Rheumatoid Arthritis In Clinical Practice Research Articles

Mitochondrial DNA copy number and the risk of autoimmune diseases: A Mendelian randomization study with meta-analysis

BackgroundMitochondrial DNA plays a crucial role in the pathophysiology of autoimmune diseases (ADs). However, the association between mitochondrial DNA copy number (mtDNA-CN) and ADs risk is controversial. In this study, Mendelian randomization (MR) analysis and meta-analysis were performed using three sets of independent instrumental variables (IVs) to investigate the potential association between mtDNA-CN and 20 types of ADs. MethodsThe three sets of IVs were drawn primarily from participants in the UK Biobank and the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium using different methods. Outcome data for ADs were investigated using summary statistics from the FinnGen cohort. The potential causal associations were assessed using inverse-variance weighting (IVW), MR-Egger, and weighted median methods. Sensitivity analysis and the Steiger test were used to verify the robustness of the MR estimates. In addition, a meta-analysis was conducted to pool the results from three IV groups. ResultsOverall, genetically predicted mtDNA-CN was not associated with ADs risk (OR = 1.046, 95 % CI: 0.964–1.135, P = 0.283). However, subgroup analyses showed positive causal associations of mtDNA-CN with autoimmune hypothyroidism (OR = 1.133, 95 % CI: 1.016–1.262, P = 0.024) and rheumatoid arthritis (OR = 1.219, 95 % CI: 1.028–1.445, P = 0.023). In contrast, there was no causal association between mtDNA-CN and atopic dermatitis as well as psoriasis, ulcerative colitis, adult-onset Still disease, type1 diabetes, Crohn disease, sarcoidosis, ankylosing spondylitis, multiple sclerosis, autoimmune hyperthyroidism, primary sclerosing cholangitis, systemic lupus erythematosus, systemic sclerosis, alopecia areata, myasthenia gravis, Guillain-Barre syndrome, dermatopolymyositis, and vitiligo. ConclusionsThis MR analysis showed mtDNA-CN is causally associated with an increased risk of autoimmune hypothyroidism and rheumatoid arthritis at the genetic level. The findings have important implications for the use of mtDNA-CN as a biomarker for risk assessment of autoimmune hypothyroidism and rheumatoid arthritis in clinical practice.

Challenges in implementing treat-to-target in rheumatoid arthritis: a perspective from Brazilian rheumatologists

BackgroundPatient management in rheumatoid arthritis (RA) has evolved to a “treat-to-target” (T2T) approach, which entails intensive treatment and regular follow-up with the goal of achieving low levels of disease activity or clinical remission. Even though a T2T approach is endorsed by professional organizations and yields superior outcomes, its implementation remains incomplete. EVEREST (EleVatE care in RhEumatoid arthritiS with Treat-to-target) is a quality-improvement initiative designed to improve the widespread implementation of a personalized T2T strategy and enable patients with RA to reach their full potential for remission. We describe the Brazilian results from the Global T2T Survey, first part of the EVEREST program.MethodsBetween June and September 2022, we conducted an online survey targeting rheumatologists in Brazil. Our objective was to evaluate the barriers and knowledge gaps hindering the effective implementation of T2T strategies. To achieve this, we employed a set of multiple-choice questions specifically crafted to elicit responses categorized in a structured order.Results166 rheumatologists participated in the survey, 51% of them with more than 21 years of experience in rheumatology. Regarding the perceived challenges in the management of RA in clinical practice, the highest percentage of agreement/strong agreement among the participants was related to the contradictory results of disease activity measures (60%). In terms of the main barriers to assess the disease activity in clinical practice, the lack of adherence to treatment and contradictory assessments between patient-reported outcomes and composite measures were indicated by 75% and 59% of the participants, respectively, as a moderate/serious barrier. The most frequently knowledge and skill gaps related to the management of RA pointed out by the participants were on the difficulty to assess patients’ health literacy (54% stated to have no more than intermediate knowledge on standardized methods to assess it and 43% no more than intermediate skills on determining the level of health literacy of the patients). In general, the use of tools to support the management of RA patients in clinical practice was indicated to be unusual by the participants. Self-reflection questionnaires, patient education materials and treatment consideration checklists were pointed out as the least frequently used tools (85%, 64% and 62% of the participants stated to use them never, rarely, or only sometimes, respectively).ConclusionsOur findings indicate a greater need for design, selection, and uptake of practical strategies to further improve communication between healthcare providers and patients with RA, as well as for promoting well-informed, collaborative decision-making in their care.

HSD122 Medication Adherence, Persistence, and Treatment Switching in Patients Receiving Advanced Therapies for Rheumatoid Arthritis in Clinical Practice

HSD122 Medication Adherence, Persistence, and Treatment Switching in Patients Receiving Advanced Therapies for Rheumatoid Arthritis in Clinical Practice

One-Year Medication Adherence and Persistence in Rheumatoid Arthritis in Clinical Practice: A Retrospective Analysis of Upadacitinib, Adalimumab, Baricitinib, and Tofacitinib.

This study evaluated 12months adherence and persistence among Janus kinase inhibitors (upadacitinib, baricitinib, tofacitinib) and adalimumab, a tumor necrosis factor inhibitor (TNFi), in patients with rheumatoid arthritis (RA). This retrospective analysis used administrative claims data from the Merative™ MarketScan® Research Databases (2018-2022). Eligible adults had≥1 RA diagnosis before the index date,≥1 pharmacy claim for index medication, and≥12months of continuous insurance enrollment pre- and post-index. Adherence to treatment [defined as proportion of days covered (PDC)≥80%], risk of treatment discontinuation, and mean time to discontinuation were assessed during the 12months follow-up. Adjusted odds ratios (aOR), adjusted hazard ratios (aHR), and 95% confidence intervals (CI) were reported. In total, 6317 patients were included (683 upadacitinib, 3732 adalimumab, 132 baricitinib, 1770 tofacitinib). Compared with upadacitinib, patients initiating adalimumab [aOR (95% CI): 0.82 (0.69, 0.96)], baricitinib [0.46 (0.31, 0.68)], and tofacitinib [0.74 (0.62, 0.88)] were significantly less likely to achieve PDC≥80%. Risk of treatment discontinuation was significantly higher in patients treated with adalimumab [aHR (95% CI): 1.14 (1.01, 1.29)], baricitinib [1.48 (1.16, 1.90)], and tofacitinib [1.22 (1.07, 1.38)] compared with upadacitinib. Mean time to discontinuation was 256 (upadacitinib), 249 (adalimumab), 221 (baricitinib), and 239 (tofacitinib) days. Similar results were observed in patients with prior TNFi use. Patients with RA, regardless of recent TNFi experience, initiating upadacitinib were significantly more likely to be adherent and less likely to discontinue therapy compared to adalimumab, baricitinib, and tofacitinib in the first 12months of treatment.

Choice of and response to treatment in patients with early-diagnosed rheumatoid arthritis: Real-world data from an inception cohort in Japan (NICER-J)

ObjectiveVarious guidelines recommend that patients with early rheumatoid arthritis (RA) try to achieve clinical remission within 6 months, and early therapeutic intervention is important to this end. This study aimed to investigate short-term treatment outcomes of patients with early-diagnosed RA in clinical practice and to examine predictive factors for achieving remission. MethodsOf the 210 patients enrolled in the multicenter RA inception cohort, 172 patients who were followed up to 6 months after treatment initiation (baseline) were included. Logistic regression analysis was used to examine the impact of baseline characteristics on achievement of Boolean remission at 6 months. ResultsParticipants (mean age, 62 years) initiated treatment after a mean of 19 days from RA diagnosis. At baseline and 3 and 6 months after treatment initiation, proportions of patients using methotrexate (MTX) were 87.8%, 89.0%, and 88.3%, respectively, and rates of Boolean remission were 1.8%, 27.8%, and 34.5%, respectively. Multivariate analysis revealed that physician global assessment (PhGA) (Odds ratio (OR): 0.84, 95% confidence interval (CI): 0.71–0.99) and glucocorticoid use (OR: 0.26, 95% CI: 0.10–0.65) at baseline were independent factors that predicted Boolean remission at 6 months. ConclusionAfter a diagnosis of RA, satisfactory therapeutic effects were achieved at 6 months after the initiation of treatment centered on MTX according to the treat to target strategy. PhGA and glucocorticoid use at treatment initiation are useful for predicting the achievement of treatment goals.

Epimedii Herba: An ancient Chinese herbal medicine in the prevention and treatment of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic, progressive inflammatory and systemic autoimmune disease resulting in severe joint destruction, lifelong suffering and considerable disability. Diverse prescriptions of traditional Chinese medicine (TCM) containing Epimedii Herba (EH) achieve greatly curative effects against RA. The present review aims to systemically summarize the therapeutic effect, pharmacological mechanism, bioavailability and safety assessment of EH to provide a novel insight for subsequent studies. The search terms included were "Epimedii Herba", "yinyanghuo", "arthritis, rheumatoid" and "Rheumatoid Arthritis", and relevant literatures were collected on the database such as Google Scholar, Pubmed, Web of Science and CNKI. In this review, 15 compounds from EH for the treatment of RA were summarized from the aspects of anti-inflammatory, immunoregulatory, cartilage and bone protective, antiangiogenic and antioxidant activities. Although EH has been frequently used to treat RA in clinical practice, studies on mechanisms of these activities are still scarce. Various compounds of EH have the multifunctional traits in the treatment of RA, so EH may be a great complementary medicine option and it is necessary to pay more attention to further research and development.

Consistency of recommendations for pharmacotherapy of rheumatoid arthritis.

Background: Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory arthropathy. Recommendations for RA, specifically on pharmacotherapy, are essential in clinical practice. However, the direction and strength of recommendations are controversial across current clinical practice guidelines (CPGs) of RA. Objective: To systematically analyze the consistency of recommendations regarding pharmacotherapy of RA across CPGs. Methods: 11 electronic databases and websites were comprehensively searched from inception to 14 March 2022, to identify CPGs for diagnosis, therapy, and management of RA. Unambiguous and discrete specifications of the population-intervention-comparison (PIC) framework were used to classify the recommendations. Based on the PIC framework, consistency analyses across CPGs on pharmacotherapy of RA were performed. Two researchers reached a consensus on coding the direction and strength of each recommendation. Results: Finally, 26 CPGs were included in this study, and 14 of them, which included pharmacotherapy, were performed consistency analysis. 1) 64 recommendations from 14 CPGs were classified into 18 PICs. 2) Seven PICs (38%) were consistent in direction and strength, 10 PICs (56%) were consistent in direction but inconsistent in strength, and one PIC (6%) was inconsistent in direction (hydroxychloroquine, HCQ). 3) Sensitivity analysis tested the robustness, and the inconsistency remained high. Conclusion: The direction was highly consistent among the recommendations of pharmacotherapy for RA, but the strength was highly inconsistent. Reasons for the inconsistency need to be further investigated, and consistent recommendations could guide the pharmacotherapy of RA in clinical practice.

Anti-cyclic citrullinated peptide antibody (ACPA) and Rheumatoid arthritis: Clinical relevance

Rheumatoid Arthritis (RA) is the most common auto-immune, chronic inflammatory joint disease. Predominantly a musculoskeletal condition with a wide spectrum of skeletal and extra-skeletal manifestations, RA has a significant footfall in orthopaedic clinical practice worldwide.RA is essentially a clinical diagnosis; however, laboratory and radiographic investigations can provide complementary diagnostic and prognostic information about the disease. Early diagnosis and initiation of appropriate management are crucial since RA patients can develop chronic, erosive arthritis if left untreated or if treatment is delayed.Rheumatoid Factor (RF) antibody test is routinely employed for diagnostic purposes in patients with suspected RA. However, RF is present only in 70%–80% of patients with RA and can be non-specific. Therefore, Anti-cyclic citrullinated peptide antibody (ACPA), a novel immunological marker for RA is increasingly being utilised to provide higher specificity and a better prognostic indicator in RA patients.We describe the immunological basis of ACPA test and highlight its current applications in the diagnosis, prognosis and monitoring of RA in clinical practice.

The Potential Effects of Dielectric Barrier Discharge Plasma on the Extraction Efficiency of Bioactive Compounds in Radix Paeoniae Alba.

Radix paeoniae alba (RPA) is a kind of herbal medicine of traditional Chinese medicine (TCM) that is widely used for the treatment of liver diseases and rheumatoid arthritis in clinical practice. As a result of the low extraction efficiency of RPA by the conventional method, many patients are given high dosages. In this study, four exposure doses of dielectric barrier discharge (DBD) plasma (0, 60, 120, and 180 s) were applied to modify the extraction efficiency of paeoniflorin, benzoylpaeoniflorin, tannic acid, gallic acid, 2′-hydroxy-4′-methoxyacetophenone, and polysaccharide in RPA. Finally, the application of plasma for 180 s exhibited a 24.6% and 12.0% (p < 0.001) increase of tannic acid and polysaccharide contents, however, a 2.1% (p < 0.05) and 5.4% (p < 0.001) reduction of paeoniflorin and gallic acid composition, respectively, and no significant difference (p > 0.05) in results obtained from benzoylpaeoniflorin and 2′-hydroxy-4′-methoxyacetophenone contents. Our results of scanning electron microscopy (SEM), automatic specific surface area and pore analyzer, Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), and thermal gravimetric analysis (TGA) indicated that DBD plasma can etch the surface and undergo graft polymerization by reactive species thereby changing the water/oil holding capacity and eventually changing the extraction efficiency of bioactive compounds in RPA. Overall, our observations provide a scientific foundation for modifying the extraction efficiency of bioactive ingredients related to the pharmacological activities of RPA.

Short- and longer-term cancer risks with biologic and targeted synthetic disease-modifying antirheumatic drugs as used against rheumatoid arthritis in clinical practice.

ObjectiveTo estimate the occurrence and relative risks of first-ever-incident non-cutaneous cancer overall and for 16 sites in patients with RA treated with biologic and targeted synthetic DMARDs (b/tsDMARDs), by time since treatment start, attained age, and duration of active treatment.MethodsThis is an observational nationwide and population-based cohort study of patients with RA (n = 69 308), treated with TNF inhibitors (TNFi; adalimumab, certolizumab, etanercept, golimumab, infliximab) or other b/tsDMARDs (abatacept, rituximab, baricitinib, tofacitinib and tocilizumab) compared with RA patients not treated with b/tsDMARDs, and matched general population referents (n = 109 532), 2001–2018. The study was based on prospectively collected data from the Swedish Rheumatology Quality Register and from other registers, linked to the national Swedish Cancer Register. Incidence rates and hazard ratios were estimated via Cox regression adjusted for co-morbidities and other health characteristics.ResultsBased on 8633 incident cancers among RA patients, the overall relative risk of cancer with TNFi [hazard ratio (HR) = 1.0] was neither increased nor did it change with time since treatment start, duration of active treatment, or attained age, when compared with b/tsDMARD-naïve RA. For other b/tsDMARDs, we noted no consistent signal of increased overall risks (HRs ranged from 1.0 to 1.2), but there were statistically significant estimates above 1 for abatacept with 2–5 years of active treatment, for older age groups, and between several of the bDMARDs and urinary tract cancer.ConclusionTNFis, as used long term in clinical practice against RA, are not linked to increased risks for cancer overall. For other b/tsDMARDs, and for site-specific risks, our results are generally reassuring but contain signals that call for replication.

POS0221 COMPARISON OF TOFACITINIB AND BARICITINIB BY INVERSE PROBABILITY OF TREATMENT WEIGHTING ANALYSES BASED ON PROPENSITY SCORE IN PATIENTS WITH RHEUMATOID ARTHRITIS IN REAL CLINICAL PRACTICE

Background:Tofacitinib (TOFA) and baricitinib (BARI) have been widely used in many regions for treatment of rheumatoid arthritis (RA). The selection of JAK inhibitor for RA treatment based on patient type remains a major concern.Objectives:The differences of efficacy between each Janus kinase (JAK) inhibitors have not been clarified in the patients with RA in clinical practice. Here, we compared the efficacy between TOFA and BARI in clinical practice.Methods:A retrospective observational study. The efficacy of TOFA (n=156) in patients with RA was compared with BARI (n=138). Selection bias was reduced to a minimum using propensity score-based inverse probability of treatment weighting (IPTW). We analyzed the trajectories of changes in disease activity in patients receiving TOFA or BARI using growth mixture modeling (GMM). Multivariable logistic regression analysis was performed to identify factors contributing to belonging to treatment-resistance group defined by GMM. The observation period of the study was 24 weeks.Results:No significant difference was observed in patient characteristics between the TOFA and BARI groups in after adjustment by propensity score-based IPTW. The retention rates over 24 weeks did not differ between the TOFA and BARI groups. No difference was observed in the incidence of adverse events in the TOFA and BARI groups. Clinical disease activity index (CDAI) at week 24 after the introduction of JAK inhibitors was 8.0 ± 8.9 and 6.2 ± 7.2 in the TOFA and BARI group, respectively. The rates of CDAI-remission at week 24 in the TOFA and BARI groups were 43/153 (28.3%) and 57/141 (40.4%), respectively. Compared to the TOFA group, the BARI group showed a significantly lower CDAI (⊿CDAI=-1.9, 95% confidence interval: -3.7 to -0.3, p=0.02) and a significantly higher rate of CDAI-remission (odds ratio: 1.7, 95% CI: 1.1–2.7, p=0.04) at week 24. Similarly, at week 24, SDAI was significantly lower in the BARI group (TOFA vs. BARI = 10.1 ± 9.9 vs. 7.3 ± 7.5, ⊿SDAI=-2.2, 95% CI: -4.2 to -0.2, p=0.04), and the rates of SDAI-remission (OR: 1.6, 95% CI: 1.0–2.6, p=0.04).The patients were divided into two groups: patients with MDA to HDA at baseline (Group 1) and patients with HDA at baseline than Group 1 (Groups 2 and 3) based on the analysis of the trajectories of CDAI using GMM, In Groups 1 and 2, disease activity was improved immediately after the introduction of JAK inhibitors. In Group 3, disease activity was partially improved, and LDA was not achieved at week 24 after the introduction of JAK inhibitors. The patients in Group 3 were resistant to treatment (Group 3: treatment-resistance group).When multivariable logistic regression analysis was performed for all patients receiving JAK inhibitors, the factors contributing to belonging to treatment-resistance group were: high baseline HAQ-DI score (OR: 1.76, 95% CI: 1.09–2.84, p=0.02) and high number of biological disease-modifying anti-rheumatic drugs (bDMARDs) used before JAK inhibitors (OR: 1.51, 95% CI: 1.16–1.95, p=0.002) and TOFA use (OR: 2.13, 95% CI: 1.05–4.30, p=0.03).Next, multivariable logistic regression analysis was separately performed for each treatment group. The patients receiving more bDMARDs before the JAK inhibitor were more likely to belong to treatment-resistance group in the TOFA group (OR: 1.76, 95% CI: 1.24–4.06). Among patients with RA who received TOFA, those who had received ≥4 bDMARDs before the introduction of TOFA were more likely to be classified into the treatment-resistant group.In the BARI group, multivariable logistic regression analysis did not identify any factors associated with belonging to treatment-resistance group.Conclusion:TOFA may be partially effective in patients resistant to many bDMARDs. Consequently, efficacy may differ between TOFA and BARI. Because TOFA was less effective in RA patients resistant to ≥4 bDMARDs, the present study suggests that BARI may be more appropriate for RA patients resistant to many bDMARDs.Disclosure of Interests:Yusuke Miyazaki Speakers bureau: Eli Lilly, Shingo Nakayamada Speakers bureau: Bristol-Myers, UCB, Astellas, Abbvie, Eisai, Pfizer, Takeda, Kazuhisa Nakano Speakers bureau: Bristol-Myers, Sanofi, AbbVie, Eisai, Eli Lilly, Chugai, Pfizer, Takeda, and Mitsubishi-Tanabe, Satoshi Kubo Speakers bureau: Bristol-Myers, Yoshino Inoue: None declared, Yoshihisa Fujino: None declared, Yoshiya Tanaka Speakers bureau: Abbvie, Daiichi-Sankyo, Chugai, Takeda, Mitsubishi-Tanabe, Bristol-Myers, Astellas, Eisai, Janssen, Pfizer, Asahi-kasei, Eli Lilly, GlaxoSmithKline, UCB, Teijin, MSD, and Santen

Characteristics of patients with difficult-to-treat rheumatoid arthritis in clinical practice.

The aim of this study was to investigate the clinical characteristics of patients with difficult-to-treat RA (D2T RA) and the usefulness of switching to drugs with different modes of action in real-world. We reviewed all consecutive patients with RA treated at Keio University Hospital between 2016 and 2017 with a definition of D2T RA. We analysed clinical characteristics and evaluated the usefulness of changing drugs according to mode of action. Among 1709 patients with RA, 173 (10.1%) were D2T RA. The reason for the D2T RA was multi-drug resistance in 59 patients (34.1%), comorbidity in 17 (9.8%), and socio-economic reasons in 97 (56.1%). The multi-drug-resistance group had significantly higher tender joint count and evaluator global assessment than the other groups, despite receiving the most intensive treatment. The comorbidity group showed a significantly older age and higher rheumatic disease comorbidity index. Although changing the drug to another with a different mode of action was useful, the proportion of patients who achieved remission or low disease activity decreased as the number of switches increased. Of the patients with RA, 10.1% were still difficult to treat in clinical practice, despite intensive treatment. Their characteristics were distinct by the reasons of D2T RA, which suggests the need for a personalized approach to D2T RA.

Identification of circulating miR-22-3p and let-7a-5p as novel diagnostic biomarkers for rheumatoid arthritis.

Early and correct diagnosis would be beneficial for outcomes of rheumatoid arthritis (RA), but there are some limitations in current diagnostic tools. In this study, we aimed to evaluate the diagnostic value of circulating miR-22-3p and let-7a-5p in RA. Seventy-six RA patients, 30 systemic lupus erythematosus patients, 32 Sjögren's syndrome patients and 36 healthy donors recruited at the First Affiliated Hospital of Fujian Medical University (China) were included in this study. Circulating miR-22-3p and let-7a-5p in plasma were measured using reverse transcriptase quantitative PCR and serum cytokines were detected by cytometric bead array. The participants' clinical materials were also collected. Receiver operating characteristic curve analysis and correlation analysis were performed to assess the potential value of circulating miRNAs in RA. Circulating miR-22-3p and let-7a-5p are significantly increased in RA patients and able to distinguish RA patients from other populations. Circulating let-7a-5p has been shown to improve the diagnostic ability of current laboratory indicators anti-cyclic citrullinated peptide antibodies and rheumatoid factor. Moreover, the discriminatory capacity of both circulating miRNAs contribute to complement the diagnosis for seronegative RA. Meanwhile, correlation analysis reveals that circulating miR-22-3p positively correlates with haemoglobin, serum bilirubin, albumin and IL-17 but negatively correlates with mean platelet volume as well as let-7a-5p. The increased circulating miR-22-3p and let-7a-5p levels in RA patients, especially in seronegative RA patients, may provide potential promising diagnostic biomarkers for RA in clinical practice.

Effect of downregulation of serum MMP-3 levels by traditional Chinese medicine ingredients combined with methotrexate on the progression of bone injury in patients with rheumatoid arthritis: A protocol for a systematic review and meta-analysis.

Background:A large number of clinical studies have confirmed that after treatment with traditional Chinese medicine components such as sinomenine (SIN), the matrix -metalloproteinase3 (MMP-3) level of patients with rheumatoid arthritis (RA) shows a significant decrease, whereas MMP-3 can be involved in degrading bone matrix in humans, so in the progression of bone and joint injury in patients with RA, serum MMP-3 can be used as an important biochemical marker. The traditional Chinese medicine components commonly used in clinical practice include total glucosides of paeony (TGP), SIN, and tripterygium glycosides, which have the characteristics of disease-modifyinganti-rheumatic drugs and non-steroidal anti-inflammatory drugs, while they can reduce the toxic side effects of methotrexate (MTX), and their combination with other drugs such as MTX and leflunomide (HWA486) has become an important regimen for the treatment of RA in clinical practice. Therefore, we designed this study protocol to evaluate the adjuvant effect of commonly used traditional Chinese medicine components combined with MTX in the treatment of osteoarticular injury in RA.Methods:The search time was set from January 2000 to September 2020 in this study. EMBASE database, Cochrane Library, PubMed, Web of Science, Science Direct, Chinese National Knowledge Infrastructure, China Biology Medicine disc (CBM), Chinese Scientifific Journals Database (VIP), and Wanfang Database were used as search sources to select the traditional Chinese medicine components that reduce MMP-3 and use MTX in the treatment of RA. Clinical randomized controlled trials were used, and inclusion criteria and exclusion criteria were set for screening. In this study, MMP-3, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), cyclic peptide containing citrulline (CCP) and rheumatoid factor (RF) were used as the main outcomes, and the improvement of Disease Activity Score 28 (DAS28), joint bone mineral density, Clinical Disease Activity Index (CDAI), and other clinically relevant symptoms was selected as the secondary outcomes. Revman software version 5.3 was used for statistical analysis of data and risk assessment of deviation in this meta-analysis. In this study, one researcher performed study direction selection, literature inquiry, and literature download, and 2 independent reviewers performed literature data extraction and literature quality assessment. Dichotomized data are expressed as relative risk, continuous data are expressed as mean difference or standard mean difference, and finally fixed-effect model or random-effect model is used for synthesis according to the heterogeneity of data.Results:To evaluate the effect of downregulation of MMP-3 level by traditional Chinese medicine components combined with MTX on the progression of bone injury in patients with RA by serum MMP-3, ESR, CRP, CCP, and RF.Conclusion:This study protocol can be used to evaluate the efficacy and safety of traditional Chinese medicine components combined with MTX in the treatment of bone injury in patients with RA.Ethics and dissemination:This study is a secondary study based on the published clinical research; therefore, approval from an ethics committee is not required for this study. In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocol (PRISMA-P), the results of this study will be published in peer-reviewed scientific journals and conference papers.Registration number:is INPLASY202090064.

Can the adherence to quality of care indicators for early rheumatoid arthritis in clinical practice reduce risk of hospitalisation? Retrospective cohort study based on the Record Linkage of Rheumatic Disease study of the Italian Society for Rheumatology

ObjectiveTo describe the adherence to quality of care indicators in early rheumatoid arthritis (RA) and to evaluate its impact on the risk of hospitalisation in a real-world setting.DesignRetrospective cohort study.SettingPatients...

Prescribing patterns and clinical outcomes of biological disease-modifying anti-rheumatic drugs for rheumatoid arthritis in Spain.

New treatments in rheumatoid arthritis (RA) have been developed to improve patient outcomes, raise their quality of life, and reduce joint damage, but long-term responses and remission remain low. This study aimed to analyse the Spanish prescribing patterns and the effectiveness of biological (b) disease-modifying anti-rheumatic drugs (DMARDs) available for RA in clinical practice. An observational retrospective study was performed in a teaching hospital, analysing the different combinations of drugs prescribed, real-life effectiveness and reasons for withdrawal. In total, 210 patients were included, with 19 different patterns (pharmacological groups alone or in combination) of treatment prescribed. Most patients started their treatment with a conventional synthetic (cs) DMARD alone or in combination with a glucocorticosteroid. Among the initial patterns, treatment with only one csDMARD showed a longer duration. The time to first bDMARD was 6 years. TNF-α inhibitors are the most commonly prescribed drugs as initial biological treatments. The highest percentages of good responses and remissions were achieved with tocilizumab, etanercept and infliximab. The time to remission was also lower with tocilizumab. Lack of response, adverse effects and remission were the main causes of bDMARD withdrawal. The duration of treatments until withdrawal was similar among bDMARDs, except for rituximab, for which the duration was slightly shorter. Prescribing pattern analysis showed the highest responses and remission rates with tocilizumab and TNF-α inhibitors. The main reasons for withdrawal were lack of response and adverse effects. Further research is needed to improve pharmacological RA management in real-life settings.

Factors associated with long-term persistence of rituximab in rheumatoid arthritis in clinical practice: RITAR Study

Background and objectiveTreatment of rheumatoid arthritis with rituximab (RTX) requires repeated cycles, but there is no well-established retreatment regimen in dose and frequency. The objective was to analyse the persistence of RTX treatment and factors that influence in terms of routine clinical practice. MethodsRituximab in rheumatoid arthritis (RITAR Study) is an observational, retrospective study that analyses the persistence of RTX in a cohort from 2003 to 2015. Persistence was calculated by the Kaplan–Meier analysis; curves were compared with the Log-Rank test. Cox regression was used to quantify the risk of discontinuation and multivariate analyses were conducted to determine the factors associated with the persistence of the treatment. Results454 cycles of RTX in 114 patients were included. Median survival was 10.0 years and incidence rate of discontinuation was 7.7 per 100patients/year. Factors associated with persistence were autoantibody positivity and use of RTX in combination with csDMARDs. Sex, age, number of comorbidities, rheumatoid arthritis evolution, number of complications, basal DAS28, basal HAQ, number of lines of treatment, fixed or on demand retreatment and year of RTX starting were not associated. Multivariable models confirmed the relationship between autoantibody positivity, monotherapy and persistence of RTX. ConclusionsThe persistence of RTX in clinical practice is higher in seropositive patients and in those who are treated with RTX associated with a csDMARD. Dose per cycle and retreatment frequency do not have a decisive role in rituximab persistence.

THU0108 REAL-WORLD RADIOGRAPHIC PROGRESSION IN RA WITH BIOLOGIC DMARDS

Background:As structural damage is irreversible and strongly associated with functional disability1, it is an important outcome to be prevented in rheumatoid arthritis (RA). Acute phase markers, rheumatoid factor (RF) and anti-citrullinated protein (anti-CCP) positivity are important predictors of erosive disease2. Previous studies conducted in real life setting have divergent results regarding the role of disease activity in radiographic progression3,4.Objectives:To evaluate the impact of disease activity and biologic disease modifying anti-rheumatic drugs (bDMARDs) on radiographic progression of established RA in clinical practice in southern Brazilian public health system.Methods:Longitudinal retrospective study including patients with RA (1987 ACR criteria) treated with bDMARDs and followed from 2015 to 2019. Clinical and demographic data were collected at baseline. Radiographs of hands and feet were performed yearly. X-rays were scored according to the van der Heijde-modified total Sharp method (vdH-mTSS) in known chronological order. Clinical relevant radiographic progression (CRRP) was defined as an increase ≥3 units on the score per year5.Demographic, clinical, and radiographic characteristics of RA patients with or without relevant progression were compared with Fisher exact and Mann-Whitney test.Results:Seventy-five patients were included. The patients’ characteristics are shown in table 1. Twenty three (30%) patients presented CRRP at any time point of the follow up (figure 1). Mean DAS28-ESR at baseline was higher in patients who progressed radiographically, than those who did not progress (4.8±1.1 vs 3.5±1.1; p &lt; 0.001). No patient in remission at baseline presented with CRRP. Radiographic progression occurred in 15% of patients in low disease activity, 34% of patients in moderate disease activity and 57% of patients in high disease activity at baseline, depicting a linear relation between categories of disease activity and CRRP. RF, anti-CCP, disease duration, educational level, smoking status, total vdH-mTSS at baseline, number and duration of biologic DMARDs were not associated with CRRP. No single biologic DMARD was associated with worse radiological prognosis.Table 1.Baseline characteristics and bDMARD treatment during 5 years of follow upCharacteristicsN = 75Age, yrs, mean ± SD58.1 ± 10.1Female, n (%)65 (86.6)Disease duration, yrs, mean ± SD16.2 ± 7.6IgM RF positivity, n (%)69 (92)Anti-CCP positivity, n (%)27 (75) *DAS28-ESR, mean ± SD4.2 ± 1.0Educational level, n(%) Elementary school (≤ 8years)49 (65) Intermediate school (9-12 years)23 (30,6) University/college degree3 (4)SmokingCurrent or former31 (41.3)Never44 (58,7)vdH-mTSS, median (IQR)21 (5-53)Number of bDMARD, mean ± SD2.4 ± 1.1Duration of bDMARD, yrs, mean ± SD7.4 ± 2.6Methotrexate use, n, %61 (81)Biologic DMARD184**TNF inhibitors, n, %106 (57.6)Tocilizumab, n, %30 (16.3)Abatacept, n, %25 (13.6)Rituximab, n, %23 (12.5)RF rheumatoid fator anti-CCP anti-citrullinated protein bDMARD biologic disease-modifying anti-rheumatic drug ESR erythrocyte sedimentation rate DAS28 disease activity in 28 joints vdH-mTSS van der Heijde-modified total Sharp score IQR interquartile range *information available from 36 patients **all bDMARD treatmentsConclusion:In contrast to controlled clinical trials, real-world studies have shown that patients with RA treated with bDMARD still develop radiological progression. We observed that despite prognostic factors, achievement of treatment target is the most important factor to prevent articular damage in RA.

Routine Assessment of Patient Index Data 3 (RAPID3) alone is insufficient to monitor disease activity in rheumatoid arthritis in clinical practice

ObjectiveTo test the longitudinal association between patient-reported outcome, Routine Assessment of Patient Index Data 3 (RAPID3) and the Disease Activity Score in 28 joints that includes the erythrocyte sedimentation rate...

Suppression of joint destruction with subcutaneous tocilizumab for Japanese patients with rheumatoid arthritis in clinical practice

Objectives: To investigate the efficacy of suppressing joint destruction with subcutaneous tocilizumab (TCZ-SC) for Japanese rheumatoid arthritis (RA) patients in the real-world clinical setting.Methods: This 1-year prospective, multicenter study included 110 RA patients in whom TCZ-SC was newly initiated. Primary endpoint was the change from baseline in vdH-modified total Sharp score (mTSS) at week 52. Structural remission was defined as yearly mTSS of 0.5 or less. Disease activity was evaluated using the disease activity score (DAS28-ESR) and clinical disease activity index (CDAI).Results: At baseline, the patients’ mean age was 58.6 years, and the mean disease duration was 10.6 years. The proportion of patients who were naïve for biologics was 44.5%, and 64.5% concomitantly received methotrexate. The yearly mTSS showed significant improvement from 9.41 before TCZ-SC initiation to −0.15 after 52 weeks. The structural remission rate was 76.1%. After 52 weeks, the DAS28-ESR and CDAI remission rates were 52% and 21%, respectively. Although the previous usage of biologics and baseline disease activity significantly affected the clinical remission, no factors with significant effects on structural remission were identified.Conclusion: These findings support the efficacy of TCZ-SC in suppressing disease activity as well as joint destruction over a 1-year period.