Search

This exploratory study aimed to examine the impact of abatacept treatment on bone structure in patients with rheumatoid arthritis (RA) using high-resolution peripheral quantitative computed tomography (HR-pQCT). RA patients initiating either abatacept or newly introduced csDMARDs were enrolled in this prospective, non-randomized, two-group study. Bone structure in the 2nd and 3rd metacarpal heads was assessed using HR-pQCT at 0, 6, and 12 months after enrollment. Synovitis was evaluated using musculoskeletal ultrasound and MRI. The adjusted mean between-group differences (abatacept–csDMARDs group) were estimated using a mixed-effect model. Thirty-five patients (abatacept group: n = 15; csDMARDs group: n = 20) were analyzed. Changes in erosion volume, depth and width were numerically smaller in the abatacept group compared to the csDMARDs group (adjusted mean between-group differences: − 1.86 mm3, − 0.02 mm, and − 0.09 mm, respectively). Over a 12-month period, 5 erosions emerged in the csDMARDs group, while only 1 erosion appeared in the abatacept group. Compared to csDMARDs, abatacept better preserved bone microarchitecture; several components of bone microarchitecture were significantly worsened at 6 months in the csDMARDs group, but were not deteriorated at 6 months in the abatacept group. Changes in synovitis scores were similar between the two treatment groups. Our results indicate that abatacept prevented the progression of bone erosion including new occurrence, and also prevented worsening of bone strength independently with synovitis compared to csDMARDs including MTX. Thus, abatacept treatment may provide benefits not only in inhibiting the progress of bone erosion but also in preventing bone microarchitectural deterioration. [ABSTRACT FROM AUTHOR]

Objectives This study contributes to the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)'s effort to define 'difficult-to-treat' PsA (D2T-PsA), leveraging insights of healthcare professionals who are GRAPPA members. The primary objective is to inform GRAPPA's D2T PsA project, ensuring the consensus definition reflects clinical experience and expertise. Methods An online survey was conducted among GRAPPA's healthcare professionals managing PsA patients. The survey covered demographic details, structured questions, and open-ended queries to gather comprehensive insights into the experts' viewpoints. Results About 223 physicians completed the survey, comprising 179 (80.2%) rheumatologists and 40 (17.9%) dermatologists. The majority, 184 (82.5%), favoured establishing distinct definitions for D2T-PsA and complex-to-manage PsA (C2M-PsA). Furthermore, 202 (90.5%) supported a definition that includes objective inflammation signs (clinical, laboratory, imaging, among others). However, opinions varied on the criteria for prior treatment failures, with most (93, 41.7%) favouring a definition that includes at least one conventional synthetic disease-modifying anti-rheumatic drug and two or more biological- or targeted-synthetic-DMARDs with different mechanisms of action. Conclusion The survey reveals a majority opinion among GRAPPA experts favouring the differentiation between D2T-PsA and C2M-PsA, and the inclusion of objective inflammatory markers in these definitions. However, there is less than 50% agreement on the specific treatment failure criteria, particularly regarding the number of therapies needed to classify PsA as D2T. These findings suggest a need for continued discussion to reach a more unified approach in defining D2T-PsA, reflecting the complexity of the condition. [ABSTRACT FROM AUTHOR]

Abstract This exploratory study aimed to examine the impact of abatacept treatment on bone structure in patients with rheumatoid arthritis (RA) using high-resolution peripheral quantitative computed tomography (HR-pQCT). RA patients initiating either abatacept or newly introduced csDMARDs were enrolled in this prospective, non-randomized, two-group study. Bone structure in the 2nd and 3rd metacarpal heads was assessed using HR-pQCT at 0, 6, and 12 months after enrollment. Synovitis was evaluated using musculoskeletal ultrasound and MRI. The adjusted mean between-group differences (abatacept–csDMARDs group) were estimated using a mixed-effect model. Thirty-five patients (abatacept group: n = 15; csDMARDs group: n = 20) were analyzed. Changes in erosion volume, depth and width were numerically smaller in the abatacept group compared to the csDMARDs group (adjusted mean between-group differences: − 1.86 mm3, − 0.02 mm, and − 0.09 mm, respectively). Over a 12-month period, 5 erosions emerged in the csDMARDs group, while only 1 erosion appeared in the abatacept group. Compared to csDMARDs, abatacept better preserved bone microarchitecture; several components of bone microarchitecture were significantly worsened at 6 months in the csDMARDs group, but were not deteriorated at 6 months in the abatacept group. Changes in synovitis scores were similar between the two treatment groups. Our results indicate that abatacept prevented the progression of bone erosion including new occurrence, and also prevented worsening of bone strength independently with synovitis compared to csDMARDs including MTX. Thus, abatacept treatment may provide benefits not only in inhibiting the progress of bone erosion but also in preventing bone microarchitectural deterioration.

The impact of the Coronavirus disease 2019 (COVID-19) pandemic on autoimmune diseases (AID) patients has been an important focus. This study was undertaken to characterize the incidence, clinical manifestations and hospitalization among AID affected by COVID-19 and to analyze the association between immunomodulatory medication and these outcomes. Clinical, demographic, maintenance treatment, symptoms and disease course data and outcomes of AID patients with COVID-19 infection were assessed via an online survey tool and printed copy from 1 January till February 28, 2023. A total of 432 patients with AID were enrolled in the study. The results showed the most common conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) was hydroxychloroquine (HCQ). The usage of csDMARDs didn't increase the risk of COVID-19 infection. Patients who warranted hospitalization were significantly older. ILD was associated with higher hospitalization rate. No csDMARDs other than calcineurin inhibitor (CNI) was associated with increased risk of hospitalization. HCQ intake was associated with cough. Compared with no glucocorticoids (GCs) group, high doses of GCs were accompanied with higher proportion of gastrointestinal symptoms and tachycardia, lower proportion of sore throat and ageusia. GCs didn't provoke the COVID‐19 infection in patients with AID, but chronic use of oral GCs was significantly more common in those requiring hospitalization, and higher dose of GCs were correlated with higher risk of hospitalization. 97 patients discontinued csDMARDs after infection, which resulted in an elevated risk of hospitalization. Meanwhile, withdrawal of csDMARDs was associated with higher odds of disease flare and lower proportion of remission than maintenance groups. Collectively, our analysis provides the evidence that maintenance treatment of csDMARDs may be more prudent for AID patients during COVID-19 pandemic.

Background: Technetium [99Tc] methylene diphosphonate injection (99Tc-MDP) is widely used for the treatment of rheumatoid arthritis (RA), but there is still insufficient evidence for its application. Through the utilization of meta-analysis and systematic reviews, this study aimed to evaluate the effectiveness and safety of 99 TC-MDP in combination with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) for RA. Methods: This study was registered on PROSPERO in advance (CRD42021220780). A systematic search was conducted in PubMed, Embase, the Cochrane Library, and multiple international public databases from their inception to April 2023 to identify clinical randomized controlled trials exploring the use of 99Tc-MDP combined with csDMARDs in the treatment of RA. Each outcome was subjected to meta-analysis, and the quality of evidence was assessed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The American College of Rheumatology's 50 %/70 % response criteria scores (ACR50/70) scores were utilized as the primary effectiveness outcomes, and risks were measured by assessing the rates of AEs. Moreover, secondary efficacy outcomes were evaluated, including the Disease Activity Score 28 (DAS28) and bone mineral density (BMD) as joint function indicators and the erythrocyte sedimentation rate (ESR) and interleukin-17 (IL-17) as inflammatory indicators. Results: In this meta-analysis, a total of 34 studies (2296 patients) were included out of 1149 retrieved studies. The summarized results showed that the treatment group treated with the combination of 99Tc-MDP and csDMARDs had significantly higher ACR50 (RR = 1.32, 95 % CI: 1.13–1.55, P = 0.0004) and ACR70 (RR = 1.40, 95 % CI: 1.07–1.82, P = 0.01) scores than the control group receiving csDMARDs alone. In addition, the overall incidence of AEs was lower with the combination of 99Tc-MDP and csDMARDs than with csDMARDs alone (RR = 0.75, 95 % CI: 0.60–0.93, P = 0.009), but the possibility of phlebitis was higher in the treatment group (RR = 4.15, 95 % CI: 1.04–16.50, P = 0.04). In addition, the combination of 99Tc-MDP and csDMARDs had advantages over csDMARDs alone in improving DAS28 (WMD = 1.56, 95 % CI: 0.86–2.25, P

Abstract Background This exploratory study compared the inhibition of bone erosion progression in rheumatoid arthritis (RA) patients treated with a conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) plus denosumab versus csDMARD therapy alone and investigated the effects of denosumab on bone micro-architecture and other bone-related parameters using high-resolution peripheral quantitative computed tomography (HR-pQCT). Methods In this open-label, randomized, parallel-group study, patients with RA undergoing treatment with a csDMARD were randomly assigned (1:1) to continue csDMARD therapy alone or to continue csDMARDs with denosumab (60-mg subcutaneous injection once every 6 months) for 12 months. The primary endpoint was the change from baseline in the depth of bone erosion, measured by HR-pQCT, in the second and third metacarpal heads at 6 months after starting treatment. Exploratory endpoints were also evaluated, and adverse events (AEs) were monitored for safety. Results In total, 46 patients were enrolled, and 43 were included in the full analysis set (csDMARDs plus denosumab, N = 21; csDMARD therapy alone, N = 22). Most patients were female (88.4%), and the mean age was 65.3 years. The adjusted mean (95% confidence interval) change from baseline in the depth of bone erosion, measured by HR-pQCT, in the 2–3 metacarpal heads at 6 months was − 0.57 mm (− 1.52, 0.39 mm) in the csDMARDs plus denosumab group vs − 0.22 mm (− 0.97, 0.53 mm) in the csDMARD therapy alone group (between-group difference: − 0.35 mm [− 1.00, 0.31]; P = 0.2716). Similar results were shown for the adjusted mean between-group difference in the width and volume of bone erosion of the 2–3 metacarpal heads. Significant improvements in bone micro-architecture parameters were shown. The incidence of AEs and serious AEs was similar between the csDMARDs plus denosumab and the csDMARD therapy alone groups (AEs: 52.2% vs 56.5%; serious AEs: 4.3% vs 8.7%). Conclusions Although the addition of denosumab to csDMARDs did not find statistically significant improvements in bone erosion after 6 months of treatment, numerical improvements in these parameters suggest that the addition of denosumab to csDMARDs may be effective in inhibiting the progression of bone erosion and improving bone micro-architecture. Trial registration University Hospital Medical Information Network Clinical Trials Registry, UMIN000030575. Japan Registry for Clinical Trials, jRCTs071180018

Background: Ear, nose and throat (ENT) manifestations are common in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), yet how to treat these manifestations remains controversial. Therefore, we systematically reviewed the literature on the efficacy of therapies on ENT manifestations in AAV. Methods: A systematic review was conducted in accordance with the PRISMA guidelines, searching Medline, Embase and Cochrane libraries, including clinical studies between January 2005 and January 2022, in adults with AAV and ENT involvement, reporting on the effects of local and systemic therapy. The critical appraisal was performed using tools provided by the Cochrane Library and the level of evidence (LoE) was scored according to the Oxford Centre for Evidence-based Medicine. Results: After screening 5609 identified studies, 136 full-text articles were assessed. Finally, 31 articles were included for critical appraisal and data-extraction. Nearly all studies (n = 29) were retrospective and scored low on LoE. The included studies evaluated local interventions (n = 11), glucocorticoids combined with conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) (n = 8), rituximab (n = 6), or mepolizumab (n = 6). Due to heterogeneity across studies meta-analysis was not performed. Four studies on mepolizumab for sinonasal symptoms (n = 92) showed response in 33–100% and relapse in 35%. Local therapy for subglottic stenosis was effective in 80–100% of patients in 11 studies (n = 157), but relapses were common (up to 83%). In five studies, hearing improvement was observed in 56–100%, with better outcomes when glucocorticoids were combined with csDMARDs compared to glucocorticoids only. Conclusion: Response rates of ENT manifestations varied widely in studies and relapses were observed frequently. Heterogeneity among studies impaired comparison. [ABSTRACT FROM AUTHOR]

Objective We aim to provide real-world evidence on the effectiveness of patient-individual tapering of DMARDs for patients with RA in daily clinical practice using medical records and claims data. Methods We utilize data obtained through a controlled prospective cohort study in Germany conducted from July 2018 to March 2021. Participants consist of RA patients in sustained remission (>6 months) who were eligible for tapering at enrolment. Patients treated with individual tapering based on shared decision making (n  = 200) are compared with patients without any dose reduction (n  = 237). The risk of loss of remission and the risk of flare is assessed with risk-adjusted Kaplan–Meier estimators and Cox regressions. We evaluate differences in costs 1 year before and after baseline based on claims data for the subgroup of patients insured at one major sickness fund in Germany (n  = 76). Results The risk of flare (hazard ratio 0.88, 95% CI 0.59, 1.30) or loss of remission (hazard ratio 1.04, 95% CI 0.73, 1.49) was not statistically different between the individual tapering group and the continuation group. Minor increases of disease activity and decreases of quality of life were observed 12 months after baseline, again with no statistically significant difference. Drug costs decreased by 1017€ in the individual tapering group while they increased by 1151€ in the continuation group (P  < 0.01). Conclusion Individual tapering of DMARDs does not increase the average risk of experiencing flares or loss of remission. Encouraging rheumatologists and patients to apply tapering in shared decision making may be a feasible approach to allow individualization of treatment in RA. [ABSTRACT FROM AUTHOR]

There is increased cardiovascular (CV) morbidity and mortality in rheumatoid arthritis (RA) and other rheumatic and musculoskeletal diseases (RMDs). Systemic inflammation is highly involved in atherogenesis. Non-steroidal anti-inflammatory drugs (NSAIDs), primarily COX-2 inhibitors might increase CV risk. Corticosteroids might act as a double-edged sword as they exert both beneficial and negative effects on the CV system. NSAIDs and corticosteroids are anti-inflammatory, but, on the other hand, they might be potentially atherogenic. Conventional synthetic DMARDs (csDMARDs), such as antimalarials, methotrexate, sulfasalazine, leflunomide and cyclosporine A have good CV safety, however, leflunomide and cyclosporine A might cause hypertension. Biologic DMARDs, by suppressing inflammation and disease activity, might either reduce CV risk or at least not cause any harm in that respect. Recently, tofacitinib and most likely other Janus kinase inhibitors have been associated with increased CV risk, at least in RMD patients with high CV risk at baseline. In clinical practice, EULAR and other recommendations guide the rheumatologist when screening for and managing CV comorbidities. [ABSTRACT FROM AUTHOR]

Objectives Sex is well known to influence risk, severity and treatment outcomes of RA, although the underlying causes are uncertain. The aim of this research was to examine whether factors influencing female sex hormones (reproductive status and exogenous sex hormone use) are associated with the efficacy of DMARDs. Methods Individual participant data were pooled from five phase 3 clinical trials where RA patients were treated with tocilizumab and/or conventional synthetic DMARDs. The primary outcome was the time to first remission according to the Simplified Disease Activity Index. The relationship between menopausal status or use of exogenous sex hormones and the time of first remission was assessed via Cox proportional analysis. Analysed data included sex, baseline menopausal status (premenopausal, perimenopausal, early postmenopausal and postmenopausal), participant age, body mass index, race, number of previous DMARDs and baseline disease activity. Results Analysis included 4474 female patients, of whom 2817 (62.9%) were postmenopausal, 202 (4.5%) were early postmenopausal, 1021 (22.8%) were premenopausal and 414 (9.2%) were perimenopausal. Of these, 221 (7.8%), 13 (6.4%), 255 (25%) and 47 (11.4%), respectively, were taking exogenous sex hormones. In the pooled analysis, perimenopausal status was associated with reduced remission compared with premenopausal status [adjusted HR 0.78 (95% CI 0.61, 0.99)]. Sex hormone use was associated with significantly higher remission [adjusted HR 1.20 (95% CI 1.01, 1.43)]. Conclusion Perimenopausal women were less likely to achieve remission compared with premenopausal RA patients. The use of exogenous sex hormones appeared to be associated with more frequent remission in female RA patients, particularly those who were perimenopausal and early postmenopausal, although further research is required to confirm and identify the drivers for this observation and how it interacts with menopausal status. [ABSTRACT FROM AUTHOR]

Introduction: Early psoriatic arthritis (PsA) diagnosis is critical to prescribe timely treatment to prevent the irreversible joint damage and the many other problems that patients with PsA experience. This retrospective study aimed to highlight the benefits of a Rheuma–Derma Clinic focused on the early diagnosis and prompt treatment of PsA with a shared approach among Italian psoriasis patients. Diagnosing PsA early is the main goal to reduce joint damage and disability in the patients affected. Studies describing the results of rheuma–derma clinics aimed to reach this goal emerged in the last decade. This study presents limitations and advantages typical of retrospective designs. Methods: A Rheuma–Derma Clinic was created in 2017 at the Rheumatology Department of the Hospital Policlinico Gaspare Rodolico of the University of Catania in San Marco, Italy. This study compared the number of patients under disease-modifying antirheumatic treatment 5 years before and after the joint clinic was created. A rheumatologist and dermatologist simultaneously assessed patients with psoriasis and/or PsA to obtain a rapid multidisciplinary diagnostic approach and a shared therapeutic strategy. In addition, demographic, clinical, and clinimetrics data were collected. Results: The number of patients with PsA receiving biological disease-modifying antirheumatic drugs increased 47% (from 255 to 374 patients) before and after the joint clinic was implemented. Likewise, those receiving conventional synthetic disease-modifying antirheumatic drugs increased by 47% (from 367 to 539) as well. Additionally, for all the clinimetrics evaluated (DAS28, HAQ, BASDAI, DAPSA, PASI, PGA), there was an improvement over the 12 months under the Rheuma–Derma Clinic care. The measures that improved the most were DAPSA, PGA, PASI, and BASDAI. Conclusion: The implementation of the Rheuma–Derma Clinic was associated with an increase in the number of patients diagnosed, the number of patients with PsA receiving DMARD treatments, and improvements in clinimetrics among the study participants. Plain language summary: Psoriatic arthritis needs to be detected early to treat it correctly and for its consequences in patients with psoriasis to be prevented. This study was carried out to find out if shared clinics where rheumatologists and dermatologists care for patients together helped to control psoriatic arthritis better and improve the life of the patients affected by it. The shared clinic was created in 2017 at the Rheumatology Department of the Hospital Policlinico Gaspare Rodolico of the University of Catania in San Marco, Italy. The study collected information about the number of patients diagnosed with psoriasis and psoriatic arthritis, the number of patients receiving treatments, and the results of quality of life and other standard tests. During the time that the joint clinic was in place, the number of patients receiving treatments specific for diseases such as psoriatic arthritis increased from 622 (before the clinic was started) to 913. The patients treated in this clinic also had improvements in their quality of life and other aspects. This study found that a clinic where rheumatologists and dermatologists work together to care for patients can increase the number of patients treated with drugs that are specific for their disease and improve their overall health. [ABSTRACT FROM AUTHOR]

Introduction: In patients with rheumatoid arthritis (RA), attaining remission or low disease activity (LDA), as recommended by the treat-to-target approach, has shown to yield improvement in symptoms and quality of life. However, limited evidence from real-world settings is available to support the premise that better disease control is associated with lower healthcare costs. This study fills in evidence gaps regarding the cost of care by RA disease activity (DA) states and by therapy. Methods: This retrospective cohort study linked medical and prescription claims from Optum Clinformatics Data Mart to electronic health record data from Illumination Health over 1/1/2010–3/31/2020. Mean annual costs for payers and patients were examined, stratifying on DA state and baseline use of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), biologics, and targeted synthetic (ts)DMARDs. Subgroup analysis examining within-person change in costs pre- and post-initiation of new therapy was also performed. Descriptive statistics, means, and boot-strapped confidence intervals were analyzed by DA state and by RA therapy. Furthermore, multivariate negative binomial regression analysis adjusting for key baseline characteristics was conducted. Results: Of 2339 eligible patients, 19% were in remission, 40% in LDA, 29% in moderate DA (MDA), and 12% in high DA (HDA) at baseline. Mean annual costs during follow-up were substantially less for patients in remission ($40,072) versus those in MDA ($56,536) and HDA ($59,217). For patients in remission, csDMARD use was associated with the lowest mean annual cost ($25,575), tsDMARD was highest ($75,512), and tumor necrosis factor inhibitor (TNFi) ($69,846) and non-TNFi ($57,507) were intermediate. Among new TNFi (n = 137) and non-TNFi initiators (n = 107), 31% and 26% attained LDA/remission, respectively, and the time to achieve remission/LDA was numerically shorter in TNFi vs. non-TNFi initiators. For those on biologics, mean annual within-person medical and inpatient costs were lower after achieving LDA/remission, although pharmacy costs were higher. Conclusions: Cost of care increased with increasing DA state, with patients in remission having the lowest costs. Optimizing DA has the potential for substantial savings in healthcare costs, although may be partially offset by the high cost of targeted RA therapies. [ABSTRACT FROM AUTHOR]

Background: Muscle wasting, also known as myopenia, is frequent in rheumatoid arthritis (RA). To date, it is still unknown if the failure of pharmacologic therapies increases the risk of myopenia in RA. Objective: To identify if treatment failure with conventional synthetic DMARDs (csDMARDs) constitutes an independent risk factor of muscle wasting in women with RA. Methods: This was a cross-sectional study. We included 277 women with RA. Assessments in RA patients included: clinical, epidemiological, and therapeutic variables. The skeletal muscle index (SMI) was estimated by DXA, and myopenia was diagnosed if they had an SMI < 5.45 kg/m2. Multivariable logistic regression models identified risk factors of myopenia. Results: Muscle wasting was observed in 28.2% of patients with RA. The risk factors of myopenia in RA were menopausal (OR: 4.45, 95% CI: 1.86 to 10.64) and failure of combined therapy with csDMARDs (OR: 2.42, 95% CI: 1.15 to 5.07). The increased body mass index was protective (OR:0.81, 95% CI: 0.75 to 0.87). Conclusions: Around one of four patients with RA presented muscle wasting. Muscle wasting is related to treatment failure of combined csDMARDs; other factors influencing the presence of muscle wasting is being postmenopausal, whereas, the body mass index was a protective factor. [ABSTRACT FROM AUTHOR]

Psoriatic arthritis (PsA) is an immune-mediated inflammatory disease with heterogeneity regarding its clinical features, mainly affecting the skin and the musculoskeletal system; additionally, extra-musculoskeletal manifestations and comorbidities are common, adding complexity to its treatment. In the last decades, a plethora of therapeutic options have been available, including conventional synthetic disease-modifying anti-rheumatic drugs (DMARDs), biological DMARDs (bDMARDs), and targeted synthetic DMARDs (tsDMARDs), and many recommendations have been published regarding the proper use of them in patients with PsA. In rheumatoid arthritis, the combination of conventional with bDMARDs or tsDMARDs is a common and recommended practice, whereas in PsA there is scarce data about the benefit of this combination. This review summarizes all the available data from randomized clinical trials, observational studies, and registries about the value of this therapeutic strategy., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2024.)

Objective: Conventional synthetic disease modifying antirheumatic drugs (csDMARDs) were recommended in 2019 as first line therapy from Italian Medicines Agency (AIFA) for the treatment of moderate to severe psoriasis. Updated local guidelines recommended methotrexate (MTX) as the drug of first choice. Nevertheless, MTX is reported by AIFA to be underused. Since no study evaluated jointly the first-line efficacy and costs of the most widely used biologic drugs (adalimumab, etanercept, secukinumab and ustekinumab) and methotrexate in Italy, a cost per responder (CPR) analysis was performed. Methods: A CPR model was developed based on efficacy data from a published Cochrane network meta-analysis.Drug costs included in the model were estimated based on average regional tender prices. The primary analysisassessed the CPR of both Psoriasis Area and Severity Index (PASI) 90 at weeks 12 and 52. A secondary analysis was conducted considering PASI 75. For methotrexate, both an average dosage of 13.4 mg, estimated by an expertpanel, and a dosage of 15 mg reported in European guidelines were considered. Results: At weeks 12 and 52, the costs per responder PASI 90 were lower for methotrexate 13.4 mg compared to the most widely used biologics in Italy, € 566.71 and € 2,455.72 respectively. Methotrexate also showed a lowest CPR both at 12 and 52 weeks, € 529.95 and € 2,296.47 respectively, in the secondary analysis. Conclusions: The analysis showed a lower cost per responder for methotrexate than for adalimumab, etanercept,secukinumab and ustekinumab. For healthcare budget holders, this means using the saved resources to treat more patients.

• Patients on triple csDMARD therapy (MTX+ HCQ+ SSZ) remained on treatment longer than patients on double csDMARD therapy (MTX+LEF). However, this difference was not statistically significant. • Compared to double csDMARD therapy (MTX+LEF), triple csDMARD therapy (MTX +HCQ+SSZ) was more likely to be associated with reaching low-disease activity including remission at 6 months after treatment initiation. • Female patients and patients with at least one comorbidity were more likely to discontinue therapy. • This study provides practical evidence that can be used in routine patient care. There are various combination conventional synthetic disease-modifying-antirheumatic drug (csDMARD) treatment strategies used in rheumatoid arthritis (RA). A commonly used csDMARD combination is triple therapy with methotrexate (MTX), sulfasalazine (SSZ) and hydroxychloroquine (HCQ). Another approach is double therapy with MTX and leflunomide (LEF). We compared the real-world retention of these two treatment combinations. Patients with RA from the Ontario Best Practices Research Initiative (OBRI) who received triple or double therapy on or after OBRI enrolment were included. Retention rates were compared between these two groups. We also analyzed which medication in the combination was discontinued and the reasons for treatment discontinuation. Disease activity was assessed at baseline, 6 and 12 months after treatment initiation as well as at time of discontinuation. Risk factors for treatment discontinuation were also examined. Six hundred and ninety-two patients were included (258 triple and 434 double therapy). There were 175 (67.8%) discontinuations in the triple therapy group and 287 (66.1%) discontinuations in patients on double therapy. The median survival for triple therapy was longer (15.1 months; 95% CI: 11.2–21.2) compared to double therapy (9.6 months; 95%CI: 7.03–12.2). However, this was not statistically significant. Disease activity at 6 and 12 months, measured by 28-joint count Disease Activity Score based on erythrocyte sedimentation rate (DAS28-ESR) was lower with triple therapy (mean DAS28 at 6 months 3.4 vs. 3.9, P < 0.0001 and at 12 months 3.2 vs. 3.5, P = 0.0005). Patients on triple therapy remained on treatment longer than patients on double therapy. However, this difference was not statistically significant. [ABSTRACT FROM AUTHOR]

The study aimed to compare treatment retention for first-line TNF inhibitor (TNFi) in the ATTRA registry patients receiving either combination with conventional synthetic DMARDs or TNFi as monotherapy. A retrospective multicenter study analyzed data of all adult patients with rheumatoid arthritis (n = 3032) starting TNF inhibitor as the first-line biological therapy in combination with csDMARDs or in monotherapy from January 1st 2012 to December 31st 2020. Kaplan–Meier method was employed to calculate drug retentions. Survival curves of treatment retentions were compared through Log-rank test between the studied subgroups. The hazard ratio for drug discontinuation was assessed through univariate cox regression models. In patients who started the first line TNFi therapy, the median treatment retention was 47.7 (42.2; 53.1) months for combination therapy and 22.7 (14.9; 30.6) months for TNFi monotherapy (p < 0.001). Estimated one-year survival was higher in patients on TNFi combined with csDMARDs as compared with TNFi monotherapy (75.3% vs 65.7%); two-year survival rate was 63.2% vs 49.2%, three-year survival rate was 55.4% vs 42.4% and five-year survival 44.9% vs 26.4% of patients. The estimated survival on the first TNFi was higher in patients taking combination therapy with methotrexate than with other csDMARDs (p = 0.003). Use of csDMARDs co-medication was associated with significantly better first TNFi drug survival compared to monotherapy. The combination of TNFi with MTX is more effective than the combination with leflunomide, which did not demonstrate a significant effect. [ABSTRACT FROM AUTHOR]

Objective: Conventional synthetic disease modifying antirheumatic drugs (csDMARDs) were recommended in 2019 as first line therapy from Italian Medicines Agency (AIFA) for the treatment of moderate to severe psoriasis. Updated local guidelines recommended methotrexate (MTX) as the drug of first choice. Nevertheless, MTX is reported by AIFA to be underused. Since no study evaluated jointly the first-line efficacy and costs of the most widely used biologic drugs (adalimumab, etanercept, secukinumab and ustekinumab) and methotrexate in Italy, a cost per responder (CPR) analysis was performed. Methods: A CPR model was developed based on efficacy data from a published Cochrane network meta-analysis. Drug costs included in the model were estimated based on average regional tender prices. The primary analysis assessed the CPR of both Psoriasis Area and Severity Index (PASI) 90 at weeks 12 and 52. A secondary analysis was conducted considering PASI 75. For methotrexate, both an average dosage of 13.4 mg, estimated by an expert panel, and a dosage of 15 mg reported in European guidelines were considered. Results: At weeks 12 and 52, the costs per responder PASI 90 were lower for methotrexate 13.4 mg compared to the most widely used biologics in Italy, € 566.71 and € 2,455.72 respectively. Methotrexate also showed a lowest CPR both at 12 and 52 weeks, € 529.95 and € 2,296.47 respectively, in the secondary analysis. Conclusions: The analysis showed a lower cost per responder for methotrexate than for adalimumab, etanercept, secukinumab and ustekinumab. For healthcare budget holders, this means using the saved resources to treat more patients. [ABSTRACT FROM AUTHOR]

Abstract Background The interleukin-6 receptor inhibitor sarilumab demonstrated efficacy in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or as monotherapy in patients with moderately to severely active rheumatoid arthritis (RA) with an inadequate response (IR) or intolerant (INT) to methotrexate (MTX) or tumour necrosis factor (TNF)-α inhibitors. This analysis investigated the efficacy and safety of sarilumab in patient subgroups. Methods Data were included from phase III studies: two placebo-controlled studies of subcutaneous sarilumab 150/200 mg every 2 weeks (q2w) either + MTX in MTX-IR patients (52 weeks) or + csDMARDs in TNF-IR/INT patients (24 weeks), and a monotherapy study of sarilumab 200 mg q2w vs. adalimumab 40 mg q2w in MTX-IR/INT patients (24 weeks). Prespecified and post hoc subgroups included patient demographics, disease characteristics, and prior treatments. Prespecified and post hoc endpoints included clinical, radiographic, and physical function measures, and p values are considered nominal. Safety was assessed during double-blind treatment. Results The superiority of sarilumab (either as monotherapy vs. adalimumab or in combination with csDMARDs vs. placebo + csDMARDs) across clinical endpoints was generally consistent across subgroups defined by patient demographics, disease characteristics, and prior treatments, demonstrating the benefit of sarilumab treatment for a wide range of patient types. Interaction p values of

Background: Muscle wasting, also known as myopenia, is frequent in rheumatoid arthritis (RA). To date, it is still unknown if the failure of pharmacologic therapies increases the risk of myopenia in RA. Objective: To identify if treatment failure with conventional synthetic DMARDs (csDMARDs) constitutes an independent risk factor of muscle wasting in women with RA. Methods: This was a cross-sectional study. We included 277 women with RA. Assessments in RA patients included: clinical, epidemiological, and therapeutic variables. The skeletal muscle index (SMI) was estimated by DXA, and myopenia was diagnosed if they had an SMI < 5.45 kg/m2. Multivariable logistic regression models identified risk factors of myopenia. Results: Muscle wasting was observed in 28.2% of patients with RA. The risk factors of myopenia in RA were menopausal (OR: 4.45, 95% CI: 1.86 to 10.64) and failure of combined therapy with csDMARDs (OR: 2.42, 95% CI: 1.15 to 5.07). The increased body mass index was protective (OR:0.81, 95% CI: 0.75 to 0.87). Conclusions: Around one of four patients with RA presented muscle wasting. Muscle wasting is related to treatment failure of combined csDMARDs; other factors influencing the presence of muscle wasting is being postmenopausal, whereas, the body mass index was a protective factor.

Objectives To quantify the prevalence of co-morbidities in patients with early RA and determine their prognostic value for effectiveness outcomes in a randomized trial. Methods We included patients from the 2-year pragmatic randomized CareRA trial, who had early RA (diagnosis < 1 year), were DMARD naïve and then treated-to-target with different remission induction schemes. Prevalence of co-morbidities was registered at baseline and the Rheumatic Diseases Comorbidity Index (RDCI; range 0–9) was calculated. We tested the relation between baseline RDCI and outcomes including disease activity (DAS28-CRP), physical function (HAQ index), quality of life (SF-36 domains) and hospitalizations over 2 years, using linear mixed models or generalized estimating equations models. Results Of 379 included patients, 167 (44%) had a RDCI of minimum 1. RDCI scores of 1, 2 or ≥3 were obtained in 65 (17%), 70 (19%), and 32 (8%) participants, respectively. The most frequent co-morbidity was hypertension (22%). Patients with co-morbidities had significantly higher HAQ (β  = 0.215; 95% CI: 0.071, 0.358), DAS28-CRP (β  = 0.225; 95% CI: 0.132, 0.319) and lower SF-36 physical component summary scores (β  =−3.195; 95% CI: −4.844, −1.546) over 2 years than patients without co-morbidities, after adjusting for possible confounders including disease activity and randomized treatment. Patients with co-morbidities had over time lower chances of achieving remission (OR = 0.724; 95% CI: 0.604, 0.867) and a higher risk of hospitalization (OR = 3.725; 95% CI: 2.136, 6.494). Conclusion At disease onset, almost half of RA patients had at least one clinically important co-morbidity. Having co-morbidities was associated with worse functionality and disease activity outcomes over 2 years, despite intensive remission induction treatment. Trial registration Clinical trials NCT01172639. [ABSTRACT FROM AUTHOR]

Rheumatic diseases occur commonly in patients of childbearing age. The compatibility of different Disease Modifying Anti-Rheumatic Drugs (DMARDs) during pregnancy and lactation can affect the management decision when treating these patients. With the development of promising biologics DMARDs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs) in various rheumatic diseases, their safety in pregnancy and lactation is an issue for both patients and clinicians. Recently, three different guidelines on the compatibility of DMARDs during pregnancy and lactation has been published by ACR, EULAR and BSR respectively. This article summarizes their recommendations on the management of patients on DMARDs during pregnancy and lactation.

Objectives Conventional synthetic DMARDs (csDMARDs) are the first-line treatment for PsA, but there is conflicting data regarding their efficacy and scarce reports describing the duration of use (drug retention) of csDMARD in this population. Their position in treatment recommendations is a matter of growing debate due to the availability of alternative treatment options with higher levels of evidence. We aimed to study drug retention and predictors for drug retention among PsA patients receiving first-line csDMARD monotherapy. Methods Retrospective cohort study in DMARD-naïve adult PsA patients in whom a first csDMARD was prescribed as monotherapy primarily to treat PsA-related symptoms. The main outcome was time to failure of the csDMARD (i.e. stopping the csDMARD or adding another DMARD). Results A total of 187 patients were included, who were mainly prescribed MTX (n  = 163) or SSZ (n  = 21). The pooled median drug retention time was 31.8 months (interquartile range 9.04–110). Drug retention was significantly higher in MTX (median 34.5 months; interquartile range 9.60–123) as compared with SSZ-treated patients (median 12.0 months; interquartile range 4.80– 55.7) (P  =0.016, log-rank test). In multivariable Cox regression, the use of MTX and older age were associated with increased retention. The main reasons for treatment failure were inefficacy (52%) and side effects (28%). Upon failure, MTX treated patients were more commonly, subsequently treated with a biologic DMARD compared with SSZ (P < 0.05). Conclusion MTX outperforms SSZ as a first-line csDMARD in DMARD-naïve PsA patients with respect to monotherapy drug retention in daily clinical practice. [ABSTRACT FROM AUTHOR]

Aims: With the arrival of conventional synthetic (csDMARDs), biological (bDMARDS) and then targeted synthetic (tsDMARDs) disease-modifying anti-rheumatic drugs, the therapeutic arsenal against rheumatoid arthritis (RA) has recently expanded. However, there are still some unmet needs for patients who do not achieve remission and continue to worsen despite treatments. Of note, most randomized controlled trials show that, for methotrexate-inadequate responders, only 20% of patients are ACR70 responders. With our better understanding of RA pathogenesis, finding new treatments is a necessary challenge. The objective of our study was to analyse the whole pipeline of immunosuppressive and immunomodulating drugs evaluated in RA and describe their mechanisms of action and stage of clinical development. Methods: We conducted a systematic review of all drugs in clinical development in RA, in 17 online registries of clinical trials. Results: The search yielded 4652 trials, from which we identified 243 molecules. Those molecules belong to csDMARDs (n = 22), bDMARDs (n = 118), tsDMARDs (n = 103). Twenty-four molecules are already marketed in RA in at least one country: eight csDMARDs, 10 bDMARDs and six tsDMARDs. Molecules under current development are mainly bDMARDs (n = 34) and tsDMARDs (n = 33). Seven of those have reached phase III. A large number of molecules (150/243, 61.7%) have been withdrawn. Conclusion: Despite the availability of 24 marketed molecules, the development of new targeted molecules is ongoing with a total of 243 molecules in RA. With seven molecules currently reaching phase III, we can expect an increase in the armamentarium in the years to come. [ABSTRACT FROM AUTHOR]

Background: Rituximab (RTX), an anti-CD 20 monoclonal antibody is one of the first line biological disease-modifying anti-rheumatoid drug indicated for the treatment of rheumatoid arthritis (RA) in patient's refractory to conventional Synthetic DMARDs (csDMARDs). Limited data are available about the safety and efficacy of biosimilar version of this molecule. In this study, we assessed the clinical efficacy and safety profile of biosimilar RTX, RedituxTM. Methods: In this prospective study, 36 adults with moderate disease activity measured by the European League Against Rheumatism (EULAR) disease activity score (DAS28-erythrocyte sedimentation rate [ESR] ≥3.2), who had failed conventional therapy with at least 2 csDMARDs were initiated on RTX, 1000 mg, given on day 0 and day 15, after taking informed consent. Biomarkers including ESR, C reactive protein, Immunoglobulin G and M (IgG, IgM) and DAS28-ESR scores were measured at baseline and repeated at 2, 4, 8, 12, 16, 20, and 24 weeks. The primary endpoint was attaining EULAR good/moderate response. Results: DAS28-ESR score showed a statistically significant decline at 24 weeks (P < 0.001). Seventy-five percent patients showed an EULAR moderate response while 25% showed no EULAR response at 24 weeks posttreatment. IgG and IgM levels declined by 24.9% (P < 0.001) and 37% (P = 0.020) at end of 24 wks. However, there were no infections noted during the period of study. The most common adverse event was infusion reaction seen in 16.6% of patients. Conclusions: RTX is a safe and effective drug for the management of seropositive RA with results comparable with the original molecule. No serious adverse effects were noted in the study except for mild infusion reactions and fall in immunoglobulin levels.

Purpose of review: During the last two decades, the therapeutic decisions and strategies for rheumatoid arthritis (RA) management have improved dramatically. Today, the therapeutic armamentarium is significantly augmented, and by using both old and new drugs, remission or low disease activity is a reasonable goal. The use of conventional synthetic (cs) disease-modifying anti-rheumatic drugs (DMARDs) in combination with biologic (b) or targeted synthetic (ts) DMARDs has revolutionized RA treatment. Methotrexate administration is considered fundamental among other csDMARDs for the treatment of RA. It is recommended as the initial drug (monotherapy), or in combination with other csDMARDs, bDMARDs, and tsDMARDs in a step-up strategy. Furthermore, it can be used with other csDMARDs as initial combination-therapy. On the other hand, despite the fact that bDMARDs and ts DMARDs are highly efficacious and can also be used as monotherapy in certain cases, cost-effectiveness is still questionable when compared with csDMARDs. In this direction, the classic argument of utmost importance has to do with the most appropriate treatment strategy that shall be initially applied: csDMARD combination-therapy versus monotherapy, or step-up combinationtherapy with bDMARDs, especially tumor necrosis factor-α (TNFa) blockers. For this reason, a literature review of the most important csDMARDs combination and bDMARDs combination studies has been deployed. Recent findings: The results showed that the triple csDMARDs therapy approach is more effective and less expensive. In addition, workers' productivity is higher than any other treatment options for RA. Summary: Triple-therapy constitutes a smart, efficacious, and significantly cheaper choice for RA therapeutic management. [ABSTRACT FROM AUTHOR]

The treatment of inflammatory arthritides has been changed dramatically in the past two decades with the introduction of the biological (b) disease-modifying anti-rheumatic drugs (DMARDs) as well as the targeting synthetic (ts) DMARDs that can be used as monotherapy or in combination with conventional synthetic (cs) DMARDs. The concept of treat to target (T2T) and tight control monitoring of disease activity represents a therapeutic paradigm of modern rheumatology. In rheumatoid arthritis (RA), this treatment approach has proven to be effective in many clinical trials and is now a well-established approach. The most common treatment strategies rely on the combination of csDMARDs (mainly methotrexate, sulfasalazine and hydroxychloroquine). This comes from different studies which compare the outcomes of combination therapies versus csDMARD monotherapy or versus methotrexate plus biologics in early RA patients. Here, we review the literature of the most important T2T studies for RA patients. The results showed that a tight control strategy appears to be more important than a specific drug to control RA. T2T approach aiming for remission or low disease activity can be achieved in early RA patients using less expensive drugs in comparison to newer drugs and this may need to be recognised in the future recommendations for the management of RA. Key Points: • Tight-control and treat-to-target (T2T) strategies are the cornerstone in achieving remission or low disease activity in rheumatoid arthritis (RA) • A plethora of clinical trials has confirmed the efficacy of csDMARDs when the tight-control and T2T strategies are applied • T2T and tight-control strategies are a less expensive option in comparison to newer drugs and may be recognised in the future recommendations for the management of RA. • Treatment decisions and strategies are more important than just the drugs. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to characterize disease burden among patients with rheumatoid arthritis (RA) with moderate-to-high disease activity who had received conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) monotherapy for ≥ 6 months but had not advanced to a biologic therapy. Methods: Patients enrolled in the US Corrona RA Registry between June 1, 2014, and January 30, 2018, with 6 months of continuous csDMARD monotherapy, with moderate-to-high disease activity, who remained biologic naive, and who had ≥ 1 follow-up visit were identified. Disease activity was assessed among patients with a 6-month follow-up visit (± 3 months). Descriptive statistics were used to compare demographics and disease characteristics between patients with or without treatment advancement. Results: The study included 409 patients with a disease activity assessment at 6 months (mean (SD) age 65.9 (12.6) years; mean duration of csDMARD therapy 407 (221) days). Of those patients, more than half (54%, n = 219) remained in moderate-to-high disease activity. Patients remaining in moderate-to-high vs. remission-to-low disease activity had higher baseline swollen (6.1) and tender joint counts (6.8). Over the 6-month period, treatment advancement occurred in 29% of patients. Those who advanced treatment (n = 118) vs. did not advance treatment (n = 291) were younger, had a shorter duration of RA, had higher disease activity, and reported higher levels of pain and fatigue. Conclusions: The substantial number of patients with persistent moderate-to-high disease on csDMARDs over a 6-month period and who did not advance treatment indicates that there is considerable need for a treat-to-target approach to care for patients with RA. Key Points •For patients with RA and an inadequate response to treatment with initial csDMARD monotherapy, guidelines recommend treatment advancement; however, this may not be occurring in real-world clinical settings. •In the current study, a substantial proportion of patients (54%) on csDMARDs had persistent moderate-to-severe disease activity at the 6-month (± 3 months) follow-up visit; however, only 29% of patients had their medication treatment advanced, indicating that there is considerable need for a treat-to-target approach to care for patients with RA. •Patients with younger age, shorter RA duration, and higher disease activity were more likely to have their medication treatment advanced, which suggests that potentially more aggressive treatment of disease activity is needed across the whole RA population. [ABSTRACT FROM AUTHOR]

Objectives: To investigate predictors of inadequate response to first conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) including methotrexate (MTX) in untreated rheumatoid arthritis (RA) patients in daily clinical practice. Methods: Inadequate response to MTX or other csDMARDs was defined as being not low disease activity at 12 months in more than 3 of 4 composite measures, and discontinuation or start of biologic DMARDs. The association between baseline factors and csDMARDs-IR was assessed by univariate and multivariate logistic regression analyses. Results: Four hundred and eleven and 146 patients were started on MTX and other csDMARDs, respectively; 218 patients were responsive to MTX, with a response rate of 47.0%. Tender joint count (TJC, 6 in 28joints, odds ratio [OR]=1.67, 95% confidence interval [CI] 1.06-2.64) and CRP (1.0mg/ dL, OR = 1.72, 95%CI: 1.10-2.70) at baseline were identified as predictors on multivariate logistic regression analysis. TJC (OR = 3.60, 95%CI: 1.29-10.00) was the factor identified as a predictor of the development of other csDMARDs-IR. Conclusion: In this observational study, patients with untreated RA at risk of inadequate response to MTX included those with a higher TJC and higher CRP, while a higher TJC was the only independent predictor of an inadequate response to csDMARDs other than MTX. [ABSTRACT FROM AUTHOR]

Objective In order to develop interventions to optimize MTX use for the treatment of RA we evaluated the rate of, reasons for and predictors of MTX non-adherence during the first 6 months of therapy. Methods The Rheumatoid Arthritis Medication Study (RAMS) is a prospective multicentre cohort study of incident MTX users in the UK. Prior to MTX commencement demographic, clinical and psychological data were collected. A weekly patient-completed diary recorded MTX dose, possible side effects and adherence over 26 weeks. The number of non-adherent weeks was calculated. Potential baseline predictors of ever non-adherence (⩾1 week non-adherent) during the first 6 months of MTX therapy were identified using logistic regression analyses. Results 606 patients with RA were included; 69% female, mean (s.d.) age 60 (13) years and DAS28 score 4.2 (1.2). Over the first 6 months following MTX initiation, 158 (26%) patients were ever non-adherent (71% intentional, 19% non-intentional, 10% unexplained) and mean (s.d.) number of non-adherent weeks was 2.5 (2.1). Multivariable predictors of ever non-adherence included DAS28 [odds ratios (OR) 1.1, 95% CI 1.0, 1.4], fatigue (OR 1.1, 95% CI 1.0, 1.2 per cm), ⩾2 comorbidities vs no comorbidities (OR 1.9, 95% CI 1.1, 3.5) and high medication concerns despite perceived need (OR 1.1, 95% CI 1.0, 1.1 per unit decrease in need/concern differential). Conclusion This is the largest study evaluating early intentional and non-intentional non-adherence to MTX, which has identified that patient beliefs and multi-morbidity strongly link with non-adherence. These findings can direct the design of and provide potential targets for interventions to improve patient adherence. [ABSTRACT FROM AUTHOR]

The impact of the Coronavirus disease 2019 (COVID-19) pandemic on autoimmune diseases (AID) patients has been an important focus. This study was undertaken to characterize the incidence, clinical manifestations and hospitalization among AID affected by COVID-19 and to analyze the association between immunomodulatory medication and these outcomes. Clinical, demographic, maintenance treatment, symptoms and disease course data and outcomes of AID patients with COVID-19 infection were assessed via an online survey tool and printed copy from 1 January till February 28, 2023. A total of 432 patients with AID were enrolled in the study. The results showed the most common conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) was hydroxychloroquine (HCQ). The usage of csDMARDs didn't increase the risk of COVID-19 infection. Patients who warranted hospitalization were significantly older. ILD was associated with higher hospitalization rate. No csDMARDs other than calcineurin inhibitor (CNI) was associated with increased risk of hospitalization. HCQ intake was associated with cough. Compared with no glucocorticoids (GCs) group, high doses of GCs were accompanied with higher proportion of gastrointestinal symptoms and tachycardia, lower proportion of sore throat and ageusia. GCs didn't provoke the COVID-19 infection in patients with AID, but chronic use of oral GCs was significantly more common in those requiring hospitalization, and higher dose of GCs were correlated with higher risk of hospitalization. 97 patients discontinued csDMARDs after infection, which resulted in an elevated risk of hospitalization. Meanwhile, withdrawal of csDMARDs was associated with higher odds of disease flare and lower proportion of remission than maintenance groups. Collectively, our analysis provides the evidence that maintenance treatment of csDMARDs may be more prudent for AID patients during COVID-19 pandemic., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background: Rituximab (RTX) provides significant clinical benefits in active rheumatoid arthritis (RA) patients with inadequate response to DMARDs and anti-TNF. There is no data regarding efficacy of RTX in seropositive Palindromic Rheumatism (PR), a forerunner of RA. Aim: To determine the efficacy and safety of RTX treatment in active PR patients exhibiting inadequate response to conventional synthetic DMARDs (csDMARDs). Methods: The retrospective study, over a period of 3 years, included seropositive (RF ± antiCCP) PR patients with inadequate control of PR (> 4 attacks per months) despite combination csDMARDs and were treated with RTX. All the patients were treated with an initial dose of 500 mg RTX and later with a second infusion after 2 weeks' period in those who did not achieve adequate/ complete disease control. Patients were continued on csDMARDS and retreated with RTX on relapse of symptoms. Results: Thirty-three seropositive PR patients with a mean age of 48.15 ± 14.2 years, mean disease duration of 68.4 ± 68.2 months, mean follow up period of 24.3 ± 10.8 months, were treated with RTX. 88% patients were on combination DMARDS and 79% patients were females. All patient achieved rapid and complete control of palindromic attacks with RTX. Fifteen patients had a relapse after a mean duration of 10.4 ± 5.5 months and needed repeat RTX infusions following which remission was achieved. None of the patients progressed to RA till the end of the follow-up. No serious adverse effects were recorded. Conclusion: RTX treatment could be effective in achieving disease control in active palindromic rheumatism not responding to csDMARDs. Key Points: • PR is thought to be a forerunner of RA and rituximab (RTX) has been found to be effective in RA. • Our study supports the hypothesis that B cells play an important role in the pathophysiology of PR and that the combination (RTX+ conventional drugs) can prevent the disease evolution into RA. • This 3-year retrospective study showed that rituximab was found to be effective in those who responded poorly to conventional drugs and remission was achieved in all patients. • Although it is a rare disease, we see palindromic rheumatism patients in India more often. As the symptoms are very debilitating in these patients, in those patients, not controlled on conventional drugs, rituximab offers newer promise in controlling the attacks and prevents further progression to RA. [ABSTRACT FROM AUTHOR]

Objectives This post hoc analysis of the TOZURA study programme evaluated the efficacy and safety of subcutaneous tocilizumab (TCZ-SC) as monotherapy or with concomitant conventional synthetic DMARDs (csDMARDs) in patients with RA categorized by baseline glucocorticoid (GC) use. Methods TOZURA was a multinational, open-label, single-arm, common-framework study programme (11 protocols, 22 countries) in patients with moderate to severe RA in whom csDMARDs or biologic therapies had failed or who were MTX naïve. Patients received once-weekly TCZ-SC 162 mg for ⩾24 weeks as monotherapy or in combination with csDMARDs and/or oral GC use (⩽10 mg/day prednisone or equivalent), which was to be continued unchanged for 24 weeks. Treatment subgroups were defined by baseline GC use and analysed for efficacy and safety. Results Of 1804 patients who received TCZ-SC, 145 received monotherapy + GC, 208 received monotherapy without GC, 730 received combination therapy + GC and 721 received combination therapy without GC. The median GC dose in both GC subgroups was 5 mg/day. The proportion of patients who achieved clinical remission, defined as DAS in 28 joints using ESR <2.6, increased similarly from baseline to week 24 in all subgroups. Improvements in patient-reported outcomes were similar in all subgroups. Overall adverse event profiles were generally similar between subgroups, with some slight numerical differences between GC and non-GC subgroups. Conclusion The incremental efficacy benefits of TCZ-SC as monotherapy and in combination with csDMARDs were similar between patients with and without previous and continued oral GC treatment, with generally similar safety profiles. Trial Registration ClinicalTrials.gov, http://www.clinicaltrials.gov, NCT01941940, NCT01941095, NCT01951170, NCT01987479, NCT01988012, NCT01995201, NCT02001987, NCT02011334, NCT02031471, NCT02046603, NCT02046616. [ABSTRACT FROM AUTHOR]

Purpose of Review: To review the effectiveness of remission induction strategies compared to single csDMARD-initiating strategies according to current guidelines in early RA. Recent Findings: Twenty-nine studies, heterogeneous on, e.g., specific treatment strategy and remission outcome used, were identified. Using DAS28-remission over 12 months, 13 (76%) of 17 remission induction strategies showed significantly more patients achieving remission. Pooled relative "risk" was 1.73 [95%CI 1.59–1.88] for bDMARD-based remission induction strategies and 1.20 [95%CI 1.03–1.40] for combination csDMARD-based remission induction strategies compared to single csDMARD-initiating strategies. When additional glucocorticoid "bridging therapy" was used in single csDMARD-initiating strategies, the higher proportion patients achieving remission in remission induction strategies was no longer statistically significant (pooled RR 1.06 [95%CI 0.83–1.35]). For other remission outcomes, results were in line with above. Summary: Remission induction strategies are more effective in achieving remission compared to single csDMARD-initiating strategies, possibly more so in bDMARD-based induction strategies. However, compared to single csDMARD-initiating strategies with glucocorticoids, induction strategies may not be more effective. [ABSTRACT FROM AUTHOR]

To investigate the effect of concomitant conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) with adalimumab or infliximab on maintaining serum drug and clinical outcomes after the first year of treatment in patients with rheumatoid arthritis (RA). Second, to assess the influence of methotrexate (MTX) dose on these outcomes. Ninety-two patients with RA starting infliximab (n = 67) or adalimumab (n = 25) tumor necrosis factor inhibitor (TNFi) with available drug levels and clinical improvement assessment (European League Against Rheumatism [EULAR] response) after 12 months were included. Patients were grouped according to concomitant csDMARD use: (i) TNFi monotherapy; (ii) TNFi+MTX; (iii) TNFi with csDMARDs other than MTX (TNFi+OD). Patients receiving MTX were also classified by dose as < 15 mg/week (TNFi+MTX<15) and ≥ 15 mg/week (TNFi+MTX≥15). Logistic regression analyses were employed. More TNFi+MTX patients had circulating serum TNFi at 12 months (71% TNFi+MTX vs. 20% TNFi+OD vs. 9% TNFi monotherapy). Of these, the probability of maintaining serum TNFi levels was twice (OR 2.3; p = 0.06) than that of patients without MTX. However, statistically significant results were observed only for the highest MTX dose (OR 4.9; p = 0.02). Most patients achieving good EULAR response were treated with TNFi+MTX (81%). The probability of achieving this response was three times higher in patients within the TNFi+MTX group (OR 3.4; p = 0.03); however, no differences were found with regard to MTX dose. The persistence of serum TNFi and the probability of achieving clinical response are influenced by MTX but not by OD in patients with RA treated with infliximab or adalimumab. [ABSTRACT FROM AUTHOR]

Biologic disease-modifying anti-rheumatic drugs (bDMARD) have transformed the treatment paradigm of chronic autoimmune rheumatic diseases (ARDs), but they are often associated with adverse drug reactions. The present study evaluated the frequency, characteristics and type of infections, other than tuberculosis (TB), in ARD patients receiving bDMARDs. The multicentre, cross-sectional, retrospective, observational study was conducted across 12 centers in Karnataka, India, between January to August 2016. The study included patients receiving bDMARD therapy for various ARDs. Outcome variables considered were any infection, minor infections and major infections, other than TB. Clinical variables were compared between infection and no infection group, and the increase in the likelihood of infection with respect to various clinical variables was assessed. The study involved 209 subjects with a median (range) age of 41 (16-84) years and male to female ratio of 0.97:1. A total of 29 (13.88%) subjects developed infection following bDMARD therapy, out of whom a majority had minor infection (n = 26). The likelihood of developing any infection was noted to be more in subjects receiving anti-TNF (golimumab, P = 0.03) and those on three or more conventional synthetic (cs) DMARDs (P < 0.01). Infection risk was higher in patients with systemic lupus erythematosus (P = 0.04), other connective tissue disease (P < 0.01) and in patients with comorbidities (P = 0.13). The risk of infection was associated with the use of anti-TNF therapy and more than three csDMARDs, co morbidities and Adds such as systemic lupus erythematosus and connective tissue disease. [ABSTRACT FROM AUTHOR]

Background: Technetium [99Tc] methylene diphosphonate injection (99Tc-MDP) is widely used for the treatment of rheumatoid arthritis (RA), but there is still insufficient evidence for its application. Through the utilization of meta-analysis and systematic reviews, this study aimed to evaluate the effectiveness and safety of 99 TC-MDP in combination with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) for RA., Methods: This study was registered on PROSPERO in advance (CRD42021220780). A systematic search was conducted in PubMed, Embase, the Cochrane Library, and multiple international public databases from their inception to April 2023 to identify clinical randomized controlled trials exploring the use of 99Tc-MDP combined with csDMARDs in the treatment of RA. Each outcome was subjected to meta-analysis, and the quality of evidence was assessed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The American College of Rheumatology's 50 %/70 % response criteria scores (ACR50/70) scores were utilized as the primary effectiveness outcomes, and risks were measured by assessing the rates of AEs. Moreover, secondary efficacy outcomes were evaluated, including the Disease Activity Score 28 (DAS28) and bone mineral density (BMD) as joint function indicators and the erythrocyte sedimentation rate (ESR) and interleukin-17 (IL-17) as inflammatory indicators., Results: In this meta-analysis, a total of 34 studies (2296 patients) were included out of 1149 retrieved studies. The summarized results showed that the treatment group treated with the combination of 99Tc-MDP and csDMARDs had significantly higher ACR50 (RR = 1.32, 95 % CI: 1.13-1.55, P = 0.0004) and ACR70 (RR = 1.40, 95 % CI: 1.07-1.82, P = 0.01) scores than the control group receiving csDMARDs alone. In addition, the overall incidence of AEs was lower with the combination of 99Tc-MDP and csDMARDs than with csDMARDs alone (RR = 0.75, 95 % CI: 0.60-0.93, P = 0.009), but the possibility of phlebitis was higher in the treatment group (RR = 4.15, 95 % CI: 1.04-16.50, P = 0.04). In addition, the combination of 99Tc-MDP and csDMARDs had advantages over csDMARDs alone in improving DAS28 (WMD = 1.56, 95 % CI: 0.86-2.25, P < 0.0001), BMD (SMD = 1.12, 95 % CI 0.46-1.78, P = 0.0008), ESR (SMD = 0.71, 95 % CI 0.45-0.97, P < 0.00001), and IL-17 (WMD = 5.82, 95 % CI 3.86-7.77, P < 0.00001). However, the above results might have been influenced by the 99Tc-MDP dosage, csDMARD category, and treatment duration. Combining methotrexate and leflunomide, administering continuous treatment for 24 weeks, or using 3 sets of 99Tc-MDP doses (16.5 mg) may be the optimal 99Tc-MDP treatment plan for RA., Conclusion: Compared with csDMARD therapy alone, the combination therapy with 99Tc-MDP is more effective for RA patients and is associated with a lower overall incidence of adverse events, although the possibility of phlebitis was higher. However, due to the inherent limitations of the included RCTs, high-quality clinical trials are still needed to further assess the effectiveness and safety of this combination therapy., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Objectives. The aim of this pooled analysis of the TOZURA study programme was to evaluate the efficacy and safety of subcutaneous tocilizumab (TCZ-SC) as monotherapy or in combination with conventional synthetic DMARDs (csDMARDs) in patients with moderate to severe RA who had an inadequate response to csDMARD or anti-TNF agent therapy or who were MTX naive. Methods. TOZURA is a multinational, open-label, single-arm, common-framework, phase 4 study programme (11 protocols, 22 countries). Patients received TCZ-SC 162 mg each week for ≥24 weeks, administered at the investigator's discretion, as monotherapy or in combination with a csDMARD. Efficacy, safety and immuno-genicity were evaluated; propensity score-based matching was used for between-group comparisons. Results. Of 1804 patients, 353 (19.6%) received monotherapy and 1451 (80.4%) received combination therapy. The 28-joint DAS using ESR (DAS28-ESR) in both groups decreased significantly from baseline to week 24 (mean change: monotherapy -3.40, combination therapy -3.46), with no significant difference between groups (P = 0.46). The proportion of patients who achieved DAS28-ESR or Clinical Disease Activity Index remission or ACR 20/50/70/90 responses was similar between groups. Overall, 13.9% of patients withdrew--6.2% for safety reasons and 1.6% for insufficient therapeutic response; 5.8% of patients experienced one or more serious adverse events [14.6/100 patient-years (PY)]; six deaths occurred (0.64/100 PY). Conclusion. In a common framework of 11 studies in 22 countries, this phase 4 study programme confirmed TCZ-SC's known efficacy and safety profile with comparable effects as monotherapy and in combination with csDMARDs. [ABSTRACT FROM AUTHOR]

Background: Rituximab (RTX), an anti-CD 20 monoclonal antibody is one of the first line biological disease-modifying anti-rheumatoid drug indicated for the treatment of rheumatoid arthritis (RA) in patient's refractory to conventional Synthetic DMARDs (csDMARDs). Limited data are available about the safety and efficacy of biosimilar version of this molecule. In this study, we assessed the clinical efficacy and safety profile of biosimilar RTX, Reditux™. Methods: In this prospective study, 36 adults with moderate disease activity measured by the European League Against Rheumatism (EULAR) disease activity score (DAS28-erythrocyte sedimentation rate [ESR] =3.2), who had failed conventional therapy with at least 2 csDMARDs were initiated on RTX, 1000 mg, given on day 0 and day 15, after taking informed consent. Biomarkers including ESR, C reactive protein, Immunoglobulin G and M (IgG, IgM) and DAS28-ESR scores were measured at baseline and repeated at 2, 4, 8, 12, 16, 20, and 24 weeks. The primary endpoint was attaining EULAR good/moderate response. Results: DAS28-ESR score showed a statistically significant decline at 24 weeks (P < 0.001). Seventy-five percent patients showed an EULAR moderate response while 25% showed no EULAR response at 24 weeks posttreatment. IgG and IgM levels declined by 24.9% (P < 0.001) and 37% (P = 0.020) at end of 24 wks. However, there were no infections noted during the period of study. The most common adverse event was infusion reaction seen in 16.6% of patients. Conclusions: RTX is a safe and effective drug for the management of seropositive RA with results comparable with the original molecule. No serious adverse effects were noted in the study except for mild infusion reactions and fall in immunoglobulin levels. [ABSTRACT FROM AUTHOR]

Amaç: Pulmoner romatoid nodül (PRN), kronik enflamatuvar multisistemik bir hastalık olan romatoid artritin (RA) önemli bir ekstra-artiküler tutulumudur. Bu çalışmanın amacı RA-tedavisinde konvansiyonel sentetik DMARD (csDMARD) ve biyolojik DMARD'ların (bDMARD) nodül gelişimi üzerindeki etkilerini incelemektir. Yöntem: ICD-10 koduna göre RA tanısı almış ve en az bir bilgisayarlı tomografi (BT) çekilen 4117 hasta dahil edildi. İlk olarak hastaların öyküsü, fizik muayenesi, radyografisi ve laboratuvarlarına göre RA teşhisi doğrulandı. Hastaların aldığı tedaviler sentetik ve biyolojik DMARD olarak kaydedildi. Toraks BT'leri deneyimli bir radyolog tarafından incelendi. Pulmoner romatoid nodül için dahil edilme kriterleri; en az iki BT'si olan hastalar çalışmaya dahil edilmiştir (soliter nodüller veya tüm nodüllerin boyutunun ≤5 mm küçük olması durumunda analize dahil edilmemiştir). Pulmoner nodülde değişiklik şu şekilde tanımlanmıştır; takipte boyut değişen nodüller, nodüllerin kaviteleşmesi. En büyük nodül dominant nodül olarak adlandırıldı. Daha sonra hastalar serolpozitiflik durumuna göre ikiye ayrıldı. Demografik bilgiler, nodül özellikleri ve nodüldeki değişimleri karşılaştırıldı. Bulgular: Yüz otuz beş RPN (89 kadın, %65,9) hastası dahil edildi. Hastalık süresi 148,8 (0,3-494) aydı. Cinsiyete göre gruplar arasında fark yoktu. Hastaların 106'sında (%78,5) RF ve/veya anti-CCP pozitifti. Seropozitif olan hastalarda bazal BT'de nodül sayısı daha fazlaydı (Tablo 1). Hastaların 37'si (%27,4) gelişmiş tedavi kullanıyordu. Gelişmiş tedavi alanlarda progresyon ve yeni kavitasyon daha sıktı (Tablo 2). 19,1 (ortanca 0,4-405) ay takip sonrasında 39/135 (%28,8) hastada nodülde progresyon olduğu görüldü. Anti-TNF kullanan hastalarda progresyon kullanmayanlara göre daha sıktı [17/32 (%53,1) vs. 27/103 (%26,2), p=0,001]. RTX kullananlarda daha sıktı [15/32 (%46,8) vs. 24/103 (%23,3), p=0,01]. Diğer gelişmişler tedavilerde progresyon açısından fark saptanmadı. Metotreksat kullanımında progresyon açısından fark saptanmadı. Sadece sentetik DMARD kullanan hastalarda nodülde progresyona kadar geçen süre daha uzundur (ortanca csDMARD: 114, bDMARDs: 42,6 ay), p=0,031). Sonuç: RA hastalarının 1,5 yıl takibinde yaklaşık %30 hastada pulmoner romatoid nodülde progresyon görülmüştür. Sadece sentetik DMARD kullananlarda progresyon daha azdır. Anti-TNF, rituksimab gibi ilaçların kullanımında progresyonun daha sık olması hastalık ciddiyeti ile ilgili olabilir, daha ileri çalışmalara gereksinim vardır. [ABSTRACT FROM AUTHOR]

To analyse efficacy and safety of tocilizumab in patients with rheumatoid arthritis (RA) and an inadequate response to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) and/or tumour necrosis factor (TNF) inhibitors of the Swiss and Austrian patients from the ACT-SURE study. This is a sub-analysis of RA patients from Switzerland and Austria, who participated in the international phase 3b, open-label, ACT-SURE study. Patients with an inadequate response to csDMARDs or TNF antagonists receiving 8 mg/kg of IV tocilizumab every 4 weeks during a 24-week time period were included into the study. Therapy with one or more csDMARDs could be continued as combination therapy with tocilizumab (Combo) or stopped, resulting in tocilizumab monotherapy (Mono), at the treating physician's discretion. These two patient groups were analysed in separate and compared. Overall, 107 (22 on Mono vs. 85 on Combo) patients were treated with tocilizumab. The percentage of patients with at least one adverse event was significantly lower in the tocilizumab combination (58.8%) as compared to the monotherapy group (81.8%, p = 0.0458). No differences in ACR20/50/70/90 response rates were observed between both treatment groups at week 24 (Mono 63.6, 40.9, 22.7, and 18.2% vs. Combo 61.2, 43.5, 25.9, and 10.6%). The median time to low disease activity (LDA) was significantly shorter in patients treated with tocilizumab combination therapy (Mono 9.1, Combo 7.9 weeks, log rank p = 0.038). In this post hoc regional sub-analysis of the ACT-SURE study, no differences for disease activity were found comparing the two patient groups at week 24. However, median time to LDA was statistically shorter in patients treated with tocilizumab combination therapy as compared to tocilizumab monotherapy. Consequently, adding tocilizumab to csDMARD therapy rather than changing to tocilizumab monotherapy may be, in our opinion, the safest strategy to reach maximum effect in RA patients with active disease despite treatment with csDMARD. csDMARDs can be withdrawn either immediately due to adverse events or after at least low disease activity has been reached. [ABSTRACT FROM AUTHOR]

Objective. To determine the effect of medical treatment on work disability in patients with active PsA in a real-world setting. Methods. Four hundred patients with active PsA commencing or switching to anti-TNF or conventional synthetic DMARD (csDMARD) were recruited to a multicentre UK prospective observational cohort study. Work disability was measured using the work productivity and activity-specific health problem instrument and peripheral joint activity was measured with the disease activity in PsA composite measure. Results. Four hundred patients were recruited, of whom 229 (57.25%) were working (of any age). Sixty- two patients of working age (24%) were unemployed. At 6 months there was a 10% improvement in presenteeism (P = 0.007) and a 15% improvement in work productivity (P = 0.001) among working patients commenced on csDMARDs (n = 164) vs a larger and more rapid 30% improvement in presenteeism (P < 0.001) and 40% improvement in work productivity (P < 0.001) among those commenced on anti- TNF therapy (n = 65). Clinical response was poor among patients commenced on a csDMARD (n = 272), with an 8.4 point improvement in disease activity in PsA (P< 0.001) vs those commenced on anti-TNF therapy (n = 121), who had a 36.8 point improvement (P < 0.001). Conclusion. We report significant and clinically meaningful improvements in both work disability and clinical outcomes after commencement of anti-TNF therapy in a real-world setting. Improvements in all outcomes among those commencing csDMARDs were slower and of a smaller magnitude. [ABSTRACT FROM AUTHOR]

Current data demonstrated that in patients with coronavirus disease-19 (COVID-19), there is a dysregulation of the immune system during the severe form of the disease. This dysregulation is expressed with an uncontrolled release of pro-inflammatory cytokines such as interleukin-1 (IL-1), IL-6, IL-17, tumour necrosis factor alpha (TNFa) and chemokines, associated with increased serum ferritin levels and other acute phase reactants. On the other side, these cytokines play a pivotal role in autoimmune rheumatic diseases (ARD), mostly in rheumatoid arthritis (RA) and the spondyloarthropathies. Patients affected with ARD represent a particular vulnerable group, considering that they may be in an immunocompromised status due to their ailment and its treatment on one side, but on the other side, they may be protected from their immunosuppressive therapy. To this end, we present five patients with RA treated with conventional synthetic (cs) disease-modifying anti-rheumatic drugs (DMARDs) and biologic (b) DMARDs who were affected from COVID-19 and we will try to give answers to the above hypothesis., (© 2022 The Mediterranean Journal of Rheumatology (MJR).)

Juvenile idiopathic arthritis (JIA) is a chronic inflammatory disease and an exclusion diagnosis that includes all forms of arthritis that persists for more than 6 weeks under the age of 16. Although there is not yet a cure for JIA, and recent advances in the therapeutic field have created a more hopeful present and future for the patients. In the past, therapies for JIA have depended on non-steroidal medication, conventional synthetic disease-modifying antirheumatic drugs and corticosteroids. However, over the last decades, the advent of biologic therapies in JIA contributed to the preservation of functional activity, control of pain, avoidance of joint damage, and extra-articular manifestations. Furthermore, over the last years, international institutions, such as the American College of Rheumatology, have released recommendations and guidelines for rheumatologists for optimal JIA management. All the above have revolutionized the treatment of JIA with promising outcomes. To this end, the relevant literature is reviewed and discussed appropriately., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objectives : To investigate predictors of inadequate response to first conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) including methotrexate (MTX) in untreated rheumatoid arthritis (RA) patients in daily clinical practice. Methods : Inadequate response to MTX or other csDMARDs was defined as being not low disease activity at 12 months in more than 3 of 4 composite measures, and discontinuation or start of biologic DMARDs. The association between baseline factors and csDMARDs-IR was assessed by univariate and multivariate logistic regression analyses. Results : Four hundred and eleven and 146 patients were started on MTX and other csDMARDs, respectively; 218 patients were responsive to MTX, with a response rate of 47.0%. Tender joint count (TJC, ≥6 in 28joints, odds ratio [OR] = 1.67, 95% confidence interval [CI] 1.06-2.64) and CRP (≥1.0 mg/dL, OR = 1.72, 95%CI: 1.10-2.70) at baseline were identified as predictors on multivariate logistic regression analysis. TJC (OR = 3.60, 95%CI: 1.29-10.00) was the factor identified as a predictor of the development of other csDMARDs-IR. Conclusion : In this observational study, patients with untreated RA at risk of inadequate response to MTX included those with a higher TJC and higher CRP, while a higher TJC was the only independent predictor of an inadequate response to csDMARDs other than MTX.

Background: Treatment of rheumatoid arthritis (RA) includes the use of conventional (cs), biologic (b) disease-modifying anti-rheumatic drugs (DMARDs) and oral, intramuscularly, intravenous, or intraarticular (IA) glucocorticoids (GCs). In this paper, we analysed whether a treat-to-target (T2T) strategy optimizing csDMARD, oral, and IA-GC treatment as an adjunct new therapy to a new certolizumab pegol (CZP) therapy improves the effectivity in RA patients. Methods: 43 patients with active RA (≥6 tender, ≥6 swollen joints, ESR ≥ 20 mm/h or CRP ≥ 7mg/L) despite csDMARD treatment for ≥ 3 months and naïve to bDMARDs were randomized to CZP (200 mg/2 weeks after loading with 400 mg at weeks 0–2–4) plus a treat-to-target strategy (T2T, n = 21), or to CZP added to the established csDMARD therapy (fixed regimen, n = 22). The T2T strategy consisted of changing the baseline csDMARD therapy (1) SC-methotrexate (dose: 15 ≥ 20 ≥ 25 mg/week, depending on the initial dose) ≥ leflunomide (20 mg/d) ≥ sulphasalazine (2 × 1000 mg/d) plus (2) oral GCs (prednisolone 20–15–12.5–10–7.5–5–2.5–0 mg/d tapered every five days) and (3) injections of ≤5 affected joints with triamcinolone. DMARD modification and an addition of oral GCs were initiated, depending on the achievement of low disease activity (DAS 28 < 3.2). The primary objective was defined as the ACR 50 response at week 24. Results: ACR 50 was achieved in 76.2% of the T2T, as compared to 36.4% of the fixed regimen patients (p = 0.020). ACR 20 and 70 responses were achieved in 90.5% and 71.4% of the T2T patients and 59.1% and 27.3% of the fixed regimen patients, respectively (p = 0.045 and p = 0.010, respectively). The adverse event rate was similar for both groups (T2T n = 51; fixed regimen n = 55). Conclusion: Treat-to-target management with the optimization of csDMARDs, oral, and IA-GCs of RA patients in parallel to a newly established CZP treatment was safe and efficacious in comparison to a fixed regimen of csDMARDs background therapy. [ABSTRACT FROM AUTHOR]