Clinical Disease Activity Index Research Articles

Predictive factors and treatment outcomes associated with difficult-to-treat rheumatoid arthritis conditions: the ANSWER cohort study.

To investigate the predictive factors for difficult-to-treat rheumatoid arthritis (D2T RA) and assess the efficacy of biological disease-modifying antirheumatic drugs (bDMARDs) and Janus kinase inhibitors (JAKi). Retrospective analysis was conducted on data from the ANSWER cohort comprising 3,623 RA patients treated with bDMARDs or JAKi in Japan. Multivariate Cox proportional hazards modelling was used to analyse the hazard ratios (HRs) for treatment retention. Of these, 450 (12.4%) met the first two criteria of EULAR D2T RA definition (defined as D2T RA in this study). Factors contributing to D2T RA included age over 75 (compared to those under 65, HR = 0.46, 95% CI: 0.31 to 0.69), higher rheumatoid factor (RF) titres (HR = 1.005, 95% CI: 1.00 to 1.01), higher clinical disease activity index (HR = 1.02, 95% CI: 1.01 to 1.03), lower methotrexate dosage (HR = 0.97, 95% CI: 0.95 to 0.99), and comorbidities like hypertension (HR = 1.53, 95% CI: 1.2 to 1.95) and diabetes (HR = 1.37, 95% CI: 1.09 to 1.73). Anti-interleukin 6 receptor antibodies (aIL-6R, HR = 0.53, 95% CI: 0.37 to 0.75) and JAKi (HR = 0.64, 95% CI: 0.46 to 0.90) were associated with fewer discontinuations due to ineffectiveness compared to tumour necrosis factor inhibitors. Oral glucocorticoids usage (HR = 1.65, 95% CI: 1.11 to 2.47) was linked to increased discontinuation due to toxic adverse events. Younger onset, higher RF titres, and comorbidities predicted D2T RA development. For managing D2T RA, aIL-6R and JAKi exhibited superior drug retention.

Plasma mtDNA as a possible contributor to and biomarker of inflammation in rheumatoid arthritis

ObjectivesNeutrophil extracellular trap formation and cell-free DNA (cfDNA) contribute to the inflammation in rheumatoid arthritis (RA), but it is unknown if mitochondrial DNA (mtDNA) or nuclear DNA (nDNA) is more abundant in the circulation. It is unclear if DNA concentration measurements may assist in clinical decision-making.MethodsThis single-center prospective observational study collected plasma from consecutive RA patients and healthy blood donors. Platelets were removed, and mtDNA and nDNA copy numbers were quantified by polymerase chain reaction (PCR).ResultsOne hundred six RA patients and 85 healthy controls (HC) were recruited. Circulating median mtDNA copy numbers were increased 19.4-fold in the plasma of patients with RA (median 1.1 x108 copies/mL) compared to HC (median 5.4 x106 copies/mL, p<0.0001). Receiver operating characteristics (ROC) curve analysis of mtDNA copy numbers identified RA patients with high sensitivity (92.5%) and specificity (89.4%) with an area under the curve (AUC) of 0.97, p <0.0001 and a positive likelihood ratio of 8.7.Demographic, serological (rheumatoid factor (RF) positivity, anti-citrullinated protein antibodies (ACPA) positivity) and treatment factors were not associated with DNA concentrations. mtDNA plasma concentrations, however, correlated significantly with disease activity score-28- erythrocyte sedimentation rate (DAS28-ESR) and increased numerically with increasing DAS28-ESR and clinical disease activity index (CDAI) activity. MtDNA copy numbers also discriminated RA in remission (DAS28 <2.6) from HC (p<0.0001). Also, a correlation was observed between mtDNA and the ESR (p = 0.006, R= 0.29). Similar analyses showed no significance for nDNA.ConclusionIn contrast to nDNA, mtDNA is significantly elevated in the plasma of RA patients compared with HC. Regardless of RA activity, the abundance of circulating mtDNA is a sensitive discriminator between RA patients and HC. Further validation of the diagnostic value of mtDNA testing is required.

Eye involvement in patients with rheumatoid arthritis: a cross-sectional study

Background: Rheumatoid arthritis (RA) is a systemic immune disease. The authors aimed to report the characteristics of ocular manifestations in patients with RA. Methods: Demographic and clinical characteristics were collected including: age, sex, and BMI. Disease data included the duration, the present main complaint, including the number of painful and swollen joints, duration of morning stiffness, and the patient’s self-evaluation form had also been applied and registered. Eye symptom including pain, dryness, redness, photophobia, discharge, and blurred vision was asked and registered, in addition to full medical history, treatment, and evaluation of clinical disease activity index. Rheumatologic examination included: the number of tender and swollen joints in patients was done. All study subjects underwent complete ophthalmological examination in the following manner: visual acuity assessment by Snellen’s chart, evaluation of pupil diameter and reflexes as well as eyeball movements, tear film evaluation by using Schirmer’s test, intraocular pressure measurement, slit-lamp evaluation of the anterior segment with concentration on ocular surface assessment, followed by installation of topical mydriatic/cycloplegic eyedrops for posterior eye segment exam and fundoscopy. Laboratory tests included rheumatic factor, anti cytoplasmic citrulinted peptide, C-reactive protein, and erythrocyte sedimentation rate were performed and analyzed. Results: Mean age of study group was 41.5±10 years,78.59% of which were females. Ocular manifestations were present in 31.14%. Dry eye was diagnosed in (36.71%), among which burning sensation was found in (35.15%), and photophopia in (27.34%). The most frequent ocular manifestation was episcleritis (66.40%), while scleritis was diagnosed in (22.65%), and keratoconjuctivitis was present in (7.04%). Discussion: The most common manifestations of ocular involvement in our RA patients was episcleritis, dry eye, and scleritis. Positive serum rheumatoid factor and anticitrulinated peptide antibody significantly increased the risk of having ocular manifestations, especially dry eyes, and the ocular manifestations prevalence was higher among male patients, long disease duration and treatment with biologics and disease-modifying antirheumatic drugs. Conclusion: Ocular symptoms are relatively frequent manifestation of RA. Regular ophthalmological examinations are essential among patients with RA.

Level of glial cell derived neurotrophic factor in the blood plasma of rheumatoid arthritis patients and its relationship with alexithymia

ObjectivesGlial cell derived neurotrophic factor (GDNF) has an important role in the pathogenetic mechanisms and clinical manifestations of rheumatoid arthritis (RA). Alexithymia is associated with a severe clinical course and worse prognosis, while the relationship between alexithymia and GDNF in RA patients has not been investigated before. The aims of the study were to investigate the GDNF level in blood plasma in RA patients depending on the presence of alexithymia and to evaluate the relationship of GDNF level with clinical manifestation and quality of life.Material and methodsFifteen men and 73 women with RA were examined using the Disease Activity Score with 28-joint count (DAS28) with erythrocyte sedimentation rate (ESR) index, the Simple Disease Activity Index (SDAI), the Rheumatoid Arthritis Clinical Disease Activity Index (CDAI), the Visual Analogue Scale (according to the assessment of the patient – VAS-P and the assessment of the doctor – VAS-D), the Health Assessment Questionnaire (HAQ), the Toronto Alexithymia Scale (TAS-20), the Disability Rating Index (DRI) and SF-36 indexes. Glial cell derived neurotrophic factor level in the blood plasma was determined by enzyme-linked immunosorbent assay (ELISA).ResultsForty percent of RA patients had alexithymia. Glial cell derived neurotrophic factor level in the examined patients was 3.73 ±2.59 pg/ml, in patients with alexithymia 4.08 ±2.87 pg/ml, without alexithymia 3.48 ±2.37 pg/ml (p = 0.295). Patients with alexithymia had a higher erythrocyte sedimentation rate (ESR) and index scores than patients without alexithymia – ESR: 34.29 ±14.22 vs. 22.73 ±12.03 mm/h (p = 0.017), DAS28: 6.53 ±0.66 vs. 6.09 ±0.55 (p = 0.017), VAS-D: 7.19 ±0.81 vs. 6.53 ±0.83 (p = 0.020), HAQ: 1.78 ±0.58 vs. 1.51 ±0.54 (p = 0.040). Also they had worse SF-36 indicators – physical functioning: 39.52 ±13.78 vs. 51.00 ±14.90 (p = 0.019), role functioning due to physical condition: 30.95 ±20.77 vs. 46.67 ±24.76 (p = 0.041), physical component of health: 31.47 ±11.44 vs. 41.61 ±15.88 (p = 0.028). In patients with alexithymia, a correlation was found between the GDNF level and severity of pain according to VAS-P: rS = 0.338, p = 0.044, and VAS-D: rS = 0.446, p = 0.006.ConclusionsAlexithymia was found in 40% of RA patients. Rheumatoid arthritis patients with alexithymia had a nonsignificantly higher GDNF level compared to patients without alexithymia. In RA patients with alexithymia, an association of GDNF level in the blood plasma with RA activity, loss of functional capacity and reduced quality of life was established. Alexithymia in RA patients is an important factor in the clinical manifestation of RA and modification of the pathophysiological role of GDNF.

Real-world experience with filgotinib for rheumatoid arthritis in Germany : Aretrospective chart review.

Real-world data for filgotinib, aJanus kinase (JAK)1 inhibitor, are limited in patients with rheumatoid arthritis (RA). To explore real-world filgotinib use in patients with RA in Germany. This retrospective chart review included patients aged ≥ 18years with confirmed moderate to severe RA who initiated filgotinib before December1, 2021, with ≥ 6months of medical records available prior to filgotinib initiation or after initial diagnosis. Patient characteristics, prior treatments, reasons for initiating/discontinuing filgotinib, disease activity, dose adjustments and concomitant treatments were recorded. In total, 301 patients from 20 German rheumatology outpatient units were included. One-third were aged ≥ 65years and almost half had ≥ 1 cardiovascular (CV) risk factor. Most patients initiated filgotinib as monotherapy (83.7%; 12.7% of whom with glucocorticoids) and at the 200 mg dose (84.7%); higher proportions of those initiating the 100 versus 200 mg dose were aged ≥ 65years and had renal impairment or ≥ 1 CV risk factor. Oral administration (78.4%), fast onset of action (66.8%) and administration as monotherapy (65.4%) were the most common reasons for initiating filgotinib. At 12months, 41 (18.4%) patients had discontinued filgotinib, most commonly due to lack of effectiveness. After 6‑months of follow-up, 36.8% of patients had achieved Clinical Disease Activity Index (CDAI) remission and 45.6% had achieved CDAI low disease activity. In clinical practice in Germany, reasons for initiating filgotinib in patients with RA were related to dosing flexibility and general JAK inhibitor attributes. Filgotinib was used predominantly as monotherapy and was effective and generally well tolerated; however, longer-term data in larger, prospective cohorts are needed.

Physician estimate of inflammation vs global assessment in explaining variations in swollen joint counts in rheumatoid arthritis patients

Abstract Objective To analyze patients with rheumatoid arthritis (RA) for inflammatory activity by physician estimate of global assessment (DOCGL) vs an estimate of inflammatory activity (DOCINF) to explain variation in swollen joint count (SJC). Methods Patients with RA were studied at routine care visits. Patients completed a multidimensional health assessment questionnaire (MDHAQ), and the physician completed a 28-joint count for swollen (SJC), tender (TJC) and deformed (DJC) joints, and a RheuMetric checklist with a 0–10 DOCGL visual numeric scale (VNS), and 0–10 VNS estimates of inflammation (DOCINF), damage (DOCDAM) and patient distress (DOCSTR). Disease activity score 28 (DAS28-ESR), clinical disease activity index (CDAI) and routine assessment of patient index data (RAPID3) were calculated. Individual scores and RA indices were compared according to Spearman correlation coefficients and regression analyses. Results 104 unselected patients were included, with median age and disease duration of 55.0 and 5 years respectively. Median (IQR) DAS28-ESR was 2.89 (1.64), indicating low activity. DOCINF was correlated significantly with DOCGL (rho= 0.775). Both DOCGL and DOCINF were correlated significantly with most other measures; correlations with DOCGL generally were higher than with DOCINF other than for SJC. In regression analyses, DOCINF was more explanatory of variation in SJC than DOCGL and other DAS28-ESR components. Conclusions Variation in SJC is explained more by a 0–10 DOCINF VNS than the traditional DOCGL or any other measure in routine care RA patients. DOCINF on a RheuMetric checklist can provide informative quantitative scores concerning inflammatory activity in RA patients monitored over long periods.

Clinical disease activity index versus disease activity score (28 joints) for assessment of disease activity in obese patients of rheumatoid arthritis

Background: Measurement of disease activity by Disease Activity Score 28 joints -Erythrocyte Sedimentation Rate (DAS28-ESR), Disease Activity Score (28 joints)-C-Reactive Protein (DAS28-CRP), and Clinical Disease Activity Index (CDAI) has become an integral part of management of Rheumatoid Arthritis (RA), by ‘Treatment to Target’ approach. With the exception of CDAI, the other two use inflammatory markers ESR and CRP to measure disease activity. Obesity is also known to increase inflammatory markers like CRP. We undertake this study to examine if obesity confounds the disease activity measurement in RA leading to overestimation of disease activity. Methods: A cross-sectional observation study was conducted on one hundred patients of RA (40 obese and 60 non obese) in remission or low disease activity as defined by CDAI. They were divided into obese and non-obese groups based on Indian standards (BMI&gt;25kg/m2). ESR and CRP were measured in both the groups. DAS28-ESR and DAS28-CRP were calculated and compared using relevant statistical tests. Results: DAS28-ESR and DAS-28-CRP scores were significantly higher in the obese subjects, despite both groups having comparable CDAI scores. Similar findings were also observed with inflammatory markers ESR and CRP, both being higher in obese patients. Conclusions: We conclude that indices incorporating inflammatory markers, like DAS28 overestimate disease activity in obese RA patients. Treatment decisions regarding escalation or addition of DMARDs should be taken after considering the same. CDAI appears to be better suited for disease activity measurements in obese RA patients as compared to DAS 28.

P127 Comparison of the Efficacy, Safety and Immunogenicity of a Proposed Biosimilar MSB11456 with Tocilizumab Reference Product in Moderate-to-Severe Rheumatoid Arthritis: Results of a Randomized Double-Blind Study

Abstract Background/Aims Tocilizumab is an anti-interleukin-6 receptor monoclonal antibody indicated for treating rheumatoid arthritis (RA) and other inflammatory diseases. MSB11456 is a proposed biosimilar to US-licensed tocilizumab and EU-approved tocilizumab. It has already shown equivalent pharmacokinetic, pharmacodynamic safety, tolerability, and immunogenicity profiles to these products given subcutaneously (SC) as a single dose in healthy volunteers. This Phase III, multi-centre, randomised, double-blind, multiple fixed-dose, parallel group study compared efficacy, safety and immunogenicity of MSB11456 and EU-approved tocilizumab administered SC in moderate-to-severe RA patients. Methods Patients were randomised to 162mg MSB11456 or EU-approved tocilizumab for 24 weeks (W). At W24, patients receiving EU-approved tocilizumab were re-randomised to continue treatment or switch to MSB11456 for up to W52. Safety evaluations were conducted up to W63. A change from baseline in Disease Activity Score-28 Joint Count-ESR (DAS28-ESR) at W24 was analysed, as the primary efficacy endpoint, using analysis of covariance to determine the least squares mean (LSM) difference between MSB11456 and EU-approved tocilizumab; equivalence was considered if the 90% confidence interval (CI) was entirely within the FDA equivalence interval -0.6 to 0.5. Secondary endpoints were 20% improvement in ACR core set measures at W24 and DAS28-ESR at W12. Additional endpoints included ACR50/70, change in DAS28-CRP, Simplified and Clinical Disease Activity Indexes, evaluation of immunogenicity up to W55 and safety up to W63. Results Clinically relevant LSM decreases from baseline in DAS28-ESR were observed from W2 up to W24 with both treatments. The 90% CI for LSM difference in the change from baseline in DAS28-ESR between treatments was fully included within the predefined equivalence interval, which demonstrated therapeutic equivalence of MSB11456 and EU-approved tocilizumab (Table 1). Other efficacy endpoint analyses supported this conclusion. No discernible patterns in the nature or frequency of treatment-emergent adverse events (TEAEs) were identified to suggest a difference between drugs. Anti-drug antibodies incidence was similar among treatment arms. Switching from EU-approved tocilizumab to MSB11456 had no clinically relevant impact on efficacy or safety. Conclusion Equivalent efficacy, immunogenicity and safety profiles of MSB11456 and EU-approved tocilizumab were demonstrated in moderate-to-severe RA patients, confirming equivalence between MSB11456 and the EU-approved tocilizumab. Disclosure A. Zubrzycka-Sienkiewicz: None. M. Misterska-Skora: None. M. Socik-Pojawa: None. K. Klama: None. M. Ullman: Other; Employee of Fresenius Kabi SwissBioSim - Sponsor of the study. C. Petit-Frere: Other; Employee of Fresenius Kabi SwissBioSim - Sponsor of the study. A. Illes: Other; Employee of Fresenius Kabi SwissBioSim - Sponsor of the study. P. Baker: Other; Employee of Fresenius Kabi SwissBioSim - Sponsor of the study. J. Monnet: Other; Employee of Fresenius Kabi SwissBioSim - Sponsor of the study. J. Morais: Other; Employee of Fresenius Kabi SwissBioSim - Sponsor of the study. J. Brzezicki: None.

P117 Efficacy of filgotinib in patients with rheumatoid arthritis: Week 156 results from a long-term extension study

Abstract Background/Aims In the treatment of RA, JAK inhibitors are a valuable option to meet remission or low disease activity (LDA) treatment targets following an inadequate response (IR) or intolerance to ≥ 1 conventional synthetic disease-modifying antirheumatic drug (DMARD). FIL is a JAK1 preferential inhibitor available in two doses for the treatment of moderate to severe RA. Objectives: To evaluate long-term efficacy of two doses of FIL in clinically relevant pt populations. Methods In this interim analysis, efficacy (non-responder imputation) of FIL 200 mg (FIL200) and 100 mg (FIL100) was assessed from LTE baseline (BL) to W156 in pts with an IR to methotrexate (MTX-IR) and biologics (bDMARD-IR), enrolled from FINCH 1 (NCT02889796) and 2 (NCT02873936) parent studies (PS), respectively, receiving ≥1 FIL dose in FINCH 4 (NCT03025308). Results Study design, BL characteristics and W48 outcomes for MTX-IR1 and bDMARD-IR2 pts were reported previously. For MTX-IR and bDMARD-IR pts who received FIL200 or FIL100 in the PS, W156 remission rates using Boolean 1.0 criteria were 20.5% and 15.8%, and 18.2% and 8.9%, respectively. Adopting the Boolean 2.0 criteria slightly increased remission rates for FIL200 and FIL100 at W156: +4.2% and +4.9% for MTX-IR pts, and +1.5% and +2.4% for bDMARD-IR pts, respectively. For pts rerandomized to FIL on entering the LTE, Boolean 2.0 criteria also increased remission rates vs Boolean 1.0. Both MTX-IR and bDMARD-IR pts maintained long-term Boolean remission through W156 with FIL200 and FIL100, irrespective of prior FIL. Results for Disease Activity Score 28 with C-reactive protein (DAS28-CRP) &amp;lt;2.6, Clinical Disease Activity Index (CDAI) ≤2.8, and Simplified Disease Activity Index (SDAI) ≤3.3, and mean change from PS BL in Health Assessment Questionnaire-Disability Index (HAQ-DI) and pain are shown (Table). Similar trends in efficacy were seen for LDA and ACR response criteria. Conclusion In FINCH 4, both FIL200 and FIL100 showed sustained efficacy up to W156 in clinically relevant pt populations. Boolean 2.0 criteria classified more pts in remission, in line with the range reported in the validation study. Disclosure M.H. Buch: Consultancies; AbbVie, CESAS Medical, Galapagos, Gilead, and Pfizer (all paid to host institution). Member of speakers’ bureau; AbbVie (paid to host institution). Grants/research support; Gilead (paid to host institution). D. Aletaha: Consultancies; AbbVie, Eli Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, Sandoz, and Sanofi. Member of speakers’ bureau; AbbVie, Eli Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, Sandoz, and Sanofi. Grants/research support; AbbVie, Eli Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, Sandoz, and Sanofi. R. Caporali: Consultancies; AbbVie, Fresenius, Galapagos, Lilly, Novartis, Pfizer, and UCB. Member of speakers’ bureau; AbbVie, Amgen, BMS, Celltrion, Fresenius, Galapagos, Janssen, Lilly, Novartis, Pfizer, and UCB. B. Combe: Consultancies; AbbVie, Galapagos, Gilead, Janssen, Lilly, Novartis, and Roche-Chugai. Member of speakers’ bureau; AbbVie, Celltrion, Galapagos, Janssen, Lilly, Pfizer, and Roche-Chugai. H. Schulze-Koops: Consultancies; AbbVie, Galapagos, Lilly, and Pfizer. Member of speakers’ bureau; AbbVie, Galapagos, Lilly, and Pfizer. J. Gottenberg: Consultancies; AbbVie, BMS, Galapagos, Gilead, Lilly, MSD, Novartis, and Pfizer. Grants/research support; BMS and Pfizer. Y. Tanaka: Member of speakers’ bureau; AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, GSK, Mitsubishi-Tanabe, and Pfizer. Grants/research support; AbbVie, Asahi-Kasei Pharma, Boehringer Ingelheim, Chugai, Daiichi-Sankyo, Eisai, Takeda. R. Blanco: Consultancies; AstraZeneca, Galapagos, Janssen, Novartis, and Pfizer. Member of speakers’ bureau; AbbVie, Amgen, BMS, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, and Sanofi. Grants/research support; AbbVie and Roche. T. Takeuchi: Consultancies; AbbVie GK, Astellas, Chugai, Eli Lilly Japan, Gilead Sciences, Inc., Janssen Pharm K.K., Mitsubishi-Tanabe, and Pfizer Japan Inc. Member of speakers’ bureau; AbbVie GK, AYUMI, BMS, Chugai, Daiichi Sankyo, Eisai, Eli Lilly Japan, Gilead Sciences, Inc., Janssen Pharm K.K., Mitsubishi-Tanabe, Pfizer Japan Inc., and Sanofi K.K. Grants/research support; AbbVie GK, Asahi-Kasei Pharma, Astellas, AYUMI, Chugai, Daiichi Sankyo, Eisai, Eli Lilly Japan, Mitsubishi-Tanabe, Nippon Kayaku, and UCB Japan. E. V. Ekoka Omoruyi: Consultancies; Galapagos and Janssen. Shareholder/stock ownership; UCB. K. Van Beneden: Shareholder/stock ownership; Galapagos. Other; Employee of Galapagos. V. Rajendran: Shareholder/stock ownership; Galapagos. Other; Employee of Galapagos. C. Watson: Shareholder/stock ownership; Galapagos. Other; Employee of Galapagos. F. De Leonardis: Other; Employee of Galapagos. P. Emery: Consultancies; AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Galapagos, Gilead, Lilly, Novartis, Pfizer, Roche, and Samsung. Member of speakers’ bureau; AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Galapagos, Gilead, Lilly, Novartis, Pfizer, and Samsung. Grants/research support; AbbVie, BMS, Lilly, Novartis, Pfizer, Roche, and Samsung.

A Machine Learning Approach for Prediction of CDAI Remission with TNF Inhibitors: A Concept of Precision Medicine from the FIRST Registry.

This study aimed to develop low-cost models using machine learning approaches predicting the achievement of Clinical Disease Activity Index (CDAI) remission 6months after initiation of tumor necrosis factor inhibitors (TNFi) as primary biologic/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) for rheumatoid arthritis (RA). Data of patients with RA initiating TNFi as first b/tsDMARD after unsuccessful methotrexate treatment were collected from the FIRST registry (August 2003 to October 2022). Baseline characteristics and 6-month CDAI were collected. The analysis used various machine learning approaches including logistic regression with stepwise variable selection, decision tree, support vector machine, and lasso logistic regression (Lasso), with 48 factors accessible in routine clinical practice for the prediction model. Robustness was ensured by k-fold cross validation. Among the approaches tested, Lasso showed the advantages in predicting CDAI remission: with a mean area under the curve 0.704, sensitivity 61.7%, and specificity 69.9%. Predicted TNFi responders achieved CDAI remission at an average rate of 53.2%, while only 26.4% of predicted TNFi non-responders achieved remission. Encouragingly, the models generated relied solely on patient-reported outcomes and quantitative parameters, excluding subjective physician input. While external cohort validation is warranted for broader applicability, this study highlights the potential for a low-cost predictive model to predict CDAI remission following TNFi treatment. The approach of the study using only baseline data and 6-month CDAI measures, suggests the feasibility of establishing regional cohorts to generate low-cost models tailored to specific regions or institutions. This may facilitate the application of regional/in-house precision medicine strategies in RA management.

Are There Sex-Related Differences in the Effectiveness of Janus Kinase Inhibitors in Rheumatoid Arthritis Patients?

Background: There is evidence suggesting the existence of sex differences in the effectiveness of specific drug classes for rheumatoid arthritis (RA). Our study stands as the first to elucidate sex-related differences in the effectiveness of Janus kinase (JAK) inhibitors. Methods: The study involved 150 RA patients treated with tofacitinib, baricitinib, upadacitinib, or filgotinib between September 2017 and October 2023. Sex differences in achieving remission and low disease activity (LDA) were identified through logistic regression analyses. Sex disparities in treatment effectiveness survival were evaluated through the Kaplan-Meier estimate, employing the log-rank test for comparison. The Cox model was applied to analyze the variable sex as a potential factor that could influence the maintenance of the JAK inhibitor treatment effectiveness. Results: Concerning the achievement of remission and LDA, no differences were observed between sexes in terms of the 28-joint Disease Activity Score (DAS28) C-reactive protein (CRP), the Clinical Disease Activity Index (CDAI), and the Simplified Disease Activity Index (SDAI). With respect to the DAS28-erythrocyte sedimentation rate (ESR), female patients, compared to males, possessed 70% lower odds of achieving remission (p = 0.018) and 66% lower odds of achieving LDA (p = 0.023). No differences were observed in treatment effectiveness survival between sexes (p = 0.703). Sex was not found to influence the survival of JAK inhibitor treatment effectiveness (p = 0.704). Conclusions: Being a female or male patient does not entail differences in the effectiveness of the JAK inhibitor treatment. Our findings encourage the consideration of a global pool of composite indices (DAS28-ESR/CRP, CDAI, SDAI) to measure RA disease activity, thus individualizing the target value as advocated by the treat-to-target strategy.

Upadacitinib in Rheumatoid Arthritis and Inadequate Response to Conventional Synthetic Disease-Modifying Antirheumatic Drugs: Efficacy and Safety Through 5 Years (SELECT-NEXT).

To report 5-year efficacy and safety of upadacitinib in rheumatoid arthritis (RA) from the phase 3 long-term extension (LTE) of SELECT-NEXT. Patients on stable conventional synthetic disease-modifying antirheumatic drugs were randomized to upadacitinib 15 mg, upadacitinib 30 mg once daily (UPA15/30), or placebo for 12 weeks. Following this, placebo-randomized patients were switched to UPA15 or UPA30 in the LTE; upadacitinib-randomized patients continued their original dose. Blinding remained until dose switching from UPA30 to UPA15 due to approval of UPA15; the earliest switch occurred at week 168. Efficacy (as observed) and treatment-emergent adverse events (TEAEs) are reported through 5 years. Overall, 611 (92%) randomized patients entered the LTE; 271 (44%) discontinued study drug by 5 years, primarily due to adverse events (16%). Clinical outcomes improved or were maintained at 5 years; 51% and 43% of patients achieved Clinical Disease Activity Index remission and 75% and 66% achieved 28-joint Disease Activity Score-C-reactive protein < 2.6 among those initially randomized to UPA15 and UPA30, respectively. Proportions of patients achieving ≥ 20/50/70% improvement in American College of Rheumatology criteria responses increased from week 60 through 5 years. Results were similar regardless of initial randomization to upadacitinib or placebo. TEAEs, including TEAEs of special interest, were consistent with earlier analyses and other SELECT studies. Malignancies (excluding non-melanoma skin cancer), major adverse cardiovascular events, and venous thromboembolic events were reported infrequently. No new safety signals were observed. The 5-year benefit-risk profile for upadacitinib in RA remains favorable.

Clinical significance of anti-mutated citrullinated vimentin antibodies in rheumatoid arthritis patients.

Anti-mutated citrullinated vimentin (MCV) antibodies have recently been recommended as a better arthritis diagnostic marker. To investigate the association between anti-MCV antibodies and the clinical, functional, and radiographic characteristics of rheumatoid arthritis (RA) patients. This case-control study was conducted on 40RApatients and 40healthy subjects. All patients were subjected to an assessment of disease using the 28-joint DAS (DAS28) and Clinical Disease Activity Index (CDAI), function by HAQ-DI, physical activity by International Physical Activity Questionnaire (IPAQ), fatigue by Functional Assessment of Chronic Illness Therapy (FACIT), serological tests as well as anti-MCV Abs measurement. A plain X-ray of both hands and wrists was done. The anti-MCV Abs level was significantly higher in RA patients than in healthy controls (P< 0.001). The anti-MCV Abs had a significant positive correlation with DAS, CDAI, HAQ, RF, Anti-CCP, and CRP (P= 0.006, 0.013, 0.005, < 0.001, < 0.001and 0.041respectively) and a significant negative correlation with FACIT (p= 0.007). Positive anti-MCV RA patients had significantly higher erosions, JSN, and a total sharp score. Anti-MCV Abs may contribute to poor physical activity and more fatigue in RA patients beyond their established role in disease activity and erosion.

Effectiveness of risankizumab for the treatment of psoriatic arthritis: a multicenter, real-world study.

IL-23 inhibitors were recently approved for the treatment of skin psoriasis and psoriatic arthritis (PsA). Risankizumab, a humanized monoclonal antibody that specifically binds the p19 subunit of IL-23, has proven effective on PsA in two randomized controlled trials. To date, only a few real-world data are available on this topic. Our study aimed to prospectively evaluate the effectiveness of risankizumab in patients with PsA in a real-world setting. For this purpose, both rheumatologic and dermatologic assessments were performed at baseline and after 28-40 weeks of continuous risankizumab administration. Moreover, joint and entheses ultrasound assessment was performed at the mentioned time points. The rheumatologic assessment was carried out by means of the following scores: (i) clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA); (ii) Leeds Enthesitis Index (LEI); (iii) Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and (iii) Bath Ankylosing Spondylitis Functional Index (BASFI). The degree of skin involvement was measured by both the Psoriasis Area and Severity Index (PASI) and Physician Global Assessment (PGA). Quality of life was assessed by the Health Assessment Questionnaire (HAQ) and Dermatology Life Quality Index (DLQI). Ultrasound assessment of joints and entheses was performed on the basis of the EULAR-OMERACT score. After treatment, cDAPSA decreased from a mean value of 12.9 ± 7.6 to 7.0 ± 6.1 (P < 0.001), and the median PD score significantly decreased from baseline (3; range 1-8) to TP1 (1; range 0-7) (P < 0.001). PASI score also decreased from 8.4 ± 4.9 to 0.3 ± 0.5 (P < 0.001), and PGA from 3.1 ± 1.0 to 0.4 ± 0.5 (P < 0.001). We can conclude that risankizumab led to substantial improvement in both skin and joint involvement.

Increased epicardial adipose tissue thickness as a sign of subclinical atherosclerosis in patients with rheumatoid arthritis and ıts relationship with disease activity ındices.

Epicardial adipose tissue is a novel cardiometabolic risk factor and indicator of subclinical atherosclerosis. We aimed to evaluate the epicardial adipose tissue thickness in rheumatoid arthritis (RA) patients and its association with disease activity scores. A total of 81 rheumatoid arthritis patients and 70 age- and sex-matched healthy individuals were recruited for this cross-sectional study. Epicardial adipose tissue thickness (EATT) was measured by transthoracic two-dimensional echocardiography. Tender and swollen joint counts were recorded at the time of inclusion. The laboratory tests included erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor, anti-citrullinated protein antibodies, and serum lipid levels. Disease activity was calculated based on Disease Activity Scores for 28 joints (DAS-28) ESR and CRP, the Simple Disease Activity Index (SDAI), and the Clinical Disease Activity Index (CDAI). Epicardial adipose tissue thickness was significantly higher in the RA patients compared to the healthy controls (p < 0.001). We found statistically significant correlations of EATT with all disease activity indices (p < 0.001) and CRP (p = 0.002). According to a cut-off value of 6.4mm determined for epicardial adipose tissue thickness, the RA patients with thickness ≥ 6.4mm had higher disease activity scores and CRP levels. In the multivariable regression analysis, only SDAI score was found as an independent risk factor for increased EATT (OR, (95%CI), 13.70 (3.88-48.43), p < 0.001). Epicardial adipose tissue thickness measurement by echocardiography is a reliable method for assessing subclinical atherosclerosis in rheumatoid arthritis patients, and a higher disease activity score is an independent risk factor for coronary artery disease.

An observational study to identify causative factors for not using hydroxychloroquine in systemic lupus erythematosus

Hydroxychloroquine (HCQ) use is indicated for patients with systemic lupus erythematosus (SLE). Nevertheless, reports discussing the reasons for not prescribing HCQ are limited. We identified the factors that interfere with HCQ use in patients with SLE. This observational, single-center study included data from 265 patients with SLE in 2019. The patients were categorized into groups with and without a history of HCQ use. Between these groups, clinical characteristics were compared using univariate analysis and logistic regression models. Among the 265 patients, 133 (50.2%) had a history of HCQ use. Univariate analysis identified older age; longer disease duration; lower prednisolone dose, clinical SLE disease activity index 2000, and estimated glomerular filtration rate; higher C3 level; and lower anti-double-stranded DNA antibody concentration as HCQ non-use-related variables. Logistic regression models identified a positive association between HCQ non-use and longer disease duration (odds ratio [OR] 1.08), prednisolone dose ≤ 7.5 mg/day (OR 4.03), C3 level ≥ 73 mg/dL (OR 2.15), and attending physician having graduated > 10 years prior (OR 3.19). In conclusion, a longer disease duration, lower prednisolone dose, higher C3 level, and longer time since attending physicians’ graduation correlated with HCQ non-use. Physicians and patients should be educated to facilitate HCQ use despite these factors.

Obesity is a risk factor for poor response to treatment in early rheumatoid arthritis: a NORD-STAR study

ObjectiveThis report from the NORD-STAR (Nordic Rheumatic Diseases Strategy Trials and Registries) trial aimed to determine if obesity is associated with response to conventional and biological antirheumatic treatment in early...

Central sensitivity syndrome affects the disease activity index and treatment satisfaction in patients with rheumatoid arthritis.

Many rheumatoid arthritis (RA) patients prioritize pain improvement in treatment. As pain can result from various causes, including noninflammatory factors such as central sensitivity syndrome (CSS), we hypothesized that CSS might impact treatment satisfaction. In this cross-sectional study, we assessed the CSS effects on clinical disease activity and treatment satisfaction in RA patients. In total, 220 consecutive RA patients receiving long-term follow-up were evaluated for clinical disease activity and treatment satisfaction. CSS was evaluated using the Central Sensitization Inventory (CSI). An overall score of ≥40 indicates the presence of CSS. We queried "How satisfied are you with your treatment?"; answers included (a) very satisfied, (b) satisfied, (c) not satisfied, or (d) very dissatisfied. For univariate analysis, we condensed these answers into "dissatisfied" or "satisfied." We also evaluated treatment satisfaction using the visual analog scale (VAS), with scores ranging from 0 mm (very dissatisfied) to 100 mm (very satisfied). Of the 220 patients, 17 (7.7%) were classified as having CSS. CSI score was significantly correlated with the clinical disease activity index (CDAI; r = .322, p < .01) and treatment satisfaction (r = -.336, p < .01). Regarding treatment satisfaction, univariate analysis revealed that patient global assessment (PtGA), pain VAS, Health Assessment Questionnaire-Disability Index (HAQ-DI), Disease Activity Score in 28 joints with C-reactive protein, CDAI, and CSI scores of patients who were satisfied with treatment differed significantly from those of dissatisfied patients. Multivariate analysis revealed that CSI, PtGA, and HAQ-DI scores were associated with treatment satisfaction. In RA patients, CSS may affect the disease activity index and reduce treatment satisfaction.

Construct validity, reliability, and threshold value for treatment goals of the Thai version of the 12-item Psoriatic Arthritis Impact of Disease Questionnaire for patients with psoriatic arthritis.

To determine the construct validity, reliability, and treatment goal threshold of a Thai-language version of the 12-item Psoriatic Arthritis Impact of Disease (Thai-PsAID) questionnaire in patients with psoriatic arthritis (PsA). This cross-sectional study involved administering the proposed Thai-PsAID to 117 Thai patients with PsA. Reliability was assessed by Cronbach's α test and intraclass correlation coefficient (ICC). Construct validity was assessed using Spearman correlation with clinical disease activity index for psoriatic arthritis (cDAPSA), the Health Assessment Questionnaire (HAQ), EQ-5D index, and the patient-acceptable symptom state (PASS). The optimal cutoff score of the Thai-PsAID for minimal disease activity (MDA) was determined by receiver operating characteristic curves. Participants had a mean age of 49.5 years, 61 (52.1%) were female, and the median disease duration was 5 years. The median Thai-PsAID score was 2.1, with a Cronbach's α coefficient of .95 and an ICC of 0.77. The mean time to complete the Thai-PsAID was 2.1 min, with no missing data. The Thai-PsAID score demonstrated a moderate correlation with the cDAPSA, HAQ, and EQ-5D with indices (Spearman's rho of .64, .54, and -.55, respectively). The cutoff of 2.7 has 81%-84% sensitivity and 69%-85% specificity for classifying patients with MDA, satisfied PASS, and indicating no need to escalate medication. The Thai-PsAID is a valid, reliable, and feasible tool for measuring PsA prognosis. A cutoff of 2.7 accurately discriminates MDA and PASS and indicates no need for medication escalation. The Thai-PsAID may be used as a standalone measure.

Simplified vs modified (reduced) ultrasound 6 joint score in assessing disease activity in rheumatoid arthritis patients

Introduction and aim. With increasing ultrasound US assessment opportunities for tight rheumatoid arthritis (RA) management, more simplified accurate US-assessment is desired in clinical practice. Aim of the work is assessing modified vs simplified ultrasound 6-joint scores relevance in assessing rheumatoid arthritis disease activity. Material and methods. Fifty-five RA patients were subjected to detailed history, clinical, and musculoskeletal examination with disease activity assessment by clinical disease activity index, simple disease activity index and disease activity score in 28 joints. Com plete blood count, erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor, anti-cyclic citrullinated peptide antibodies were done. Patients underwent US examination (gray-scale and power Doppler) for wrist, 2nd and 3rd metacarpophalangeal and knee joints bilaterally. Synovitis composite score was added. Two US indices were constructed: simplified S6 and modified M6 joint scores. Results. Statistical significant positive correlations were high between S6/M6 score parameters (total, grey-scale (GS), power doppler (PD), Composite) and disease activity markers. Both M6 and S6 scores differentiated mild-moderate and moderate-severe disease activity patients. However, only S6 score differentiated remission from mild disease activity patients. Conclusion. Ultrasound 6-joint scores (especially simplified S6) were rapid, easy and sensitive ultrasound tools assessing rheu matoid arthritis disease activity in clinical practice.