The FDA approval for a SC autoinjector (“Saphnelo Pen”) was reported as based on Phase III TULIP-SC results showing statistically significant and clinically meaningful disease activity reduction versus placebo while on standard therapy.[10] Secondary and exploratory endpoints included 29.0% DORIS remission and 40.1% attaining low-level disease activity (LLDAS).[10]
In 2026, late-stage data and regulatory momentum supported expansion of direct B-cell targeting beyond earlier paradigms. A 2026 report described Phase III ALLEGORY results (presented at SLEuro 2026 and published in March 2026) showing 76.7% SRI-4 response at 52 weeks with obinutuzumab plus standard therapy versus 53.5% with placebo (adjusted difference 23.1%, 95% CI 12.5–33.6; p<0.001).[9] The same report described reduced flare risk (BILAG hazard ratio 0.58; p=0.002).[9] The manufacturer framed obinutuzumab as potentially the first anti-CD20 therapy to directly target B cells in SLE and potentially become a new standard of care.[9]
Pivotal trials
The evidence base included both late-stage biologic trials and program-level operational targets for organ-threatening disease.
For anifrolumab SC, the primary endpoint was specified as BICLA at week 52 in TULIP-SC.[22] The same development program communicated DORIS remission (29.0%) and LLDAS attainment (40.1%) in pre-specified secondary/exploratory analyses for Saphnelo.[10]
For B-cell depletion, ALLEGORY’s SRI-4 response difference and flare reduction were quantified and positioned as pivotal 2026 evidence for obinutuzumab in SLE.[9]
For CAR-T in SLE, efficacy and toxicity signals were described in clinical reporting: rapid and deep B-cell depletion and early marked disease activity improvement were emphasized, alongside adverse events including cytokine release syndrome (CRS) in 12 patients, pneumonia in one patient, and low IgG.[14] A rare but severe infection signal was also noted: one fatal pneumococcal meningitis case reported 11 months after treatment and after B-cell recovery.[14]
Guideline updates
EULAR’s 2025 recommendations for SLE with kidney involvement standardized LN management with operational targets. The task force agreed on 4 overarching principles and 13 recommendations, evaluated for feasibility and impact on care.[7] Kidney biopsy was described as indispensable for any SLE patient with evidence of kidney involvement.[8]
The 2025 LN update emphasized time-bound treatment goals: optimization (preservation or improvement) of kidney function within 3 months and gradual reduction of proteinuria to a UPCR target below 700 mg/g by 12 months (and as low as possible thereafter).[8] Combination therapy was recommended for active LN, particularly with poor prognostic factors, including mycophenolate or low-dose IV cyclophosphamide plus belimumab, mycophenolate plus a calcineurin inhibitor (voclosporin or tacrolimus), or mycophenolate plus obinutuzumab.[8] Repeat biopsy was recommended in clinical uncertainty—such as evaluating response or worsening, or if immunosuppressive withdrawal is contemplated in sustained remission.[8]
Complementary reporting of LN guidance reiterated early quadruple-therapy frameworks (GC + hydroxychloroquine + immunosuppressant + CNI or biologic) and stated that EULAR did not distinguish CNI/biologic choice by renal histology class.[11] Broader nephroprotective measures (e.g., low-salt diet, RAAS blockade, and SGLT2 inhibitors) were discussed in LN guidance summaries, with the Task Force deeming these drugs offerable to stable patients with persistent proteinuria or eGFR 20–60 ml/min/1.73m2 despite limited prospective SLE data, and recommending delayed initiation for at least 6–12 months until disease stabilizes with immunosuppression.[11, 23]
ACR-aligned 2025 guidance for SLE overall emphasized uniform hydroxychloroquine use, limiting GC duration, and early conventional and/or biologic immunosuppressive therapy to achieve and maintain remission or low disease activity while minimizing toxicities.[24]
Spondyloarthritis
Psoriatic arthritis
Novel therapies
PsA innovation in the provided materials centered on expanding targeted cytokine and kinase options while improving objective monitoring. Sonelokimab (an IL-17A/IL-17F-targeting nanobody) was reported to show multidomain efficacy in PsA, with a majority of patients achieving minimal disease activity and “high rates of ACR70 and PASI 100,” and was described as well tolerated with no major safety concerns.[2] Selective TYK2 inhibition (deucravacitinib) advanced with phase 3 signals, with ACR20 responses exceeding 54% at week 16 and described as maintaining a clean safety profile.[1]
Imaging-informed positioning of biologics emerged from whole-body MRI work: adalimumab led to significant reductions in MRI-WIPE scores (median decrease 39) and joint synovitis scores (median decrease 23), while guselkumab and ustekinumab did not show significant imaging changes (despite clinical score improvements across all groups).[11]
Real-world combination strategies also appeared as exploratory signals. In one cohort, bDMARD plus JAK inhibitor combinations (most frequently IL-17 inhibitor plus JAK inhibitor) were reported with only one case of mild infectious stomatitis over 10.5 patient-years and no treatment discontinuation due to that event.[25]
Pivotal trials
The SPEED randomized trial (n=192) evaluated strategy-level decisions in early PsA with poor prognosis: standard step-up csDMARDs versus combination csDMARDs versus early TNF inhibitor induction.[11, 13] At 24 weeks, both early TNFi and combination csDMARD strategies provided better disease control than standard care, but by 48 weeks only early TNFi sustained significant benefit over step-up care.[13] Quantitatively, the mean PASDAS was lower with early TNFi (3.7) and combination csDMARDs (4.1) versus step-up csDMARDs (4.8), and early TNFi was superior to step-up by −1.09 on PASDAS with benefit sustained at 48 weeks.[11]
The TIGERS randomized controlled trial (n=32) provided a complementary “pivotal” lens via objective inflammation readouts: WB-MRI synovitis correlated strongly with SJC66 changes (rho 0.78; p=0.023), supporting WB-MRI’s ability to capture inflammation not fully reflected in clinical scores.[11]
Guideline updates
Within the supplied sources, guidance was primarily reiterated as treat-to-target. Treatment was described as targeting remission (or alternatively low disease activity) via regular assessment and therapy adjustment, and the findings on early biologic induction were presented as supportive of an EULAR-endorsed early-intervention treat-to-target approach in poor-prognosis PsA.[26]
Axial spondyloarthritis
Novel therapies
In axSpA, “novelty” in 2025–2026 was strongly represented by AI-enabled tools rather than a single new immunomodulator in the provided sources. An AI approach for imaging interpretation was described as using advanced algorithms to assess inflammatory and structural MRI changes, performing with high sensitivity/specificity, and flagging patients meeting clinical criteria despite falling outside standard imaging definitions—framed as bridging diagnostic gaps.[17]
A second innovation was a tested AI-powered digital therapeutic (Axia). In a 12-week randomized 1:1 study comparing Axia with treatment as usual, Axia improved disease activity and multiple patient-centered outcomes with statistically significant differences.[11]
Pivotal trials
The Axia 12-week randomized trial (n=200) reported mean disease activity improvement of −1.66 (SD 1.41) with Axia versus −0.11 (SD 1.15) with control (p<0.001).[11] Functional status improved with a −1.12 (SD 1.40) change in BASFI versus a +0.06 (SD 1.31) change in controls (p<0.001).[11] Quality of life improved by −2.51 (SD 2.55) versus −0.16 (SD 2.26) (p<0.001).[11] Response rates were higher with Axia (ASAS20 51% vs 9%; ASAS40 23% vs 3%; both p<0.001).[11]
Guideline updates
No axSpA-specific guideline update was provided in the source set. However, a large-exposure safety synthesis relevant to routine management reported that across >20,000 patient-years, secukinumab did not associate with increased major adverse cardiovascular events in psoriasis, PsA, or axSpA populations.[27]
Systemic sclerosis
Novel therapies
SSc advances in the provided materials were most concrete in SSc-associated interstitial lung disease (SSc-ILD), vascular complications (digital ulcers), and early cellular immune-reset programs.
For SSc-ILD, both guideline and trial-like signals supported IL-6 pathway targeting and JAK inhibition. A European guideline summary stated that patients with SSc-ILD with early diffuse SSc and signs of inflammation should be treated with tocilizumab, described as a strong recommendation.[18]
A parallel therapeutic direction was JAK inhibition: an SSc highlights report described reduced fibroblast migration from BAL with upadacitinib.[28] Cellular therapies were framed as immune reset with B-cell repertoire renewal and minimal CRS in early RESET SLE and REST SSc data.[3] A specific product (rese-cel) was described as showing evidence of efficacy off all immunomodulatory medications and steroids, with sustained benefit out to 6 months in one patient.[28] The broader CAR-T technology pipeline for progressive refractory SSc was described as including off-the-shelf allogeneic CAR-T cells, bispecific CAR-T cells, and CAR NK cells.[29] At the same time, a review emphasized practical limitations of autologous CAR-T (specialized setting, cost, and risks including CRS, neurotoxicity, and infection).[29]
Vascular complications also saw actionable signals: selexipag showed better healing outcomes, lower relapse, and reduced frequency of new digital ulcers compared with iloprost during follow-up at 6, 12, and 24 months (p=0.001), suggesting potential as a more effective long-term DU therapy in SSc.[28] The median selexipag dose was 1600 mg/day, and only 2 patients discontinued due to intolerance at 12 months.[28]
Pivotal trials
The most quantitative SSc-ILD evidence in the provided dataset concerned functional decline endpoints. An SSc highlights report indicated fewer patients in the upadacitinib group had clinically meaningful FVC decline (>5% or >10%) compared with mycophenolate mofetil (MMF).[28]
Comparative effectiveness evidence from EUSTAR cohort analyses suggested limits of upfront combination immunosuppression: ILD progression rates at 12 months were similar for MMF (29.2%), rituximab (28.1%), and combination therapy (27.4%), with no clear benefit of combination therapy over single agents at 12 months.[28]
For progressive pulmonary fibrosis criteria, a conference recap highlighted the need to balance early detection of progression with identifying higher long-term mortality when applying criteria in routine practice.[30]
Guideline updates
Guideline change in 2025 was especially salient for CTD-ILD. EULAR’s recommendations listing includes ERS/EULAR clinical practice guidelines for connective tissue disease–associated ILD published online first in September 2025.[31] In practical summary reporting, these guidelines strongly recommended systematic screening for ILD with HRCT in all SSc and MCTD patients regardless of risk factors, and this standardization was explicitly framed as enabling earlier entry into treatment pathways.[18]
Clinical implications
The most immediate clinical implication is earlier and more standardized SSc-ILD detection and pathway entry through systematic HRCT screening in SSc and MCTD.[18] For treatment selection, the evidence base supports tocilizumab for early diffuse inflammatory SSc-ILD (strongly recommended) and suggests JAK inhibition as a plausible alternative strategy needing further validation but supported by mechanistic and FVC-decline signals.[18, 28] For vascular disease, oral prostacyclin-pathway therapy (selexipag) may reduce relapse and new ulcer formation with relatively low discontinuation due to intolerance.[28] Finally, CAR-T–based immune reset is increasingly plausible but still constrained by the need for specialized settings and by uncertainties in long-term efficacy and safety; this caution was explicitly voiced as “long-term efficacy and safety remains to be established.”[3, 29]
Idiopathic inflammatory myopathies
Novel therapies
In IIM, FcRn inhibition and cellular therapies were the clearest 2025–2026 therapeutic themes in the provided sources. A clinical report described a trial evaluating subcutaneous efgartigimod (PH20) in adults with active idiopathic inflammatory myopathy.[32] The same reporting stated that the drug led to significant improvements in Total Improvement Score versus placebo and showed good tolerability and safety.[32] A conference highlight further described improved muscle strength and function with rapid onset of action in myositis.[2]
Cellular therapy was framed as a “remission-oriented future,” including claims that rese-cabtagene autoleucel induced drug-free remission in lupus and myositis.[1] In early clinical reporting on CAR-T for severe autoimmune diseases, a myositis-focused CAR-T approach was described as well-tolerated with no dose-limiting toxicity, CRS, or ICANS.[33]
Pivotal trials
For efgartigimod in IIM, the available evidence was phase-2-like: improved Total Improvement Score versus placebo and favorable safety/tolerability were stated, alongside an explicit rationale to continue evaluation in an ongoing phase 3 trial.[32]
For CAR-T, a phase 1/2 basket trial report stated that no CRS higher than grade 2 and no ICANS occurred, and that 22 of 24 patients achieved predefined efficacy endpoints; within IIM specifically, 4 of 5 reached ACR major/moderate response.[34] The same basket-trial source concluded that CASTLE suggests feasibility, safety, and efficacy of zorpo-cel across autoimmune diseases and “paves the way” for a pivotal study.[34]
Guideline updates
Although the source set did not include an IIM-specific guideline document, CTD-ILD guideline implementation language had direct relevance to myositis-associated ILD management; the guideline was framed as helping “get patients earlier into treatment,” and inclusion in EULAR guidance was framed as increasing likelihood of adoption in clinical practice to improve prognosis.[18]
Sjögren’s syndrome
The provided dataset contained only a single general statement supporting continued development in phase 3 trials, without Sjögren’s-specific quantitative endpoints or named trial documents in the available quotes.[2]
Vasculitis
ANCA-associated vasculitis
Novel therapies
In AAV, the clearest 2025–2026 signal in the provided materials was care-pathway optimization for ILD manifestations. A conference recap stated that prompt evaluation and early treatment by rheumatologists and pulmonologists was associated with good clinical outcomes regarding ILD progression and steroid-sparing effects.[30]
For refractory disease, CAR-T therapy was described through a case study of a 52-year-old man with severe AAV. After infusion, CAR-T cells expanded rapidly, peaking on day 14 and declining over six weeks.[33] The patient developed grade 1 CRS managed with tocilizumab and grade 3 neutropenia that resolved with filgrastim.[33] Symptoms resolved and granulomas stabilized, with the patient remaining symptom-free without immunosuppressive treatment despite return of CD19+ B cells at seven months.[33]
Guideline updates
No AAV-specific guideline updates were present in the provided quote set, and thus no guideline claims can be synthesized here without extending beyond the supplied evidence base.
Giant cell arteritis
Novel therapies
In GCA, novel directions in the provided materials spanned pathway innovation, AI-enabled diagnostics, and regulatory access expansion.
Mechanistically, complement inhibition was framed as promising in large vessel vasculitis (GCA) beyond the “recent success of JAK inhibitors.”[3] Separately, manufacturing innovation was highlighted for an off-the-shelf CAR-T platform derived from an iPSC-engineered clonal master cell bank, enabling mass production; early data from the first three patients in a multi-center phase 1 study were described as having a favorable safety profile, effective B-cell depletion with reconstitution of more naïve B cells, and promising initial efficacy.[33]
Regulatory access expanded via IL-6R blockade products: in February 2026, CHMP adopted a positive opinion recommending marketing authorization for Tuyory (tocilizumab) including for giant cell arteritis, and the EPAR specified that Tuyory is indicated for treatment of GCA in adult patients.[19] The EPAR also specifies that the active substance is tocilizumab, a recombinant humanized anti-IL-6 receptor monoclonal antibody.[19]
Clinical implications
The provided sources underscored cardiovascular and cerebrovascular risk in GCA: a conference recap reported increased risk of death and cardiovascular events, and increased cerebrovascular events, in patients with giant cell arteritis (with or without polymyalgia rheumatica).[30]
On the diagnostic side, a supervised deep learning model trained on 3,800 images from 244 patients was reported to excel at identifying abnormalities in key arteries in GCA ultrasound, with future work focusing on increasing dataset diversity and multi-center validation.[17]
Gout
Novel therapies
Urate-lowering pharmacotherapy innovation in 2025 focused on URAT1 inhibition and on strengthening the treat-to-target “implementation layer.” In a randomized double-blind phase 3 study, ruzinurad achieved target serum urate (sUA) ≤360 μmol/L in 52.6% at week 16 compared with 34.5% on allopurinol, and efficacy was sustained through week 52.[12] Serious treatment-emergent adverse events were described as relatively low (4.9% vs 3.1%) without new safety concerns.[12]
For long-term tolerability, a phase 2 open-label report for pozdeutinurad (AR882) described most treatment-emergent adverse events as mild-to-moderate and noted reduced flare frequency after the first six months; four serious adverse events occurred, none linked to study drugs.[12]
Pivotal trials
The ruzinurad phase 3 head-to-head trial (n=773) was explicitly described as randomized and double-blind and as demonstrating superior urate-lowering efficacy.[12] The target attainment difference at week 16 (52.6% vs 34.5%) and sustained efficacy through week 52 were the most directly actionable efficacy data provided.[12]
Beyond drug trials, observational evidence linked treat-to-target timing to cardiovascular outcomes. In linked primary care and hospital/mortality records from more than 116,000 patients, reaching sUA target within one year was associated with higher MACE-free survival and reduced cardiovascular risk.[12] Complementary reporting quantified a 5-year relative risk reduction range of 6%–11% and an absolute survival benefit of 1.3%–1.4%.[32]
Care models
Service delivery models were a distinct 2025 theme in gout. In an analysis of 442 patients, nurse-supported home monitoring produced a slight improvement in outcomes (QALY 1.45 usual care vs 1.46 home monitoring) and was described as an efficient approach that eases physician demand while maintaining outcomes.[13] Workload redistribution was quantified: rheumatologists saved 42.74 minutes over two years while nurses spent 51.21 more minutes per patient, consistent with task-shifting rather than net time elimination.[13] Economic modeling reported incremental net monetary benefit of 130.20 EUR and a 96% probability of cost-effectiveness at a 20,000 EUR/QALY threshold.[13]
Clinical implications
Collectively, the 2025–2026 evidence supports treating sUA targets not only as endpoints but as time-bound implementation goals, since earlier target attainment was associated with fewer cardiovascular events and higher MACE-free survival and was also linked to fewer gout flares.[12] It also supports pragmatic monitoring redesign, where nurse-led home monitoring can maintain outcomes, shift specialist time, and remain cost-effective in modeling analyses.[13] A risk-expansion implication was also highlighted: real-world gout data identified opportunities for proactive screening and prevention of fragility fractures, framed as an underrecognized issue in gout populations.[16]
Osteoarthritis
In osteoarthritis, a single 2025 abstract-level signal suggested that GLP-1 receptor agonists delivered greater improvements in pain and physical function than SGLT2 inhibitors, positioning metabolic therapies as potential symptom-modifying adjuncts in OA populations with relevant comorbidity profiles.[35]
Other areas
Palindromic rheumatism
A notable 2025 strategy trial signal in palindromic rheumatism (PALABA) framed PR as a modifiable pre-RA state. The primary outcome was development of RA at 2 years, which occurred in 28% with hydroxychloroquine versus 9% with abatacept.[11] Abatacept was also associated with fewer PR attacks (23% vs 56%).[11] RA-free survival over 24 months favored abatacept (log-rank p=0.029), and timing of RA progression differed (most HCQ progressions in the first 12 months versus RA progression after 18 months with abatacept).[11]
Immune checkpoint inhibitor-associated inflammatory arthritis
Mechanistic work using single-cell and spatial transcriptomics compared synovial tissue in spontaneous inflammatory arthritis versus checkpoint inhibitor-associated inflammatory arthritis and identified overlapping disease pathways.[32] The CIAIA synovium was described as enriched with fibroblasts and T cells, highly vascularized, and containing many CXCL9/10/11+ macrophages and CD8+ T cells.[32] These findings were explicitly framed as supporting the current use of TNF inhibitors for CIAIA while highlighting the need for further investigation regarding applicability to spontaneous arthritis.[32]
Cytokine release syndrome
Because cellular therapies expanded in rheumatology discussions in 2025–2026, supportive care for CAR-T toxicities became more relevant to rheumatology-adjacent practice. The FDA label for AVTOZMA (tocilizumab-anoh) states it is indicated for treatment of CAR T-cell–induced severe or life-threatening CRS in adults and pediatric patients ≥2 years old.[36] The EMA EPAR for Tuyory likewise specifies an indication for CAR T cell-induced severe or life-threatening CRS and describes the agent as an IL-6 receptor–blocking monoclonal antibody (tocilizumab).[19]
Cross-cutting themes
Cellular immune reset
Across diseases, the unifying “breakthrough” narrative was deep B-cell depletion and immune reset. EULAR communications suggested CAR T-cell therapy and other B-cell–depleting strategies may reset the immune system across multiple RMDs, enabling clinical responses without immunosuppressive therapies, and characterized CD19 CAR-T as a novel deep depletion option with promising results across diseases.[14] Programmatic reporting described the RESET program as inducing drug-free remission in SLE, myositis, and SSc.[2] Basket-trial evidence further quantified feasibility and safety: no CRS higher than grade 2 and no ICANS occurred, and 22/24 patients achieved predefined efficacy endpoints across SLE, SSc, and IIM cohorts.[34] At the same time, real-world clinical implementation must internalize infection and immunoglobulin risks, as CRS, pneumonia, and low IgG were reported in SLE CAR-T reporting and one fatal pneumococcal meningitis case was documented months after treatment.[14]
Small molecules and safety-informed sequencing
The RA dataset illustrated how long-term efficacy must be balanced with adverse events of special interest. SELECT-EARLY showed sustained remission/response endpoints with upadacitinib over five years but also higher herpes zoster rates versus MTX, especially at 30 mg.[4] EULAR sequencing language explicitly positioned JAK inhibitor use behind careful evaluation of specific risks (MACEs, malignancies, thrombo-embolic events), embedding pharmacovigilance concerns directly into treatment algorithms.[5]
Treat-to-target and de-escalation
Treat-to-target logic remained central but became more explicit about “what to do next” and “what not to stop.” In RA, EULAR reduced and clarified recommendations, formalized the MTX plus short-term GC start, and articulated escalation timing.[5, 15] For patients in sustained remission, the recommendations added a preference for DMARD continuation rather than stopping completely and underscored that stopping often leads to flare, shaping the emerging concept of “maintenance dosing” over withdrawal.[5, 6] In PsA, treat-to-target remission/low disease activity was reiterated and linked to early intensive induction strategies in poor-prognosis patients.[26]
Objective monitoring and AI
Across RMDs, objective monitoring broadened beyond standard clinical scores and clinician impressions. In PsA, WB-MRI synovitis correlated strongly with swollen joint count changes, supporting imaging’s ability to detect inflammation not fully reflected clinically.[11] In SSc-ILD, AI-based quantification was described as more precise for detecting progression and aligning with pulmonary function trends, potentially enabling earlier intervention.[17] In vasculitis, deep-learning ultrasound tools in GCA were reported to excel at identifying abnormalities in key arteries and were positioned for broader validation across centers.[17] Importantly, AI adoption was paired with explicit cautions that lower concordance in recommendations reinforces the need for clinical expertise and that AI should complement rather than replace healthcare professionals.[17]
Comorbidity screening and interdisciplinary care
CTD-ILD guidelines exemplified the move toward earlier standardized screening, with systematic HRCT screening recommended in all patients with SSc and MCTD regardless of risk factors; this was framed as enabling earlier treatment.[18] Complementary guidance commentary highlighted that “big news” includes screening RA patients with risk factors for ILD, expanding the ILD lens beyond classic CTDs.[18] In AAV-ILD, multidisciplinary rheumatology–pulmonology evaluation and early treatment were associated with good outcomes and steroid-sparing effects, reinforcing team-based care models.[30]
Discussion
The 2025–2026 evidence set points to a bifurcating innovation pathway: high-intensity cellular immune reprogramming is advancing in parallel with incremental but highly impactful optimization of chronic disease management through guidelines, safety data, monitoring, and service redesign. Mechanism-centric convergence suggests that a therapy developed for one condition may plausibly traverse to others when pathways align, a direction explicitly emphasized in EULAR 2025 messaging.[1]
At the same time, the data caution against premature celebration. Cellular programs carry non-trivial toxicity and infection considerations—CRS and hypogammaglobulinemia signals were reported, and severe infection can occur even after apparent immune recovery.[14] For chronic targeted small molecules, long-term extension and real-world persistence data emphasize the practical determinants of success: sustained efficacy, dose- and risk-informed monitoring, and adherence/persistence shaped by both ineffectiveness and adverse events.[4, 21]
Health-system innovation is increasingly a “breakthrough domain” in its own right. Nurse-led monitoring models and registry-enabled benchmarking illustrate pathways to maintain outcomes while reallocating specialist resources.[13, 16] Finally, equity factors remain a non-biologic determinant of outcomes: lower income or limited education were associated with 30–40% higher risk of early organ damage in SLE, highlighting the need for targeted interventions around access, literacy, and support.[13]
Conclusion
Across 2025–2026, rheumatology advances were defined by a combination of remission-oriented cellular immunotherapy signals, maturation of targeted small molecule/biologic strategies with long-term and real-world validation, and increasingly operational guideline frameworks that specify sequencing, safety, and monitoring. Mechanism-centric convergence and cross-disease portability were explicitly emphasized in EULAR 2025 narratives, while CAR-T programs provided early quantitative signals of feasibility and multi-disease activity—tempered by infection and toxicity considerations that demand specialized care pathways.[1, 14, 34] In parallel, guideline updates in RA and LN made treat-to-target more actionable, including explicit time-bound renal targets and a shift toward dose reduction rather than complete DMARD cessation in sustained remission.[6, 8] The net result is a field moving simultaneously toward curative-intent immunologic reset and toward higher-quality chronic care delivery grounded in evidence, safety, and implementation science.[13–15]
