Simplified Disease Activity Index Research Articles

Real-World Clinical Equivalence of Generic and Branded Tofacitinib: A Prospective Longitudinal Cohort Study in Patients With Rheumatoid Arthritis

ObjectivesTo explore the clinical efficacy and safety of generic tofacitinib vs brand name tofacitinib in patients with rheumatoid arthritis (RA) in a single-center comparative study based on a prospective real-world cohort. MethodsPatients with RA receiving tofacitinib, either generic (Kelejia) or branded (Xeljanz), from March 2017, to December 31, 2022, were enrolled. The primary outcome was the simplified disease activity index (SDAI)–defined remission rate at month 6. Secondary outcomes included the rates of remission and low disease activity defined by other composite scores; European Alliance of Associations for Rheumatology response rate, and ultrasonic synovitis scores at months 1, 3, 6, and 12. Cost-effectiveness was investigated. Propensity score–based inverse probability of treatment weighting was adopted to reduce selection bias. ResultsA total of 204 patients were enrolled: 59 in the generic group and 145 in the branded group. An SDAI-defined remission was achieved in 41.1% and 39.2% of patients in the generic and branded groups, respectively, at month 6 (P=.85). Rates of remission and low disease activity achievement, changes in clinical disease activity scores, and power Doppler and gray scale synovitis scores at months 1, 3, 6, and 12 were comparable between the 2 groups. Similar proportions of patients in the groups achieved moderate/good response at months 1, 3, 6, and 12. Rates of drug retention and adverse effects were also similar in the 2 groups. Both Kelejia and Xeljanz were cost-effective, but Kelejia had a lower average cost-effectiveness ratio. ConclusionGeneric tofacitinib (Keljia) had equivalent clinical efficacy and safety and better cost-effectiveness compared with its originator (Xeljanz).

Dynamics of clinical manifestations and cytokine levels in patients with rheumatoid arthritis associated with upadacitinib therapy

BACKGROUND: Recently, it has become evident that despite extensive data obtained from randomised placebo-controlled trials, which are still the golden standard for assessing the efficacy and safety of therapy, there are still some fundamentally important questions regarding the optimal management of patients with rheumatoid arthritis. In this regard, it is extremely relevant to assess the results of therapy in real clinical practice. Currently, much attention is paid to the study of the level of proinflammatory cytokines, both as markers of inflammatory activity of rheumatoid arthritis and monitoring the prognosis of anti-inflammatory therapy efficacy. In Russia, there are no works devoted to the study of cytokine concentration dynamics in patients with rheumatoid arthritis on the background upadacitinib therapy, which proves the relevance of the following study.
 AIM: To investigate the dynamics of clinical and laboratory values of inflammatory activity of the disease and cytokines in patients with rheumatoid arthritis associated with upadacitinib therapy.
 MATERIALS AND METHODS: We examined 10 patients with a reliable diagnosis of rheumatoid arthritis: patients’ age was 46.30 ± 10.20 years and disease duration was 12.00 (3.00–21.00) years. All the patients had moderate to high disease activity: Disease Activity Score-28 with erythrocyte sedimentation rate 5.48 (4.50–5.80), Clinical Disease Activity Index 28.00 (19.50–32.00) and Simple Disease Activity Index 29.18 (19.51–33.05). All the patients included in the study were treated with upadacitinib at a dose of 15 mg once a day against the background of the therapy with methotrexate, leflunomide, non-steroidal anti-inflammatory drugs and glucocorticoids. Observation was carried out before treatment and after 3, 6 months of therapy. Serum levels of 15 cytokines: interleukin-1β, -4, -6, -10, -17A, -17F, -21, -22, -23, -25, -31, -33, tumor necrosis factor-alpha, interferon gamma, soluble СD40 ligand were studied using multiplex xMAP technology.
 RESULTS: After 3 and 6 months of upadacitinib therapy, there was a significant decrease in Disease Activity Score-28 with erythrocyte sedimentation rate 3.78 (2.53–4.20) and 3.5 (2.00–3.68), Clinical Disease Activity Index 12.00 (5.00–17.34) and 9.0 (3.00–11.00), Simple Disease Activity Index 12.38 (5.02–17.00) and 9.61 (3.06–11.60), erythrocyte sedimentation rate 19.0 (11.0–26.0), 7.0 (4.0–18.0), CRP 0.56 (0.50–1.99), 0.71 (0.51–1.1). The values of erythrocyte sedimentation rate decreased after 3 months of treatment (baseline 21.0 (15.0–25.0) mm/hour, after 3 months 14,0 (11,0–17,0) mm/hour. After 6 months of upadacitinib therapy, there was a significant decrease in interleukin-10 (p 0.05) and interleukin-33 (p 0.01) levels compared to baseline. On the contrary, the level of interleukin-25 increased by the 6th month of treatment (p 0.01).
 CONCLUSIONS: The results of the study indicate the effectiveness of upadacitinib in rheumatoid arthritis, and also provide grounds for further study of the pathogenetic mechanisms of cytokine-dependent inflammation in this disease.

Comprehensive relationship between disease activity indices, mTSS, and mHAQ and physical function evaluation and QOL in females with rheumatoid arthritis

Rheumatoid arthritis (RA) causes significant physical disability. We comprehensively investigated the relationship between RA disease activity (Disease Activity Score 28-C-reactive protein [DAS28-CRP], Simplified Disease Activity Index [SDAI], and Clinical Disease Activity Index [CDAI]), physical function (10-Meter Walk Test [10 MWT], Timed Up and Go test [TUG], Functional Reach Test [FRT], and Disabilities of the Arm, Shoulder, and Hand [DASH]), and quality of life (QOL) (Short-Form 36 [SF-36®]). We also investigated the relationship between van der Heijde’s modified Total Sharp Score (mTSS), modified Health Assessment Questionnaire (mHAQ), and physical function and QOL assessments. Among 35 female patients with RA, DAS28-CRP correlated solely with DASH (r = 0.376), while SDAI and CDAI did not correlate with physical function. The mTSS-hand roentgenographic evaluation correlated with TUG (r = 0.359), FRT (r = − 0.415), and DASH (r = 0.533) among physical function assessments. The mHAQ correlated with 10 MWT (r = 0.347), TUG (r = 0.356), FRT (r = − 0.420), and DASH (r = 0.646). DAS28-CRP correlated with six of the eight subscales of SF-36®, and mTSS and mHAQ correlated with only one subscale. RA disease activity assessments may not reflect all physical functions and QOL domains of female patients with RA. Evaluating physical function and QOL in female patients with RA is essential.

Effectiveness and safety of treat-to-target strategy for methotrexate-naïve rheumatoid arthritis patients >75 years of age.

To identify differences in effectiveness and safety of a treat-to-target (T2T) strategy comparing late-onset MTX-naïve RA patients (LORA) ≥75 or <75 years of age. Treatment was adjusted to target low disease activity with conventional synthetic DMARDs followed by biologic DMARDs (bDMARDs) in LORA ≥75 years (n = 98, mean age 80.0 years) and LORA <75 years (n = 99) with moderate-high disease activity. Achievement of Simplified Disease Activity Index (SDAI) remission at week 156 by non-responder imputation analysis was evaluated as a primary outcome. LORA ≥75 years had more comorbidities than LORA <75 years, but SDAI and ACPA positivity were similar at baseline. Of the LORA ≥75 years, 70.4% started MTX and 34.1% and 37.1% received a bDMARD at week 52 and 156, respectively (very similar to the LORA <75 years). Glucocorticoid use was more frequent in the LORA ≥75 years than in the LORA <75 years. Comorbidities/adverse events more frequently contributed to the reasons for non-adherence to T2T in the LORA ≥75 than in the LORA <75. At week 156, 32.7% of the LORA ≥75 and 66.7% of the LORA <75 achieved SDAI remission (P < 0.001). The cumulative incidence of serious adverse events (SAEs) over 156 weeks was 42.8% in the LORA ≥75 and 22.1% in the LORA <75. Multivariable analysis indicated an increased risk of SDAI non-remission at week 156 in the LORA ≥75 [odds ratio 2.82 (95% CI 1.29. 6.14)] after adjusting for comorbidities at baseline, non-adherence to T2T and SAEs. It was more difficult to achieve remission in the LORA ≥75 patients than in the LORA <75 patients due to both poor treatment response and safety issues.

Metabolic Syndrome and Rheumatoid Arthritis Activity: An Analysis of Clinical, Laboratory, and Ultrasound Parameters.

(1) Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease associated with an increased incidence of metabolic syndrome (MetS). The aim of this study was to determine if there is an association between MetS and parameters of RA activity, as well as between metabolic parameters and indices of RA activity. (2) Methods: This study involved 65 patients with RA. MetS was diagnosed according to the 2009 IDF/AHA/NHLBI criteria. The comparative analysis was conducted between RA patients with MetS (RA (MetS (+)) and without MetS (RA (MetS (-)). The activity of RA was assessed using clinical, laboratory, and ultrasound (US) parameters. (3) Results: Compared with RA MetS (-) patients, RA MetS (+) patients were characterized by higher disease activity, according to Disease Activity Score (DAS28), Simplified Disease Activity Index (SDAI), and Clinical Disease Activity Index (CDAI). RA MetS (+) patients had significantly higher tender and swollen joint counts, and values of erythrocyte sedimentation rate, C-reactive protein, and US parameters (grey-scale (GSUS), power Doppler (PDUS)). Significant correlations were found between metabolic parameters (waist circumference, cholesterol and glucose concentrations) and indices of RA activity. (4) Conclusion: The results of this study show that, in patients with RA, the presence of MetS is associated with higher disease activity, based on several clinical, laboratory, and US parameters.

Abstract 5 — Prediction of Flare Following Glucocorticoids Withdrawal in Rheumatoid Arthritis Patients with Continuation of csDMARDs: A Real-Life Study

Background In patients with rheumatoid arthritis (RA), glucocorticoids (GC) should be firstly discontinued before considering tapering conventional synthetic disease-modifying anti-rheumatic drugs (csDMARD) or other biological agents. We aim to determine risk factors for flare after GC withdrawal in RA patients undergoing csDMARDs. Method RA patients who discontinued GC with continuation of csDMARD were selected from a longitudinal real-world cohort. Established RA was defined as disease duration over 12 months. Dissatisfied RA control was defined as the proportion of simplified disease activity index (SDAI)-based remission time to total time from GC initiation to discontinuation less than 50%. Logistic regression was used to analyze the independent risk factors for flare after GC discontinuation and results were expressed as odds ratio (OR). Results There were 115 eligible RA patients discounted GC with continuation of csDMARDs (methotrexate: 80%; hydroxychloroquine: 61%; csDMARDs combination: 79%). Of these, 24 patients experienced flare after GC discontinuation. Compared with relapse-free patients, flare patients were more likely to have established RA (75% vs. 49%, p=0.025), higher median cumulative prednisolone dosages (3.3g vs. 2.2g, p=0.004), and higher proportion of dissatisfied RA control during GC usage (66% vs. 33%, p=0.038). In multivariate analysis, significantly increased flare risk was predicted by established RA (OR 2.93 [1.02-8.43]), cumulative prednisolone dose &gt; 2.5g (OR 3.69 [1.34-10.19]) and dissatisfied RA control (OR 3.00 [1.09-8.30]). Flare risk was increased with increases in number of risk factors, with highest OR of 11.56 in patients with three risk factors (p for trend=0.002). Conclusions Flare following GC withdrawal is not common in RA patients with undergoing csDMARDs therapy. Established RA, higher cumulative GC dose and dissatisfied RA control before GC discontinuation are important factors associated with flare after GC withdrawal.

Ten-year radiographic and functional outcomes in rheumatoid arthritis patients in remission compared to patients in low disease activity

BackgroundTo compare the 10-year structural and functional prognosis between patients in sustained remission versus patients in sustained low disease activity (LDA) in early rheumatoid arthritis (RA).MethodsWe included 256 patients from the ESPOIR cohort who fulfilled the 2010 ACR/EULAR criteria for RA and who were in sustained remission using the Simple Disease Activity Index (SDAI) score (n = 48), in sustained LDA (n = 139) or in sustained moderate to high disease activity (MDA or HDA, n = 69) over 10 years. The mTSSs progression over 10 years and the 10-year HAQ-DI scores were compared between the 3 groups. A longitudinal latent process mixed model was used to assess the independent effect of SDAI status over time on 10-year mTSS progression and HAQ-DI at 10 years.ResultsPatients in sustained remission group were younger, had lower baseline HAQ-DI and mTSS scores and were less exposed to glucocorticoids, methotrexate or biologic disease-modifying anti-rheumatic drugs over 10 years. Patients in sustained remission had lower 10-year structural progression (variation of mTSS in the remission group: 4.06 (± 4.75) versus 14.59 (± 19.76) in the LDA group and 21.04 (± 24.08), p < 0.001 in the MDA or HDA groups) and lower 10-year HAQ-DI scores (10-year HAQ-DI in the remission group: 0.14 (± 0.33) versus 0.53 (± 0.49) in the LDA group and 1.20 (± 0.62) in the MDA or HDA groups, p < 0.001). The incidence of serious adverse events over 10 years was low, about 3.34/100 patient years, without any difference between the three groups.ConclusionRA patients in sustained SDAI remission have better long-term structural and functional outcomes in comparison to patients in sustained LDA.

Adipokines in rheumatoid arthritis patients suffering glomerulonephritis

Background: Beside their eminent role in metabolic syndrome, white adipose tissue (WAT) derived adipokines might have a distinguished role in autoimmune and rheumatic diseases. In addition, increased level of many adipokines is observed in patients suffering glomerulonephritis. The status of adipokines was not studied in rheumatoid arthritis patients (RA) suffering glomerulonephritis (GN). Objective: To study serum level of adiponectin, leptin, and Visfatin in RA patients suffering GN in a trial to elucidate if they play a role on metabolic or endothelial function. Cases and methods: In this cross-sectional case control observational study, we compared serum level of adiponectin, leptin, and Visfatin in fifty RA patients (group I) in coparison to fifty RA cases suffering chronic GN (group II) and fifty normal control subjects. In addition, we looked for kidney function tests and 24 urine protein (UP), serum calcium, phosphorus, alkaline phosphatase (AP), 25 hydroxy vitamin D (25 OH vit. D), parathyroid hormone (PTH), C-reactive protein (CRP), interleukin 6(IL6), lipid profile, and Homa insulin resistanc (Homa IR). RA cases were further investigated for rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) carotid arteries intima media thickness (IMT), brachial artery flow mediated Dilation (BA-FMD), health assessment questionnaire (HAQ), disease activity score calculator (DASC), simple disease activity index (SDAI), and clinical disease activity index (CDAI). Percutaneous kidney biopsies were obtained in group II patients. Results: Serum adiponectin and Visfatin are significantly higher and serum leptin is significantly lower in Group II compared to group I and the control group (20.3 vs. 18.6 and 12.3, 24,5 vs. 20.9 and 9.8, and 3.6 vs. 4.6 and 7.8 ng/mL for median serum adiponectin, visfatin, and leptin in group II vs group I and control group respectively, P&lt;0.001 in all). Serum level of 25 (OH) vit D is significantly lower, while serum AP, PTH and Homa IR are significantly higher in group I compared to control subjects (18 vs. 37 ng/mL, 140.5 vs, 57 u/L, 63 vs 47.8 ng/mL, and 13.2 vs 4 respectively, P&lt;0.001 in all) whilst there is no significant difference in these parameters between the RA groups. BA-FMD is significantly lower in group II vs group I (3% vs 4%, P=0.02) but there are no significant differences between these two groups in IMT of carotid arteries, HAQ, DASC, SDAI or CDAI. Moreover, there is no difference in any of the studied parameters within patients of group II according to renal histopathology. Conclusion: Studied adipokines have no relation to metabolic or vascular complications of RA. Changes of serum adipokines in GN patients are unrelated to inflammation. This pilot study would stimulate further research looking for the possible role of different adipokines in GN complicating RA.

Definition of follicular helper T cell and cytokines expression in synovial fluid of rheumatoid arthritis.

This study aimed to assess the role of synovial fluid (SF) CD4+T, CD19+B, follicular helper cells (Tfh), and cytokines in the pathogenesis of rheumatoid arthritis (RA). This study enrolled 16 patients with RA and 8 patients with osteoarthritis (OA). The frequencies of the SF CD4+ T, CD19+ B, Tfh cells, and Tfh subsets were assessed using flow cytometry. The medical condition in patients with RA was evaluated using The Disease Activity Score 28 (DAS28), the Clinical Disease Activity Index (CDAI), and the Simplified Disease Activity Index (SDAI). Levels of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), anti-cyclic citrullinated peptide (anti-CCP), and rheumatoid factor (RF) were measured. The cytokines IL-4, IL-13, IL-21, and BLyS were measured by ELISA test. The percentages of SF CD4+T, CD19+B, and PD-1+CXCR5+ Tfh in RA patients were higher than those in OA patients. And the Tfh2 was the main subset among Tfh subsets. In addition, levels of IL-21 and BLyS were higher in patients with RA compared to patients with OA. Furthermore, the treatment of TNF-α inhibitors may be associated with decreased levels of SF Tfh. Elevated SF Tfh, B cell, and cytokines expression profiles were observed in RA patients. Tfh2 was the major subset of the Tfh, and IL-21 and BLyS were significantly enhanced. Additionally, TNF-α inhibitors reduced Tfh in SF. Therefore, Tfh, B, and Tfh2 cells could play a significant role in the progression of RA. Key Points •Tfh cells in the synovial fluid are significantly higher in RA patients and are dominated by the Tfh2 subpopulation. •Synovial fluid Tfh cells decrease in RA patients after anti-TNF-α treatment.

Effectiveness of a treat-to-target strategy in patients with moderate to severely active rheumatoid arthritis treated with abatacept

BackgroundTo compare a treat-to-target (T2T) approach and routine care (RC) in adults with active to severely active rheumatoid arthritis (RA) initiating subcutaneous abatacept.MethodsA 12-month cluster-randomized trial in active RA patients treated with abatacept was conducted. Physicians were randomized to RC or T2T with a primary endpoint of achieving sustained Clinical Disease Activity Index (CDAI) low disease activity (LDA) at two consecutive assessments approximately 3 months apart. Additional outcomes included Simple Disease Activity Index (SDAI), Disease Activity Score 28-CRP (DAS28-CRP), Routine Assessment of Patient Index Data 3 (RAPID3), and the Health Assessment Questionnaire-Disability Index (HAQ-DI). Time to achieve therapeutic endpoints was assessed with survival analysis.ResultsAmong the 284 enrolled patients, 130 were in the T2T group and 154 in RC. Primary endpoint was achieved by 36.9% and 40.3% of patients in T2T and RC groups, respectively. No significant between-group differences were observed in the odds of achieving secondary outcomes, except for a higher likelihood of CDAI LDA in the T2T group vs. RC (odds ratio [95% confidence interval]: 1.33 [1.03–1.71], p = 0.0263). Compared with RC, patients in the T2T group achieved SDAI remission significantly faster (Kaplan–Meier-estimated mean [standard error]: 14.0 [0.6] vs. 19.3 [0.8] months, p = 0.0428) with a trend toward faster achievement of CDAI LDA/remission, DAS28-CRP remission, and HAQ-DI minimum clinically important difference.ConclusionsPatients managed per T2T and those under RC experienced significant improvements in RA disease activity at 12 months of abatacept treatment. T2T was associated with higher odds of CDAI LDA and a shorter time to achieving therapeutic endpoints.Trial registrationName of the registry: ClinicalTrials.gov.Trial registrations: NCT03274141.Date of registration: September 6, 2017.

Systematic Literature Review of Real-World Evidence on Baricitinib for the Treatment of Rheumatoid Arthritis.

Baricitinib, an orally available small-molecule inhibitor of Janus kinase (JAK)1 and JAK2, is indicated to treat active moderate-to-severe rheumatoid arthritis (RA). This systematic review described the real-world clinical characteristics of baricitinib-treated patients with RA, prescription patterns, effectiveness, drug persistence, patient-reported outcomes (PROs; physical function, pain, health-related quality of life [HRQoL]), patient global assessment (PGA), and safety of baricitinib. A PRISMA systematic review of real-world studies was conducted to identify relevant literature published between January 2016 and September 2022 using MEDLINE®, EMBASE®, and evidence-based medicine review databases. Websites or online repositories of the American College of Rheumatology and the European Alliance of Associations for Rheumatology were searched manually to include relevant abstracts from conferences held between January 2016 and November 2022. A total of 11,472 records were identified by searching online databases. Seventy studies were included in the study, of which 40 were abstracts. Most patients were older (51-71 years), female, and with mean RA duration of 4-19 years. Baricitinib was mostly used after the failure of one or more bDMARDs, and 4 mg dosing was prevalent in patients with RA (range 22-100%). Clinical effectiveness of baricitinib was reported in real-world settings regardless of prior biologic/targeted synthetic disease-modifying antirheumatic drug (DMARD) use and concomitant conventional synthetic DMARD use. Achievement of Clinical Disease Activity Index (CDAI) remission was reported in 8.7-60% of patients at week 12 and CDAI low disease activity (LDA) in 20.2-81.6% at week 24. The proportion of patients attaining Simple Disease Activity Index (SDAI) remission was reported in 12% at week 4 to 45.4% at 24 weeks. Drug persistence was high, similar, or equal to anti-tumor necrosis factor drugs. No new safety signals were identified. Baricitinib demonstrated effectiveness in the real-world setting with a consistent safety profile observed in clinical studies. Better persistence rates for baricitinib compared to bDMARDs with improvement in PROs were reported, although baricitinib-treated patients had RA with poor prognostic characteristics.

Carriers of HLA-DRB1*04:05 have a better clinical response to abatacept in rheumatoid arthritis

HLA-DRB1 shared epitope risk alleles are the strongest genetic risk factors for rheumatoid arthritis (RA) and potential biomarkers for treatment response to biological disease-modifying antirheumatic drugs (bDMARDs). This study aimed to investigate the association between treatment response and individual HLA-DRB1 alleles in RA patients receiving different bDMARDs. We recruited 106 patients with active RA who had started abatacept, tocilizumab, or TNF inhibitors as a first-line bDMARDs. We examined the relationship between Simplified Disease Activity Index (SDAI) improvement at 3 months and HLA-DRB1 allele carriage. The results revealed that the HLA-DRB1*04:05 allele, a shared-epitope allele, was significantly associated with better SDAI improvement only after abatacept treatment (SDAI improvement 28.5% without the allele vs 59.8% with allele, p = 0.003). However, no significant association was found with other treatments. Both multivariate linear regression and mediation analysis confirmed that the HLA-DRB1*04:05 allele was independently associated with abatacept treatment response, regardless of anti-CCP antibody titers. The study concluded that in patients with RA receiving their first-line bDMARD treatment, carrying the HLA-DRB1*04:05 allele was associated with better SDAI improvement specifically in abatacept-treated patients. These disease-risk HLA alleles have the potential to serve as genomic biomarkers for predicting treatment response with co-stimulation blockage therapy.

An engineered glove to follow finger function in rheumatoid arthritis: an observational prospective study

The engineered Hand Test System (HTS) glove has shown high reliability in assessing the baseline functional status of rheumatoid arthritis (RA) hand. Starting from this achievement, the aim of the present observational prospective study was to assess the functionality of the single fingers of rheumatoid hand at follow-up. Eighty RA patients performed HTS glove tests at baseline and among these fifty-six patients were re-tested after 7 months. The HTS glove parameters [Touch Duration (TD), Movement Rate (MR), Inter Tapping Interval (ITI)] were correlated with disease activity and disability clinimetric indexes [Disease Activity Score 28 joint count—C-reactive protein (DAS28-CRP), Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI), Health Assessment Questionnaire—Disability Index (HAQ-DI), grip strength, visual analogue scale of pain (VAS), patient global assessment (PGA)], and with laboratory values. HTS glove parameters (TD, ITI, and MR) showed statistically significant correlations with clinimetric and clinical indexes at both time points (p < 0.05). During follow-up, a statistically significant variation of all HTS glove parameters for the fingers that have performed both the worst or best HTS test at baseline was detected (p < 0.05), while the mean HTS glove parameter values by considering all fingers did not show a statistically significant variation over time, as well as the traditional clinimetric indexes. Besides the objective role in assessing the RA hand function by integrating the traditional clinimetric indexes, the HTS glove seems a useful tool for evaluating worst or best finger function during time by measuring the movement speed.

Correlation of Disease Activity Scores and Routine Assessment of Patient Index Data (RAPID3) on a Multidimensional Health Assessment Questionnaire in Patients With Rheumatoid Arthritis: A Saudi Experience.

Introduction This study aimed to analyze the correlation between Routine Assessment of Patient Index Data (RAPID3) and disease activity scores using the Disease Activity Score 28 (DAS28 erythrocyte sedimentation rate (ESR)/C-reactive protein (CRP)), Clinical Disease Activity Index (CDAI), and Simplified Disease Activity Index (SDAI) in patients with rheumatoid arthritis (RA) attending a single rheumatology center in Jeddah. Methods A cross-sectional study of patients with RA who fulfilled the 2010 American College of Rheumatology criteria for the diagnosis of RAbetween June 2018 and November 2019 was conducted. The validated Arabic version of the multidimensional health assessment questionnaire (MDHAQ) was used. The data collected included demographic information, comorbid illnesses, concomitant medications, laboratory results, and disease activity measured using the DAS 28 ESR/CRP, CDAI, SDAI, and RAPID3. Results A total of 137 patients with RA were included in the analysis; the mean age was 53.1 (± 12) years, there were 122 (89%) females, and the mean disease duration was 8 (± 4) years. Forty-nine (44.5%) patients were treated with anti-tumor necrosis factor (anti-TNF), 53 (48.2%) with non-anti-TNF, 8 (7.3%) with Janus kinase (JAK) inhibitors, and 27 (20%) with synthetic disease-modifying drugs (sDMARD). The mean RAPID3 (0-10) score was 3.6 (± 2) for low disease activity. The mean DAS28 ESR was 4.16 (± 4) for moderate disease activity. The mean DAS CRP was 3.39 (± 1.2) for moderate disease activity. The mean CDAI was 13.4 (± 10.7) for moderate disease activity. The mean SDAI was 15.34 (± 11.8) for moderate disease activity. Pearson's correlations showed a strong correlation with DAS28 CRP (r=0.773, p < 0.001), SDAI (r=0.764,p < 0.001), CDAI (r=0.710, p < 0.001), and DAS28 ESR (r=0.283, p < 0.002). Conclusion RAPID3significantly correlated with DAS28-CRP, SDAI, and CDAI scores in our patients. It isa simple, inexpensive, and patient-centered practical tool for assessing disease activity that can reflect the health-related quality of life and be easily implemented inclinical practice.

Remission, response, retention and persistence to treatment with disease-modifying agents in patients with rheumatoid arthritis: a study of harmonised Swedish, Danish and Norwegian cohorts

ObjectivePrecision medicine in rheumatoid arthritis (RA) requires a good understanding of treatment outcomes and often collaborative efforts that call for data harmonisation. We aimed to describe how harmonisation across study...

Dynamics of clinical manifestations and cytokine concentrations in patients with rheumatoid arthritis on olokizumab therapy

The aim of the study was to investigate the dynamics of clinical and laboratory parameters of inflammatory disease activity and cytokines in patients with rheumatoid arthritis (RA) against the background of olokizumab (OKZ) treatment.Materials and methods. Ten patients with a reliable diagnosis of RA were examined: patients’ age was 46.00 (30.00; 60.00) years, duration of disease was 9.0 (3.0; 12,0) years. All patients had moderate to high disease activity: DAS28-ESR (Disease Activity Score 28 with Erythrocyte Sedimentation Rate) – 513 (4.34; 5,80); CDAI (Clinical Disease Activity Index) – 30.00 (24.00; 35.00); SDAI (Simplified Disease Activity Index) – 31.86 (24.36; 38.59). All patients were treated with OKZ at a dose of 64 mg subcutaneously every 4 weeks on the background of therapy with methotrexate, leflunomide, nonsteroidal anti-inflammatory drugs, and glucocorticoids. Observations were performed before treatment and after 3, 6 months of therapy. Serum levels of 15 cytokines: interleukin (IL) 1β, IL-4, IL-6, tumor necrosis factor α (TNF-α), interferon (INF) γ, IL-10, IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, sCD40L, – were examined using multiplex xMAR technology.Results. After 3 and 6 months of OKZ therapy, there was a significant decrease in DAS28-ESR of 3.53 (2.83; 4.26) and 3.48 (2.8; 4.10); CDAI – 11.00 (6.0; 16.00) and 10.0 (5.0; 15.0); SDAI – 10.0 (5.0; 15.0) and 10.17 (7.02; 15.02); C-reactive protein (CRP) concentrations (initial – 14.30 (7.00; 24.70) mg/l, after 3 months – 0.70 (0.40; 0.90) mg/l and after 6 months – 0.65 (0.20; 3.00) mg/l). After 3 months of treatment we found an increase in IL-6 concentration (initial – 1.89 (1.61; 2.33) pg/ml and 89.98 (35.09; 165.84) pg/ml; p&lt;0.01), after 6 months – its level decreased to 44.88 (5.25; 80.90) pg/ml without reaching, however, the initial values (p&lt;0.05). Against the background of OCZ, after 3 months of treatment there was an increase in IL-25 concentration (p&lt;0.01), and after 6 months of therapy – TNF-α (p&lt;0.05).Conclusion. The use of OKZ leads to an increase in the concentration of total IL-6 in the blood serum of RA patients, while the clinical and laboratory activity of the disease decreases.

Does Pizza Consumption Favor an Improved Disease Activity in Rheumatoid Arthritis?

To our knowledge, no studies so far have investigated the role of pizza and its ingredients in modulating disease activity in rheumatoid arthritis (RA). We assessed this question via a recent cross-sectional study including 365 participants from Italy, the birthplace of pizza. Multiple robust linear and logistic regression models were fitted with the tertile consumption categories of each available pizza-related food item/group (i.e., pizza, refined grains, mozzarella cheese, and olive oil) as independent variables, and each available RA activity measure (i.e., the Disease Activity Score on 28 joints with C-reactive protein (DAS28-CRP), and the Simplified Disease Activity Index (SDAI)) as the dependent variable. Stratified analyses were carried out according to the disease severity or duration. Participants eating half a pizza >1 time/week (vs. ≤2 times/month) reported beneficial effects on disease activity, with the significant reductions of ~70% (overall analysis), and 80% (the more severe stratum), and the significant beta coefficients of -0.70 for the DAS28-CRP, and -3.6 for the SDAI (overall analysis) and of -1.10 and -5.30 (in long-standing and more severe RA, respectively). Among the pizza-related food items/groups, mozzarella cheese and olive oil showed beneficial effects, especially in the more severe stratum. Future cohort studies are needed to confirm this beneficial effect of pizza and related food items/groups on RA disease activity.

Effectiveness and safety of filgotinib in rheumatoid arthritis: a real-life multicentre experience.

We investigated the effectiveness and safety of filgotinib in a real-life multicentre cohort of rheumatoid arthritis (RA) patients. RA patients were evaluated at baseline and after 12 and 24 weeks and were stratified based on previous treatments as biologic disease-modifying anti-rheumatic drug (bDMARD)-naive and bDMARD-insufficient responders (IR). Concomitant usage of methotrexate (MTX) and oral glucocorticoids (GC) was recorded. At each timepoint we recorded disease activity, laboratory parameters and adverse events. 126 patients were enrolled. 15.8% were bDMARD-naive (G0), while 84% were bDMARD-IR (G1). In G0, 45% of patients were in monotherapy (G2) and 55% were taken MTX (G3). In G1, 50% of patients were in monotherapy (G4) and 50% used MTX (G5).A significant reduction in all parameters at 12 weeks was observed; in the extension to 24 weeks the significant reduction was maintained for patient global assessment (PGA), examiner global assessment (EGA), visual analogue scale (VAS) pain, VAS fatigue, disease activity score (DAS)28- C-reactive protein (CRP) and CRP values. Filgotinib in monotherapy showed better outcomes in bDMARD-naive patients, with significant differences for patient reported outcomes (PROs) and DAS28-CRP. At 12 weeks, low disease activity (LDA) and remission were achieved in a percentage of 37.2 % and 10.7 % by simplified disease activity index (SDAI), 42.6 % and 5.7 % by clinical disease activity index (CDAI), 26.8 % and 25.2 % by DAS28-CRP, respectively. A significant decrease in steroid dose was evidenced in all patients. We observed a major adverse cardiovascular event in one patient and an increase in transaminase in another. No infections from Herpes Zoster were reported. Our real-world data confirm the effectiveness and safety of filgotinib in the management of RA, especially in bDMARD-naive patients.

Disease activity and disease-related factors are drivers of patient global assessment in rheumatoid arthritis: a real-life cross-sectional study

Despite that the Patient Global Assessment (PGA) is widely used for measuring Rheumatoid Arthritis (RA) disease activity to define the remission state of the disease, the primary contributors influencing patients’ ratings are still debated. This study aims to determine which clinical, sociodemographic and lifestyle-related contextual factors might be key drivers of PGA in RA. This single-center cross-sectional study recruited 393 consecutive adult RA patients. Median age 60 years, females 306 (77.9%). Data related to disease activity were assessed by using Simplified Disease Activity Index (SDAI), severity by Health Assessment Questionnaire (HAQ), and impact by RA Impact of Disease (RAID). Sociodemographic/lifestyle features were collected. Disease remission was calculated using Boolean-based criteria 1.0 and 2.0. Quantile regression models were used for univariate and multivariate analysis. The remission rate progressively increased from 15% by using SDAI with a Boolean 1.0-based definition to 43.5% using a Boolean 2.0-based remission. Among factors related to disease activity, the use of low-dose corticosteroids, the RAID items pain and sleep difficulties were predictive for worse PGA scores (p = 0.01). Among factors related to disease severity HAQ score and RAID total were independent factors associated with higher median PGA (p = 0.02 and p < 0.001). RAID’s physical well-being was related to PGA scores (p = 0.01). An increasing trend in PGA was observed in longstanding diseases (> 15 years). Our results confirmed that there is no unambiguous interpretation of the PGA score. It is a measure related to some disease activity parameters, but it is also influenced by contextual factors related to disease severity and impact. These data highlighted that PGA should have a broad interpretation, thus supporting the proposal of a dual targets (biological and impact) approach to obtain a more accurate estimate of disease activity.

Prediction of flare following glucocorticoids withdrawal in rheumatoid arthritis patients with continuation of csDMARDs: a real-life study.

To determine the risk factors for flare after glucocorticoids (GC) withdrawal in rheumatoid arthritis (RA) patients with undergoing conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). RA patients who discontinued GC with continuation of csDMARD were selected from a longitudinal real-world cohort. Established RA was defined as disease duration over 12months. Dissatisfied RA control was defined as the proportion of simplified disease activity index (SDAI)-based remission time to total time from GC initiation to discontinuation less than 50%. Logistic regression was used to analyze the independent risk factors for flare after GC discontinuation and results were expressed as odds ratio (OR). There were 115 eligible RA patients discounted GC with continuation of csDMARDs (methotrexate: 80%; hydroxychloroquine: 61%; csDMARDs combination: 79%). Of these, 24 patients experienced flare after GC discontinuation. Compared with relapse-free patients, flare patients were more likely to have established RA (75% vs 49%, p = 0.025), higher median cumulative prednisolone dosages (3.3 vs 2.2g, p = 0.004), and higher proportion of dissatisfied RA control during GC usage (66% vs 33%, p = 0.038). In multivariate analysis, significantly increased flare risk was predicted by established RA (OR 2.93 [1.02-8.43]), cumulative prednisolone dose > 2.5g (OR 3.69 [1.34-10.19]) and dissatisfied RA control (OR 3.00 [1.09-8.30]). Flare risk was increased with increases in number of risk factors with highest OR of 11.56 in patients with three risk factors (p for trend = 0.002). Flare following GC withdrawal is not common in RA patients with undergoing csDMARDs therapy. Established RA, higher cumulative GC dose and dissatisfied RA control before GC discontinuation are important factors associated with flare after GC withdrawal.