UNASSIGNED: Disease-modifying anti-rheumatic drugs (DMARDs) have improved the outcomes of patients with rheumatoid arthritis (RA). DMARDs are classified into three categories: conventional synthetic DMARDs, biological DMARDs (including biosimilars), and targeted synthetic DMARDs. DMARDs, by way of their effect on the immune system, are associated with increased risk of adverse events, including infections, malignancies, cardiovascular disease, gastrointestinal perforations, and other less common events.
UNASSIGNED: In this narrative literature review performed with searches of the PubMed database from 1 January 2010 through 1 January 2023, we compare the risk of safety events between DMARDs using data from both randomized clinical trials and observational studies.
UNASSIGNED: DMARD use in RA is associated with higher rates of serious infections, tuberculosis reactivation, opportunistic infections, and possibly malignancies. Specific biologic DMARDs and higher doses are associated with elevated risks of various adverse events (gastrointestinal perforations, thromboembolism, serious infection). Shared decision-making is paramount when choosing a treatment regimen for patients based on their own comorbidities. JAKi are the newest class of medications used for RA with robust safety data provided in clinical trials. However, more real-world evidence and phase-IV pharmacovigilance data are needed to better understand comparative safety profile of DMARDs in RA.

OBJECTIVE: To update an evidence base informing the 2024 JCR clinical practice guidelines (CPGs) for the management of rheumatoid arthritis (RA) in older adults.
METHODS: Four clinical questions (CQs) regarding efficacy and safety of drug treatment were evaluated, with CQ1 addressing methotrexate (MTX), CQ2 biological disease-modifying antirheumatic drugs (bDMARDs), CQ3 Janus kinase (JAK) inhibitors, and CQ4 glucocorticoids (GCs). Quality of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation system.
RESULTS: Observational studies confirmed a pivotal role of MTX in the treatment of older RA patients. The meta-analysis showed that tumor necrosis factor inhibitors and JAK inhibitors were unequivocally effective in older RA patients. No data indicated that bDMARDs were unsafe for older patients. No safety data for JAK inhibitor use in older patients were available. One randomized controlled trial demonstrated that long-term treatment with low-dose GCs increased risks of GC-associated adverse events. The certainty of overall evidence was very low for all CQs.
CONCLUSIONS: This systematic review provides the necessary evidence for developing 2024 JCR CPGs for managing older patients with RA. Continued updates on the evidence of JAK inhibitors and GC are desired.

OBJECTIVE: This study aims to evaluate the active and chronic lesions in sacroiliac joints and lumbar spine over a decade of TNFi therapy in patients with AS.
METHODS: The study enrolled patients with AS under treatment with a TNFi for over a decade. The patients underwent a new MRI scan of their lumbar spine and sacroiliac joint (SIJ). Two readers evaluated all images. Inflammation of SIJ (SIS), SIJ structural damage (SSS) including Fat Metaplasia, Erosions, Backfill and Ankylosis, and Spondyloarthritis Research Consortium of Canada Bone marrow edema (SPARCC) spine score were recorded.
RESULTS: In the study, 15 patients were included, with 80% being male. The mean age during their first MRI was 38.1 (± 11.9) years old, and the majority (86.7%) tested positive for HLA-B27. While TNFi improved both BASDAI and BASFI scores, there was a noticeable increase in MRI acute lesions in the SIJ over time, where the median score increased from 0 (0-4) to 3 (0-10) after ten years (p = 0.028). After a decade of treatment, the median SPARCC spine score also increased from 0 (0-9) to 5 (0-16), p = 0.093. Finally, it was observed that there was a significant positive correlation between ESR and SIS erosions in cases of chronic lesions (r = 0.819, p < 0.001).
CONCLUSIONS: While TNFi have significantly improved the treatment of AS, this study shows that acute lesions can still develop despite treatment. A personalized approach that adapts MRI assessment to each patient\'s specific requirements may help detect changes early and enable doctors to intervene promptly to prevent further damage.

(1) to describe the frequency of minimal disease activity (MDA) in a real-life psoriatic arthritis (PsA) cohort, (2) to longitudinally explore predictors of MDA; (3) to examine frequency and predictors of low disease activity (LDA) in patients with axial involvement (axPsA).
consecutive PsA patients in stable biological/targeted-synthetic Disease-Modifying Anti-Rheumatic Drugs (bDMARDs/tDMARDs) who attended our center were enrolled. Disease activity indices, including MDA and ankylosing spondylitis disease activity score-LDA (ASDAS-LDA) for axPsA, were evaluated at baseline and every 6 months, up to 36 months or bDMARDs/tsDMARDs discontinuation. Patients\' history, BMI, comorbidities - including osteoarthritis (OA) and fibromyalgia - were collected. Variables were compared between patients who achieved sustained MDA and those who did not. Multivariable generalized estimating equation (GEE) models were built to identify predictors of MDA and ASDAS-LDA over time. Data were expressed as beta coefficient (95%CI).
104 patients were enrolled, 54% males, mean age 55.7 years; 52% had axPsA. Across all evaluations, 52-61% reached MDA, and 17-24% achieved ASDAS-LDA. AxPsA, fibromyalgia, OA and BMI≥35 were less frequently observed in patients with sustained MDA. The GEE model confirmed the following factors were significantly and independently associated with MDA: age (Beta=-0.05), bDMARDs/tsDMARDs duration (Beta=+0.31), axPsA (Beta=-1.07), fibromyalgia (Beta=-3.35), OA (Beta=-1.87), BMI≥35 (Beta=-2.53). Age (Beta=-0.01), fibromyalgia (Beta=-2.03) and OA (Beta=-1.30) were also independently associated with ASDAS-LDA.
MDA is an attainable target in real-life. AxPsA represents a difficult-to-treat subset. Sustained MDA depends on disease features (axPsA) as well as patients\' characteristics (e.g. age, bDMARDs/tDMARDs duration, comorbidities).

OBJECTIVE: To investigate whether biological DMARDs affect the risk of aseptic loosening after total hip/knee arthroplasty (THA/TKA) in patients with RA.
METHODS: We retrospectively identified all patients suffering from RA who underwent THA/TKA at our academic centre between 2002 and 2015 and linked them with an existing prospective observational RA database at our institution. The risk of aseptic loosening was estimated using radiological signs of component loosening (RCL). A time-dependent Cox regression analysis was used to compare the risk of implant loosening between patients treated with traditional DMARDS and biological DMARDs, or alternately both over time.
RESULTS: A total of 155 consecutive total joint arthroplasties (TJAs) (103 TKA vs 52 THA) was retrospectively included in the study. Mean age at implantation was 59 ± 13 years. Mean follow-up time was 69 ± 43 months. Overall, 48 (31%) TJAs showed signs of RCL, with 28 (27.2%) RCLs occurring after TKA compared with 20 after THA (38.5%). A significant difference regarding the incidence of RCL between the traditional DMARDs group (39 cases of RCL, 35%) and the biological DMARDs group (nine cases of RCL, 21%) (P = 0.026) was observed using the log-rank test. This was also true when using a time-dependent Cox regression with therapy as well as arthroplasty location (hip vs knee) as variables (P = 0.0447).
CONCLUSIONS: Biological DMARDs may reduce the incidence of aseptic loosening after TJA in patients with RA compared with traditional DMARDs. This effect seems to be more pronounced after TKA than THA.

The aims of this systematic literature review (SLR) were to identify the effects of approved biological and targeted synthetic disease modifying antirheumatic drugs (b/tsDMARDs) on synovial membrane of psoriatic arthritis (PsA) patients, and to determine the existence of histological/molecular biomarkers of response to therapy. A search was conducted on MEDLINE, Embase, Scopus, and Cochrane Library (PROSPERO:CRD42022304986) to retrieve data on longitudinal change of biomarkers in paired synovial biopsies and in vitro studies. A meta-analysis was conducted by adopting the standardized mean difference (SMD) as a measure of the effect. Twenty-two studies were included (19 longitudinal, 3 in vitro). In longitudinal studies, TNF inhibitors were the most used drugs, while, for in vitro studies, JAK inhibitors or adalimumab/secukinumab were assessed. The main technique used was immunohistochemistry (longitudinal studies). The meta-analysis showed a significant reduction in both CD3+ lymphocytes (SMD -0.85 [95% CI -1.23; -0.47]) and CD68+ macrophages (sublining, sl) (SMD -0.74 [-1.16; -0.32]) in synovial biopsies from patients treated for 4-12 weeks with bDMARDs. Reduction in CD3+ mostly correlated with clinical response. Despite heterogeneity among the biomarkers evaluated, the reduction in CD3+/CD68+sl cells during the first 3 months of treatment with TNF inhibitors represents the most consistent variation reported in the literature.

OBJECTIVE: We evaluate the socioeconomic impact of treatment with biological and targeted synthetic disease-modifying antirheumatic drugs in Japanese patients with rheumatoid arthritis.
METHODS: We analysed data retrospectively from the prospective observational CorEvitas RA Japan Registry (March 2016-February 2020). Patients were categorised into paid workers (PWs) and home workers (HWs) and further based on drug classes. We assessed medication persistence, treatment outcomes, health care resource utilisation, and socioeconomic impact over 12 months, including direct (drugs and health care resource utilisation) and indirect (loss of productivity) costs.
RESULTS: Overall, 187 PWs and 114 HWs were identified. Over 12 months, medication persistence was high, treatment outcomes improved, and outpatient visits reduced in both groups. Following treatment initiation, direct costs increased, whereas indirect (loss of productivity) costs decreased in both groups. The unadjusted socioeconomic impact [Japanese yen (JPY)] increased across all drug classes in PWs (range: 29,700-151,700) and HWs (range: -28,700 to 83,000). Adjusted change in monthly socioeconomic impact was JPY 29,700-138,900 for PWs and JPY -28,000 to 92,800 for HWs.
CONCLUSIONS: In this study of Japanese patients with rheumatoid arthritis, the socioeconomic burden increased across patient groups and drug classes. The decrease in indirect (loss of productivity) costs partially offset the increase in direct costs.

UNASSIGNED: Patients with rheumatic diseases taking immunosuppressive medications might be at an increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Despite the effectiveness of using combined conventional and biological disease-modifying anti-rheumatic drugs(bDMARDs) in managing rheumatic diseases, there have been concerns that taking biological agents may have an additive effect on getting infected with COVID-19. This study evaluates the impact of taking biological agents on altering the chance of getting infected with SARS-CoV-2 in rheumatoid and lupus patients compared to traditional DMARDs.
UNASSIGNED: We carried out a cross-sectional survey study from February 2020 to January 2021 on patients diagnosed with lupus and rheumatoid arthritis disease. COVID-19 infection was confirmed by the presence of symptoms and signs of the disease and para-clinical findings such as lymphopenia and elevated C-reactive protein (CRP) and positive chest CT scan or polymerase chain reaction (PCR) of COVID-19.
UNASSIGNED: Out of 591 patients included in this study, 422 (71.4%) had rheumatoid arthritis (RA), and 169 (28.6%) had systemic lupus erythematosus (SLE). Among them, 56 (9.5%) cases were diagnosed with COVID-19 infection. No association was found between age, gender, or type of rheumatological diseases and SARS-CoV-2. There was a significant association between COVID-19 infection and treatment with biological drugs (P-value<0.05) regardless of the type of rheumatologic disease. Interestingly, the analysis revealed that the type of biologic drug also altered the chance of COVID-19 infection; In fact, patients who took TNF inhibitors were significantly at a higher risk of disease than those taking Rituximab (P-value=0.000). Identical results were observed among RA patients (P-value<0.001), however, all 5 (3%) lupus cases treated with Rituximab infected with covid 19.
UNASSIGNED: This study develops a better understanding of the risk of immunosuppressive medications for SARS-CoV-2 infection. Patients treated with conventional and biological medicine had a higher disease risk than those taking exclusively conventional drugs. However, more studies are required to deliberate the relation of the reviewed factors with the severity of COVID-19.

OBJECTIVE: We aimed to investigate factors associated with impaired physical function [defined as Health Assessment Questionnaire Disability Index (HAQ-DI) >0.5] of old-old (aged 75-84 years) patients with rheumatoid arthritis.
METHODS: Data from 15,185 rheumatoid arthritis patients in the National Database of Rheumatic Disease in Japan were extracted from 2017 to 2018. We enrolled 3708 patients aged 55-84 years in Simplified Disease Activity Index (SDAI) ≤11 and Steinbrocker Stage I/II. Factors associated with HAQ-DI >0.5 were analysed by multivariable logistic regression.
RESULTS: About half of the old-old patients received methotrexate, which was lower than middle-aged (55-64 years) and young-old patients (65-74 years). The proportion of glucocorticoids in the old-old patients was highest among the three groups, and biological disease-modifying antirheumatic drugs were similarly used. The prevalence of HAQ-DI >0.5 was significantly higher in old-old patients with low disease activity than in those with remission. The same was true in the middle-aged and young-old patients. Multivariable analysis showed age, higher SDAI, glucocorticoid use, and methotrexate nonuse were significantly associated with HAQ-DI >0.5 in the old-old patients.
CONCLUSIONS: Achieving SDAI remission was an ideal goal for old-old patients in terms of physical function. Glucocorticoids and a low proportion of methotrexate use may influence the physical function of old-old patients.

UNASSIGNED: Previous studies showed a discrepancy between health-care professionals\' (HCPs\') and patients\' perspective on adverse drug reaction (ADR) burden. However, it is unclear which factors make an ADR burdensome. We aimed to give insight into why ADRs are perceived as burdensome by inflammatory rheumatic disease (IRD) patients, and whether this differs from the HCPs\' perspective.
UNASSIGNED: A qualitative study was conducted using Dutch Biologic Monitor data. Participants received bimonthly questionnaires on experienced ADRs attributed to biological DMARDs and were asked to elaborate on ADR burden using a Likert-type scale and an open-ended question for clarification. Data of 440 IRD patients were analyzed following thematic analysis. A similar analysis was done with semi-structured interviews with 13 HCPs.
UNASSIGNED: We identified seven themes associated with ADR burden: \'effect on medication prescription,\' \'impact on appearance,\' \'impact on autonomy,\' \'impact on daily life,\' \'psychological consequences,\' \'distressing aspects of ADR,\' and \'physical consequences.\' Identical themes were identified by HCPs, although they identified most subthemes in \'psychological consequences,\' and less subthemes in \'impact on daily life\' and \'impact on autonomy.\'
UNASSIGNED: Patients describe perceived ADR burden in both physical and psychological themes. The HCPs\' perspective is comparable, but mostly focuses on psychological impact.