OBJECTIVES: Immune checkpoint inhibitors (ICIs) are increasingly used in oncology, but concerns persist regarding flare risks of pre-existing rheumatologic diseases in patients receiving ICIs. This meta-analysis study ai...OBJECTIVES: Immune checkpoint inhibitors (ICIs) are increasingly used in oncology, but concerns persist regarding flare risks of pre-existing rheumatologic diseases in patients receiving ICIs. This meta-analysis study aims to evaluate the incidence and severity of rheumatologic disease flares in patients with solid tumors treated with ICIs. METHODS: We searched PubMed and Embase through May 2024 to identify studies reporting the incidences of pre-existing rheumatologic disease flare due to ICIs for their cancer. A random-effects proportional meta-analysis was conducted to pool the incidence of grade 1-5 and grade 3-5 flares, stratified by rheumatologic disease types and ICI subtypes. RESULTS: In total, 31 studies comprising more than 700 patients were identified for meta-analyses. The pooled incidence of grade 1-5 flare was 33.8% (95% confidence interval [CI]: 25.8-42.2%), with a median onset of 38.5 days (IQR: 30.0-52.6) after ICI initiation. Grade 3-5 flare incidence rate was 4.2% (95% CI: 0.6-9.6). Flare incidences varied among rheumatologic diseases: 40.9% in rheumatoid arthritis, 46.4% in psoriatic arthritis, 11.3% in systemic sclerosis, and 3.8% in systemic lupus erythematosus, respectively. For disease flares, 83% (n = 134/161) received systemic corticosteroids, and 81% (n = 30/37) of such cases had clinical improvement. ICIs were permanently discontinued in 17% of flare cases. CONCLUSIONS: Incidences of rheumatologic disease flare from ICIs vary depending on the underlying rheumatologic condition. This underscores the need for close communication between rheumatologists and oncologists to assess risk of flares prior to ICI initiation and manage both rheumatologic disease and cancer after the incidences of disease flares.
OBJECTIVE: To classify Still's disease (known as "systemic JIA") course into monophasic, polyphasic and chronic-persistent disease, using data collected before and after the introduction of biologic IL-1/6 inhibitors, an...OBJECTIVE: To classify Still's disease (known as "systemic JIA") course into monophasic, polyphasic and chronic-persistent disease, using data collected before and after the introduction of biologic IL-1/6 inhibitors, and identify predictors for a non-monophasic disease. METHODS: A multi-center, retrospective chart review from 3 hospitals in Israel and 2 in the US, involving patients diagnosed with Still's disease between 1998-2021, with a minimum follow-up of 1 year. RESULTS: Eighty-two patients met the inclusion criteria, with a median follow up time of 2.8 years (1.1-17). Fifty-two (63.4%) were females; mean age at diagnosis was 6.4 ± 4.4 years. Fifty-nine (72%) were diagnosed in 2012 or later, when IL-1 and IL-6 inhibitors became widely used. The rates of monophasic, polyphasic and persistent disease were 34.1%, 46.3% and 19.5%, respectively, with a higher-than-expected rate of polyphasic disease. The proportion of a non-monophasic (polyphasic or persistent) disease decreased from 78.2% in cases diagnosed before 2012 to 61% in cases diagnosed after 2012 albeit not statistically significant (p = 0.22). In a multivariate logistic regression model, an active disease 3 months from diagnosis was an independent risk factor for a non-monophasic disease course (OR 4.16 [1.33-15.2], p = 0.02). CONCLUSIONS: Drug-free remissions in chronic, non-monophasic Still's disease may be more common than previously demonstrated. In the age of IL-1 and IL-6 inhibitors, a monophasic disease course may be more prevalent. This finding provides further evidence that cytokine blockers may potentially alter the natural history of this disease, and that early aggressive treatment may be warranted.
Gavioli F, Caggiano V, Sbalchiero J
… +60 more, Frassi M, Crisafulli F, Cavazzana I, Hinojosa-Azaola A, Martín-Nares E, Guaracha-Basañez GA, Torres-Ruiz J, Wiesik-Szewczyk E, Sfriso P, Rizzo S, Schermi M, Bindoli S, Hernández-Rodríguez J, Gómez-Caverzaschi V, Araújo O, Alemanno A, Giardini HAM, González-García A, Placido F, Lopalco G, Viapiana O, Tufan A, Koksoy B, Mulayim F, Hissaria P, Beecher M, Panayiaris T, De Paulis A, Dagna L, Tomelleri A, Campochiaro C, Bugatti S, Milanesi A, Ruiz-Irastorza G, Soto-Peleteiro A, Piga M, Cauli A, Floris A, Conti F, Cardamone C, Zorzenon I, Triggianese P, Gurnari C, Vitetta R, Prete M, Racanelli V, Silvan F, Talarico R, Mayo-Juanatey A, Alegre-Sancho JJ, Renieri A, Bocchia M, Sicuranza A, Balistreri A, Sorrentino V, Frullanti E, Frediani B, Fabiani C, Cantarini L, Vitale A
BACKGROUND: VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome is an acquired autoinflammatory disorder characterized by severe chronic inflammation and an increased occurrence of hematologic neopl...BACKGROUND: VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome is an acquired autoinflammatory disorder characterized by severe chronic inflammation and an increased occurrence of hematologic neoplasms. Although chronic inflammation is a well-established risk factor for cancer, the specific contribution of UBA1 gene mutations to tumorigenesis remains unclear. Therefore, this study aimed to evaluate the overall cancer risk in patients with VEXAS syndrome, including both hematologic and non-hematologic neoplasms. METHODS: The relative risk (RR) of cancer was compared between VEXAS patients and a control cohort comprising individuals with Still's disease, Behçet's disease, and Schnitzler's syndrome. Logistic regression analysis was performed to identify variables potentially associated with cancer development. Patient's data were drawn from the International AutoInflammatory Disease Alliance (AIDA) Network registries for VEXAS syndrome, Still's disease, Behçet's disease, and Schnitzler's syndrome. RESULTS: Ninety-six VEXAS patients and 2181 controls were enrolled. To minimize selection bias, only subjects aged >60 years were included, yielding 90 and 174 individuals in the exposed and control groups, respectively. The overall RR for cancer in VEXAS patients was 1.93 (95 % Confidence Interval [C.I.] 1.03-3.60, p = 0.036). Logistic regression analysis identified associations between cancer development and relapsing polychondritis (RR = 2.67, 95 %C.I. 1.22-10.64, p = 0.01), the p.Met41Thr mutation (RR = 3.33, 95 %C.I. 1.29-17.33, p = 0.02), elevated serum erythrocyte sedimentation rate (RR = 1.02, 95 %C.I. 1.01-1.05 p = 0.01), and lactate dehydrogenase (RR = 1.02, 95 %C.I. 1.01-1.07 p = 0.04) levels outside of flares. CONCLUSIONS: VEXAS patients exhibit a significantly increased risk of both hematologic and non-hematologic malignancies compared with controls, particularly among those with RP, p.Met41Thr mutation, and persistent systemic inflammation.
OBJECTIVE: To assess the association between menopausal hormone therapy use and Rheumatoid Arthritis (RA) incidence among postmenopausal women. METHODS: A systematic review and meta-analysis were conducted following PRIS...OBJECTIVE: To assess the association between menopausal hormone therapy use and Rheumatoid Arthritis (RA) incidence among postmenopausal women. METHODS: A systematic review and meta-analysis were conducted following PRISMA guidelines. MEDLINE, Embase, and the Cochrane Library were searched up to October 2025 for observational studies evaluating menopausal hormone therapy use and RA risk. Pooled risk ratios (RR) with 95% confidence intervals (CIs) were calculated using random-effects models. Subgroup analyses explored current versus former use and therapy duration. RESULTS: Five studies comprising 22,291,843 person-years of follow-up were included. Overall, menopausal hormone therapy use was associated with a modestly increased RA risk (Rate Ratio 1.15, 95% CI 1.10-1.21, p < 0.001; I² = 0%). Current users had higher risk (Rate Ratio 1.18, 95% CI 1.00-1.37, p = 0.04) compared with former users (Rate Ratio 1.11, 95% CI 0.94-1.32, p = 0.20). Long-term use (≥4 years) conferred greater risk (Rate Ratio 1.19, 95% CI 1.07-1.33, p = 0.002). CONCLUSIONS: Current menopausal hormone therapy use is associated with a modestly higher incidence of rheumatoid arthritis. Although the absolute increase is small, the widespread use highlights the need for individualized risk-benefit assessment, especially in women with autoimmune susceptibility.
OBJECTIVES: Immunoglobulin (Ig)G4-related disease (IgG4-RD) can affect any organ, but coronary artery involvement (CAI) is a potentially life-threatening manifestation of this disease. In this scoping review, we critical...OBJECTIVES: Immunoglobulin (Ig)G4-related disease (IgG4-RD) can affect any organ, but coronary artery involvement (CAI) is a potentially life-threatening manifestation of this disease. In this scoping review, we critically appraised the literature on IgG4-related CAI, aiming to explore clinical, radiological and histopathological characteristics as well as treatment strategies and prognosis. METHODS: A comprehensive search was performed on January 02, 2025 in PubMed® to identify studies describing individuals with IgG4-related CAI, including both coronaritis (true arteritis of the coronary vessel wall) and periarteritis (peri-coronary involvement), and considering case reports, case series, retrospective cohort studies and observational studies. Two reviewers independently conducted the revision of literature under the guidance of the methodologist to identify eligible studies. Data extraction included clinical presentation, imaging findings, histopathology, treatment, and outcomes. Given the heterogeneity of the studies, descriptive statistical analysis was used whenever possible to summarise the data. RESULTS: Out of 964 screened references, 143 articles met the above-mentioned inclusion criteria. Most CAI cases were included in case reports (90.2 %), 7 % in case series and 2.8 % in retrospective cohort studies or observational studies. CAI predominantly affected males in the sixth decade of life and frequently coexisted with aortic and large vessel involvement. All segments of the coronary arterial tree could be involved, even the smallest branches. Images detected by various methods revealed several types of lesions: stenosis, wall-thickening, aneurysm, ectasia, pseudotumor, pseudoaneurysm, dissection, and soft tissue masses. Increase serum IgG4 levels and increased inflammatory markers were reported. Histopathology was consistent with IgG4-RD in all coronary samples obtained. Glucocorticoid therapy, alone or combined with immunosuppressants and/or surgical interventions, was the most commonly reported treatment. Rituximab seemed to be an effective therapy for IgG4-related CAI even without associated glucocorticoids. Despite treatment, relapse and progression of coronary lesions were noted in some cases. CONCLUSIONS: Early identification and multidisciplinary management og IgG4-related CAI are crucial to reduce morbidity and mortality. Available data on the response to various treatments are limited, as dedicated coronary artery imaging was not consistently obtained soon enough after treatment to assess response. In addition, long-term follow-up was not available for all patients. Further studies are required to understand the real prevalence, natural history, optimal diagnostic strategies, and therapeutic approaches for this serious condition.
INTRODUCTION: Transparent reporting of randomized controlled trials (RCTs) is essential to ensure research integrity. While registration practices of RCTs are improving, concerns remain regarding the adequacy of outcome...INTRODUCTION: Transparent reporting of randomized controlled trials (RCTs) is essential to ensure research integrity. While registration practices of RCTs are improving, concerns remain regarding the adequacy of outcome registration and the consistency of outcome reporting in publications. OBJECTIVES: To evaluate the adequacy of primary outcome registration and the consistency of outcome reporting between registry entries and publications in rheumatology RCTs. METHODS: We conducted a meta-research study including primary reports of RCTs in rheumatology published from 2009 to 2022. We assessed whether primary outcomes were adequately registered (presence of SPIRIT-based criteria: measurement, analysis metric, and time points). For adequately registered outcomes, we evaluated consistency between the registry and the published report. Logistic regression was used to explore factors associated with inadequate registration and inconsistent reporting. RESULTS: We analyzed 947 RCTs involving 1679 primary outcomes. Only 38% of trials adequately described all their primary outcomes in the registry. Of these adequately registered trials, 67% reported their primary outcomes consistently in the corresponding publication, meaning just 25% of trials met both criteria. The most common gap in outcome description was missing participant-level analysis metric, while the most prevalent inconsistency was related to changes in the timing of outcome assessment. Registration of adequately described primary outcome improved between 2009 and 2013 before plateauing, while consistency in reporting showed no improvement over time. CONCLUSION: Despite improvements in trial registration practices, major gaps persist in outcome specification and reporting consistency in rheumatology RCTs.
OBJECTIVES: The relationships between vaccines and the development of systemic lupus erythematosus (SLE) and related organ involvements remain unclear. METHODS: We analyzed data from the Vaccine Adverse Event Reporting S...OBJECTIVES: The relationships between vaccines and the development of systemic lupus erythematosus (SLE) and related organ involvements remain unclear. METHODS: We analyzed data from the Vaccine Adverse Event Reporting System (VAERS) during the period of 1990 to 2025 to determine the incidence of vaccine-associated SLE over time. The relationships between vaccines and the development of SLE and organ involvements were assessed by disproportionality and case-control analyses. RESULTS: 1976 (0.017%) cases of vaccine-associated lupus were identified amongst 11,301,263 adverse events (AEs) reported in VAERS (1990-2025). Median time from vaccination to symptom onset was 8 (0-8,070) days. The most common manifestations are musculoskeletal and connective tissue disorders (82.94%) followed by skin and subcutaneous tissue lesions (10.83%), while kidney and nervous system involvements are rare. 702 (40.48%) patients had serious outcomes, and 22 (3.13%) died. Human papilloma virus (HPV) vaccine is associated with lupus AEs, especially musculoskeletal/connective tissue disorders, kidney and nervous system involvements. Hepatitis B virus (HBV) vaccine also shows correlations with lupus AEs, particularly musculoskeletal/connective tissue disorders. COVID-19, influenza and zoster vaccines show no relationship with lupus AEs and specific organ involvements. Recombinant protein vaccines show significant links with lupus AEs. CONCLUSION: Vaccine-associated lupus is uncommon and manifestations are generally mild. HPV and HBV vaccines show strong associations with lupus AEs with distinct organ involvements.
OBJECTIVES: Sjögren disease (SjD) is a common systemic autoimmune disease and patients experience a wide range of symptoms with unique emotional, social and physical impacts. Understanding the individual experience of Sj...OBJECTIVES: Sjögren disease (SjD) is a common systemic autoimmune disease and patients experience a wide range of symptoms with unique emotional, social and physical impacts. Understanding the individual experience of SjD is crucial to providing comprehensive and sensitive care in the clinics. Therefore, the aim of this systematic review was to analyze primary literature that examined the lived experiences of patients with SjD. METHODS: Primary literature qualitatively exploring the lived experiences of SjD patients through interviews and/or focus groups were identified. Papers were included if they were written in English, participants were ≥ 18 years old and they fulfilled a diagnosis of SjD as per the 2002 American-European Consensus or 2016 American College of Rheumatology/European Alliance of Associations for Rheumatology criteria. Thematic analyses were performed using the Thomas and Harden approach. RESULTS: Nine of 1990 screened manuscripts (0.5 %) fulfilled our selection criteria. These comprised a total of 162 participants (154, 95 % female) across 10 countries. Thematic analysis revealed several key themes: the burden of the physical symptoms (such as sicca), social isolation, negative impact on function, unpredictability of the disease, diverse coping strategies, and the challenges of navigating the healthcare system. Few studies addressed any bias in the recruitment of patients or analyses of data. CONCLUSION: SjD patients encounter a large variety of individual experiences in their illness that have important repercussions on quality of life. Understanding these experiences will help create a harmonized set of patient-centered outcomes to inform the generation of Outcome Measurement in Rheumatology (OMERACT) target domains in SjD.
INTRODUCTION: International guidelines state that all immunocompromised adults should be vaccinated with the recombinant varicella zoster virus (VZV) vaccine. We aimed to assess the risk factors for herpes zoster (HZ) in...INTRODUCTION: International guidelines state that all immunocompromised adults should be vaccinated with the recombinant varicella zoster virus (VZV) vaccine. We aimed to assess the risk factors for herpes zoster (HZ) in patients with systemic lupus erythematosus (SLE). METHODS: Electronic medical records of all SLE patients registered at our referral centre were analysed at the time of clinical visit between July and December 2024. Demographic, medical history, laboratory and treatment data were extracted using a standardised data collection form. Herpes zoster incidence and associated factors were identified. RESULTS: A total of 224 SLE patients (female 93.8 %, median age 48 [38;56] years) were included. Of these, 30 (n = 30/224, 13.4 %) had HZ. The incidence was 0.81 for 100 patient-years. Univariable analysis showed that gamma globulin level (OR 0.81, 95 %CI 0.70-0.92), duration of steroid treatment (OR 1.07, 95 % CI 1.03-1.11), immunosuppressive (IS) drugs (OR 2.41, 95 % CI 1.06-6.05), duration of IS treatment (OR 1.05, 95 % CI 1.00-1.09) and biologics (OR 3.50, 95 % CI 1.53-7.93) were significantly associated with HZ. In a multivariable logistic regression analysis, only gamma globulin level (OR 0.86, 95 % CI 0.74-0.98) remained independently associated with HZ. The ROC curve for gamma globulin levels showed significant associations with HZ (AUC = 0.71 (0.59-0.82)), with a threshold of 10.3 g/L providing the best discrimination between SLE patients with and without HZ. CONCLUSION: A reduced level gammaglobulin - with a cut-off of 10.3 g/L - is associated with HZ in SLE and may identify SLE patients who should be prioritized for VZV vaccination.
Van der Heijden H, Alonzi G, Cao A
… +13 more, van Gool R, Yekedüz MK, Vrolix L, Ronen I, Rameh V, McBrearty K, Deokar A, Sundel RP, Muscal E, Gonzalez-Heydrich J, Knight A, Chang JC, Upadhyay J
Semin Arthritis Rheum
· 2026 Apr · PMID 41564829
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OBJECTIVE: Cognitive dysfunction (CD) is a prevalent symptom in childhood-onset systemic lupus erythematosus (cSLE). This study aimed to investigate the neurobehavioral basis of CD in cSLE. METHODS: Patients with cSLE (N...OBJECTIVE: Cognitive dysfunction (CD) is a prevalent symptom in childhood-onset systemic lupus erythematosus (cSLE). This study aimed to investigate the neurobehavioral basis of CD in cSLE. METHODS: Patients with cSLE (N=20) and age- and sex-matched healthy controls (HCs, N=20) completed questionnaires and multiple neurocognitive tests. The Systemic Lupus Erythematosus Disease Activity Index 2000 and laboratory markers were used to monitor patients' clinical status. Neuroimaging assessments included functional near-infrared spectroscopy (fNIRS), functional magnetic resonance imaging (fMRI), and structural MRI. RESULTS: cSLE patients demonstrated moderate disease activity with high inflammation and immune dysregulation, alongside low medication adherence. Relative to HCs, cSLE patients showed worse cognitive functioning, higher emotional distress and more physical symptoms. fNIRS revealed higher prefrontal cortex activity in cSLE vs. HCs during the color-word Stroop task, suggesting impaired cognitive flexibility. fMRI performed during the N-back working memory task revealed altered frontal cortex and cerebellum activity, while modulations in resting-state fronto-cerebellar connectivity in the cSLE cohort were observed. Patients with cSLE were characterized by reduced gray matter morphological properties in frontal cortex and cerebellar subdivisions (e.g., crus II) alongside altered white matter structural connectivity among these cognitive processing hubs. K-means clustering analysis delineated three subgroups within the cSLE cohort based on neuroimaging profiles, where subgroups varied based on cognitive and emotional health. CONCLUSION: This study provides evidence of fronto-cerebellar abnormalities and their associations with CD in cSLE. This investigation underscores the need for multidisciplinary research efforts to further elucidate the neurobiological underpinnings of CD in cSLE.
BACKGROUND: How depression and anxiety symptoms affect fibromyalgia (FM) phenotypes and initial treatment outcomes remains unclear. This study prospectively investigated the impact of psychological symptoms on disease ma...BACKGROUND: How depression and anxiety symptoms affect fibromyalgia (FM) phenotypes and initial treatment outcomes remains unclear. This study prospectively investigated the impact of psychological symptoms on disease manifestations and therapeutic responses in individuals with newly diagnosed FM. METHODS: FM patients and healthy controls were prospectively recruited and assessed with questionnaires measuring emotional symptoms and disease conditions. The effects of anxiety and depression symptoms on FM manifestations and therapeutic responses (using pregabalin with/without imipramine; no placebo control) were investigated using cluster, correlation, regression, and mediation analyses through a 4-week follow-up. RESULTS: One hundred twelve newly diagnosed FM cases were included. Based on their psychological symptoms, patients were classified into two subgroups exhibiting different phenotypes; patients with prominent anxiety and depression symptoms (FM-AD) had more intense pain, worse disease severity, and poorer therapeutic responses than those without (FM-nAD; all p < 0.001). Correlation analyses showed that, along with pain, both depression and anxiety symptoms crucially modulated disease severity (all p < 0.001). Although pain relief conduced clinical improvement overall, linear mixed-effect regression analysis denoted that depression remission (p = 0.039), but not pain reduction (p = 0.062), determined clinical improvement for FM-AD cases. Notably, depression remission exerted a direct impact (p = 0.003) on disease improvement in FM-AD cases, independent of pain reduction (indirect effect: p = 0.101). CONCLUSION: Psychological symptoms, as much as pain, vitally determined disease severity in FM. For FM-AD individuals, alleviation of depression, rather than pain relief alone, pivotally predicted disease improvement. Early detecting and addressing depression in FM management could help with discriminating phenotypes, thereby improving FM care strategy.
OBJECTIVE: To identify predictors of cardiovascular (CV) events in psoriatic arthritis (PsA) patients from the CARdiovascular in RheuMAtology (CARMA) project during 10 years of prospective follow-up. METHODS: Between Jul...OBJECTIVE: To identify predictors of cardiovascular (CV) events in psoriatic arthritis (PsA) patients from the CARdiovascular in RheuMAtology (CARMA) project during 10 years of prospective follow-up. METHODS: Between July 2010 and January 2012, 725 PsA patients were enrolled from 67 Spanish hospitals. Analyses focused on 682 patients without prior CV events at baseline. At 10-year follow-up, CV event occurrence, patient-years, and linearized event rates were evaluated. Cox regression analyses were performed, both crude and adjusted for the PREVENT-CVD score. RESULTS: Over 6397 patient-years, 85 patients (12.46%) experienced CV events, yielding a rate of 1.33 per 100 patient-years. Patients with CV events were older (67.1 ± 11.1 vs. 56.7 ± 11.8 years, p < 0.001), more often male (68.2% vs. 51.9%, p = 0.005), and had higher frequencies of hypertension (60.0% vs. 21.8%, p < 0.001), diabetes (18.8% vs. 6.0%, p = 0.001), and dyslipidemia (56.5% vs. 29.8%, p < 0.001). They also showed greater abdominal perimeter and body mass index (p < 0.05 for both). After adjusting for PREVENT-CVD, the highest tertile of DAS28-ESR remained a significant predictor of CV events (HR 1.79; 95%CI: 1.03-3.14; p = 0.04). Urate in the highest tertile was also independently associated in the crude model (HR 1.88; 95%CI: 1.11-3.20; p = 0.02). When stratified (<6.5, 6.5-8.9, and ≥9.0 mg/dl), urate≥9.0 mg/dl was also associated with increased risk of CV events in the adjusted model (HR 3.50; 95%CI: 1.10-11.2; p = 0.02). While HAQ score in the third tertile was associated with increased CV risk in the crude analysis (HR 1.70; p = 0.04), this association did not persist after adjustment. CONCLUSIONS: Disease activity and elevated urate levels independently predict CV events in PsA, highlighting their value as markers of CV risk beyond traditional factors captured by the PREVENT-CVD score.
OBJECTIVE: To predict which early RA-patients achieve clinical remission on initial treatment with methotrexate monotherapy or with abatacept+methotrexate. METHODS: This study is a subanalysis of the AVERT and AVERT-2 ra...OBJECTIVE: To predict which early RA-patients achieve clinical remission on initial treatment with methotrexate monotherapy or with abatacept+methotrexate. METHODS: This study is a subanalysis of the AVERT and AVERT-2 randomized controlled trials, which were performed in ACPA-positive early RA-patients who received methotrexate monotherapy or abatacept + methotrexate. External model validation of patients on methotrexate monotherapy was performed in the observational Leiden Early Arthritis Clinic (EAC) cohort. Primary outcome was DAS28-CRP remission at 6 and 12 months follow-up. Prediction models were developed using logistic regression analysis. First, a model including clinical baseline variables only was estimated. Subsequently, it was assessed whether adding serological or imaging data, shared epitope or early DAS28 response improved model performance. RESULTS: In the methotrexate-monotherapy group (n=388), 27% and 39% of patients achieved DAS28-remission after 6 and 12-months. In the abatacept + methotrexate group (n=743) this was 43% and 53%. Baseline DAS28-CRP was predictive for clinical remission in all models. Optimism-adjusted model performance (AUROC) for DAS28-remission at 6 and 12-months was 0.66/0.65 in the methotrexate-group and 0.68/0.59 in the abatacept + methotrexate group. Adding baseline MRI-detected joint-inflammation, baseline serology or HLA-shared epitope alleles did not significantly improve model performance. Early DAS28-response did improve model performance. In the external validation cohort model performance was very similar. CONCLUSION: Determining which patients achieve clinical remission upon methotrexate or abatacept+methotrexate treatment remains challenging. Disease activity at disease presentation and early DAS response were the only consistent predictors for achieving clinical remission. Genetic, imaging and serology parameters did not improve model performance.