Conventional Synthetic DMARDs Research Articles

Head-to-head studies on radiographic progression in axial spondyloarthritis

In this review article four clinical comparative studies in axial spondylarthritis (axSpA) are presented and discussed. SURPASS as the only head-to-head study investigated the effect of adalimumab biosimilar disease-modifying antirheumatic drug (bsDMARD) or secukinumab on radiographic progression over a time period of 2 years. Overall, the radiographic progression of the spine was low and no significant difference between adalimumab bsDMARD or secukinumab was noted. The three other studies were not constructed as direct head-to-head studies but compared the efficacy of non-steroidal antirheumatic drugs (NSARD) with and without simultaneous treatment with biological DMARDs (bDMARD). The CONSUL study showed no statistically significant difference in the delay of radiographic progression of the spine over 2 years in radiographic axSpA (r-axSpA) patients, who underwent either combined treatment with golimumab and celecoxib or treatment with golimumab alone over 2 years. The ESTHER study showed that patients with early axSpA active inflammatory lesions, which were detected by whole-body magnetic resonance imaging (MRI), showed a significantly greater improvement under treatment with etanercept than those treated with sulfasalazine. The INFAST study showed that patients with early active axSpA who received a combined treatment of infliximab and naproxen, achieved a clinical remission twice as frequently as those who only received naproxen. Therefore, for the endpoint of radiological progression no difference could be shown in the inhibition of radiological progression between the mechanisms of action investigated. The comparative data for the endpoint of clinical efficacy showed that patients with bDMARDs showed a clearly better response to treatment than patients with NSAR or conventional synthetic DMARDs (csDMARD).

Novel insights into the management of rheumatoid arthritis: one year in review 2024.

New evidence from 2023 has slightly shifted some perspectives on rheumatoid arthritis (RA) management. Glucocorticoids have reaffirmed their role as bridging therapy, while novel studies on JAK inhibitors have examined efficacy, mechanism of action, and their potential in high-risk populations, bolstering our understanding with real-world data.Additionally, among treatment strategies, achieving low disease activity has emerged as comparable to achieving remission in the long term, and new insights have been gained regarding tapering both biological and conventional synthetic DMARDs. Furthermore, novel approaches have been proposed for managing difficult-to-treat RA and pre-RA. In this paper, the reviewers aim to present the most relevant studies published during the last year in the field of RA management.

2023 Management Recommendations of Bangladesh Rheumatology Society on Pharmacological Treatment of Rheumatoid Arthritis With Synthetic and Biologic Disease-Modifying Drugs.

Rheumatoid arthritis (RA) is the most common inflammatory polyarthritis in Bangladesh. Bangladesh Rheumatology Society (BRS) proposes these management recommendations to treat the considerable burden of RA in the resource-constrained situation based on the best current evidence combined with societal challenges and opportunities.BRS formed a task force (TF) comprising four rheumatologists. The TF searched for all available literature, including updated American College of Rheumatology (ACR), European Alliance of Associations for Rheumatology (EULAR), and Asia-Pacific League of Associations for Rheumatology (APLAR) and several other guidelines, and systematic literature reviews until October 2023, and then a steering committee was formed, which included rheumatologists and internists. We followed the EULAR standard operating procedures to categorize levels of evidence and grading of recommendations. This recommendation has two parts -- general (diagnosis of RA, nomenclature of disease-modifying anti-rheumatic drugs [DMARDs], disease activity indices) and management portion. The TF agreed on four overarching principles and 12 recommendations. Overarching principles deal with early diagnosis and disease activity monitoring. Recommendations 1-5 discuss using glucocorticoids, NSAIDs, and conventional synthetic DMARDs (csDMARD). Recommendations 6-9 stretch the use of targeted synthetic DMARDs (tsDMARDs) and biological DMARDs (bDMARDs). The suggested DMARD therapy includes initiation with methotrexate (MTX) or another csDMARD (in case of contraindication to MTX) in the first phase and the addition of a tsDMARD in the second phase, switching to an alternative tsDMARDs or bDMARDs in the subsequent phases. The TF included the Padua prediction score for the thromboembolism risk estimation. Recommendations 10-12 cover infection screening, vaccination, and DMARD tapering. Bangladesh has a higher prevalence of RA. This recommendation will serve as a tool to treat this high burden of patients with RA scientifically and more effectively.

Treatment Patterns of Biologic Disease-Modifying Antirheumatic Drugs and Janus Kinase Inhibitors in Patients with Rheumatoid Arthritis in Japan: A Claims-Based Cohort Study.

Reports on treatment patterns of biologic disease-modifying antirheumatic drugs (bDMARDs)/Janus kinase inhibitors (JAKi) for rheumatoid arthritis (RA) in clinical practice are still sparse in Japan, especially in combination with conventional synthetic DMARDs (csDMARDs). The aim of this study was to investigate treatment patterns of bDMARD/JAKi in the treatment of RA in real-world clinical practice in Japan. A retrospective cohort study was conducted using the Japanese Medical Data Vision health claims database. The inclusion criteria required a recorded diagnosis of RA, defined by ICD-10 codes, in patients aged 18 years and older on the index date. We analyzed 39,903 RA patients treated with DMARDs from 2008 to 2020. Among analyzed subjects, 10,196 patients (25.6%) were prescribed bDMARDs/JAKi in combination with csDMARDs, and 3067 patients (7.7%) were prescribed these drugs without csDMARDs. Among the bDMARDs/JAKi, tumor necrosis factor inhibitors (TNFi) were the most commonly prescribed DMARD overall, and also the most common first-line therapy, accounting for 60.0% or 45.5% of patients prescribed these drugs in combination with or without csDMARDs, respectively. Switching, temporary discontinuation (restarting with the same agents), and discontinuation of bDMARDs/JAKi were observed in 3150 (30.9%), 1379 (13.5%), and 2025 (19.9%) patients with csDMARDs, and in 849 (27.7%), 513 (16.7%), and 833 (27.2%) patients without csDMARDs, respectively. Real-world treatment trajectories of bDMARDs/JAKi with and without csDMARDs was analyzed in RA patients in Japan between 2008 and 2020. TNFi were the predominant first-line therapy, and likely to be switched to different classes. Understanding the current treatment patterns, including discontinuation, is important to find an optimal treatment strategy for RA patients.

Cancer risk with tocilizumab/sarilumab, abatacept, and rituximab treatment in patients with rheumatoid arthritis: a Danish cohort study.

To investigate cancer risk in rheumatoid arthritis (RA) patients treated with tocilizumab/sarilumab, abatacept, or rituximab compared with those who received tumour necrosis factor inhibitors (TNFi) and compared with biological disease-modifying anti-rheumatic drugs (bDMARD) naïve RA patients. Nationwide registry-based cohort study of RA patients initiating treatment with tocilizumab/sarilumab, abatacept, rituximab, TNFi, and bDMARD-naive patients their second type of conventional synthetic DMARD (csDMARD). Patients were identified in DANBIO and followed for cancer from 2006-2020. Patients could contribute multiple treatments, with person years (PYRS), deaths, and cancers allocated to each treatment group in a 'latest type of treatment' manner. Inverse probability of treatment weighting and weighted cause-specific Cox models were used to calculate hazard ratios (HRs) for cancer in each tocilizumab/sarilumab, abatacept, and rituximab group compared with TNFI and bDMARD naïve groups, respectively. In total, 21 982 treatment initiations, 96 475 PYRS, and 1423 cancers were identified. There were no statistically significant increased HRs for overall cancer in tocilizumab/sarilumab, abatacept, or rituximab treatment groups (HRs ranged from 0.7-1.1). More than five years of abatacept exposure showed a non-significantly increased HR compared with TNFi (HR 1.41, 95% confidence intervals CI 0.74-2.71). For hematological cancers, rituximab treatment showed non-significantly reduced HRs: vs TNFi (HR 0.09; 95%CI 0.00-2.06) and bDMARD-naïve (HR 0.13; 95%CI 0.00-1.89). Treatment with tocilizumab/sarilumab, abatacept, or rituximab in RA patients was not associated with increased risks of cancer compared with TNFi-treated and with bDMARD-naïve RA patients in a real-world setting.

The Evaluation of Effectiveness and Safety of Guselkumab in Patients with Psoriatic Arthritis in a Prospective Multicentre "Real-Life" Cohort Study.

Guselkumab is an interleukin-23 (IL-23) inhibitor licensed for the treatment of psoriatic arthritis (PsA). This study aimed to evaluate the 6-month effectiveness of guselkumab in patients with PsA in a "real-life" multicentre patient cohort. We also estimated the drug retention rate (DRR) of gusulkumab, also assessing the impact of comorbidities and patient clinical characteristics, in a collective 18-month prospective follow-up. Between December 2021 and September 2023, consecutive patients with PsA were evaluated if treated at least for 6months with guselkumab in a prospective multicentre study to evaluate the effectiveness of the drug by means of disease activity index for psoriatic arthritis (DAPSA) and cumulative DRR. A total of 111 patients with PsA were evaluated and treated with guselkumab (age 56.8 ± 9.9, male sex 20.7%). These patients were mainly characterised by active and long-standing PsA with median disease duration of 6.0 (7.0) years (55.9% disease duration ≥ 5years), 55.0% showed comorbidities, 78.4% of patients were previously treated with biologic disease-modifying anti-rheumatic drugs (bDMARDs), and 60.4% concomitantly with conventional synthetic DMARDs (csDMARDs). After 6months, a significant reduction of DAPSA was observed (β - 15.47, p = 0.001, 95%CI - 23.15 to - 9.79) with 39.6% of patients achieving a DAPSA ≤ 14. At the end of cumulative follow-up, 71.2% of patients were still treated with guselkumab whereas 24.3% discontinued the drug because of inefficacy. An 18-month DRR of guselkumab of 66.7% was estimated with a mean time of administration of 9.8 ± 4.1months. The results of the DRR were stratified according to patient clinical characteristics. The DRR of guselkumab appeared to be not influenced by long disease duration, comorbidities, obesity, concomitant csDMARDs, and previous bDMARDs. The "real-life" 6-month effectiveness of guselkumab was shown in patients with PsA, mainly characterised by active long-standing disease, previously treated with bDMARDs, and with comorbidities. Furthermore, a good DRR of guselkumab was estimated in the cumulative 18months of follow-up and appeared to be not influenced by long disease duration, comorbidities, obesity, and previous bDMARDs.

The impact of COVID-19 and other factors on the usage status of the biologic drug therapies for rheumatoid arthritis: A study from Vietnam

ObjectivesTo describe the status of using biological Disease Modifying Anti Rheumatic Drugs (bDMARDs) to treat rheumatoid arthritis (RA) and related factors. In addition, the study determined the impact of COVID-19 on the usage of bDMARDs. MethodsThis is a cross-sectional study and included 219 RA patients over 18 years old. The Kaplan–Meier method and the log-rank test (p<0.05) were used to estimate the retention time and compare between different times. Cox regression analysis was used to determine the factors affecting the retention time of biological drugs (p<0.05). ResultsOut of 1967 courses of treatment, there were 149 (7.6%) drug discontinuations, 760 (38.6%) doses extensions and 64 (3.3%) drug switch. Moderate disease level and choosing tumor necrosis factor (TNF) inhibitors initially were associated with retention time of COVID-19. Drug discontinuations and dose extensions increased after COVID-19 emergence. The retention time during COVID-19 was significantly different from that of pre-COVID-19. Gender, type of first-used bDMARD, conventional synthetic DMARDs (csDMARDs) and corticoid usage status, disease activity levels were associated with retention time. ConclusionThe presence of COVID-19 has a significant effect on usage status of the biologic drug. Further longitudinal studies are needed to clarify the relationship between COVID-19 and drug usage as well as related factors.

Impact of treatment of rheumatoid arthritis on periodontal disease: A review.

Numerous studies support a bidirectional association between rheumatoid arthritis (RA), a chronic autoimmune degenerative inflammatory joint disease, and periodontitis, a chronic inflammatory disease caused by the immune reaction to bacteria organized in biofilms. RA and periodontitis are both multifactorial chronic inflammatory diseases that share common modifiable and non-modifiable risk factors. There is no cure for RA; treatment is based on lifestyle modifications and a variety of medications: nonsteroidal anti-inflammatory drugs (NSAID), glucocorticoids, and disease-modifying antirheumatic drugs (DMARDs, e.g., conventional synthetic DMARDs [csDMARDs]; biological DMARDs [bDMARD] and targeted synthetic DMARDs). There are molecular pathways of inflammation that are common to both RA and periodontitis. Thus, there is a potential effect of RA treatments on periodontitis. This systematic review aims to assess the impact of antirheumatic agents on periodontal conditions of patients suffering from both RA and periodontitis. PubMed/MEDLINE, Cochrane Library, and Embase online databases were systematically explored, and a manual search was performed to identify relevant studies published until January 2023. This review is registered in the PROSPERO database (CRD42023409006). A total of 2827 articles were identified, and 35 fulfilled the inclusion criteria. The included studies generally show a consensus that, at normal dosage, NSAID and corticosteroids have negligible impact on periodontium. Similarly, csDMARD alone or in combination with other csDMARD demonstrated no adverse effect on periodontium. Monotherapy with bDMARD had a positive effect on periodontal pocket depths and gingival inflammation in the longitudinal studies up to 6 months but showed negligible effect on the periodontium in interventional studies with a longer follow-up (9 months and 15.1 months). However, the combination of tumor necrosis factor (TNF)-α inhibitors+methotrexate (MTX) was associated with a rise in gingival inflammation. Due to the considerable heterogeneity of the study designs, a meta-analysis could not reasonably be performed. Within the limitations of the available studies, there is evidence to suggest that bDMARD monotherapy may improve the periodontal condition of RA patients with periodontal disease to a certain extent; the concomitant medication of TNF inhibitor+MTX could worsen gingival inflammation. More data are required to understand the impact of RA therapies on periodontal health.

Correlation Of Lipid Profile and Das28 Score of Early Rheumatoid Arthritis Patients on Conventional Synthetic Dmards

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation and a higher risk of cardiovascular diseases. The relationship between RA disease activity, lipid profiles, and the impact of disease-modifying antirheumatic drugs (DMARDs) on these parameters is an area of ongoing research. Objective: This study aimed to investigate the correlation between lipid profiles and the Disease Activity Score in 28 joints (DAS-28) in patients with early RA who were on conventional synthetic DMARDs. Methods: In this cross-sectional study, 30 RA patients from a rheumatology department were enrolled over six months. The study included adults aged 30-70 years, of both genders, who had been on DMARDs for at least 6 months. Exclusion criteria included fracture of the affected joint, pregnancy, use of steroids or lipid-lowering agents, and heavy smoking. Data on demographics, disease duration, type of DMARDs, and lipid profiles were collected. The DAS-28 score was calculated for each patient. Statistical analysis was performed using SPSS Version 25, with Pearson’s Correlation coefficient used to measure relationships between variables. Results: The cohort consisted of 53.3% males and 46.7% females, with a mean age of 48.23 years. The majority (76.7%) were rheumatoid factor positive. The most commonly used DMARD was Methotrexate (46.7%). The study found strong negative correlations between DAS-28 scores and lipid levels: total cholesterol (Pearson's r = -0.837), triglycerides (r = -0.759), LDL (r = -0.720), and HDL (r = -0.689). BMI showed a significant positive correlation with DAS-28 (r = 0.711). A notable negative correlation was observed between the duration of DMARD use and DAS-28 scores (r = -0.777). Conclusion: The study indicates a significant correlation between lipid profiles and disease activity in RA patients on DMARDs. The findings suggest that effective RA management with DMARDs could influence lipid metabolism and potentially reduce cardiovascular risks. These insights are crucial for developing comprehensive RA treatment strategies that encompass both joint health and cardiovascular considerations.

Increased risk of malignancy in HLA-B27-positive patients with ankylosing spondylitis requiring biologics for sustained inflammation: A long-term, single-center retrospective study.

To assess the link between the administration of biologic disease-modifying antirheumatic drugs (bDMARDs) and the risk of malignancy in human leukocyte antigen B27 (HLA-B27)-positive patients with ankylosing spondylitis (AS) experiencing sustained inflammation. Between 2006 and 2021, 1445 HLA-B27-positive patients with AS were retrospectively evaluated. Among them, 112 patients required bDMARD therapy. The study compared conventional therapy with bDMARDs and investigated the risk factors for developing malignancies. During 8253 patient-years of follow-up, 38 (2.6%) patients developed various malignancies, including lung, liver, breast, and colon cancer. The risk of malignancy was significantly higher in the bDMARD-treated group compared to PS-matched groups receiving conventional synthetic DMARDs (csDMARD) and non-steroidal anti-inflammatory drugs. The cumulative risk of malignancies increased significantly after 6 years of follow-up. All patients who developed malignancy after bDMARD therapy received tumor necrosis factor-α inhibitors. Requiring bDMARD therapy, requiring bDMARDs in combination with csDMARD therapy, and being diagnosed with AS after 30 years of age were independent risk factors for developing malignancy. HLA-B27-positive AS patients with sustained inflammation requiring biologic therapy, particularly if diagnosed after age 30, may have an increased risk of malignancy. Regular cancer screenings are advisable for these patients while undergoing biologic treatment.

No Waning of Pneumococcal Vaccine Responses over Time in People with Inflammatory Arthritis: Findings from a Single Centre Cohort.

Vaccination against pneumococcus reduces the risk of infective events, hospitalisation, and death in individual with inflammatory arthritis, particularly in those on immunomodulating therapy who are at risk of worse outcomes from pneumococcal disease. The objective of this study was to investigate the serological protection following vaccination against pneumococcal serovars over time. Methods: This was a single centre, retrospective cohort study of individuals with rheumatoid arthritis, psoriatic arthritis, or axial spondylarthritis who had previously received the PPSV23 polysaccharide pneumococcal vaccine (Pneumovax). Data were retrieved between January 2021 to August 2023. Dates of previous pneumococcal vaccination were identified using linked primary care records. Serum serotype levels were collected. The primary outcome was serological response defined as a titre ≥0.35 mcg/mL in at least five from a total of 12 evaluated pneumococcal serovars, examined using a Luminex platform. Multivariate logistic regression models adjusting for age, gender, ethnicity, co-morbidities, and the use of prednisolone, conventional synthetic and biological DMARDs were used to determine the odds of a sustained serological response according to time categorised into ≤5 years, 5-10 years, and ≥10 years since vaccination. Results: Serological response was measured in 296 individuals with inflammatory arthritis, with rheumatoid arthritis the most common diagnosis (74% of patients). The median time between pneumococcal vaccine administration and serological assessment was 6 years (interquartile range 2.4 to 9.9). A positive serological response to at least 5 serovars was present in 195/296 (66%) of patients. Time since vaccination did not significantly associate with serological protection compared with those vaccinated <5 years, the adjusted ORs of vaccine response was 1.15 (95% CI 0.64 to 2.07) in those 5-10 years and 1.26 (95% CI: 0.64 to 2.48) in those vaccinated over 10 years ago. No individual variable from the multivariate model reached statistical significance as an independent predictor of vaccine response, although steroid use at the time of vaccine had a consistent detrimental impact on serological immunity. Conclusions: We demonstrated that antibody titres following vaccination against pneumococcal serovars do not appear to wane over time. It appears more critical to focus on maximising the initial vaccine response, which is known to be diminished in this patient population.

Risk factors for interstitial lung disease in rheumatoid arthritis: a cohort study from the KOBIO registry

Background: Interstitial lung disease (ILD) is a critical extra-articular manifestation of rheumatoid arthritis (RA). However, little is known about the risk factors of RA-ILD. Objectives: Here, we examined the effect of demographic, clinical, therapeutic, and environmental factors on the incidence of ILD in RA patients using the Korean College of Rheumatology Biologics and Targeted Therapy (KOBIO) registry. Design: We used data from the KOBIO registry, a multi-center, prospective, observational cohort that included RA patients in South Korea. Methods: RA patients who used biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) or conventional synthetic (cs)DMARDs, and were enrolled in the KOBIO registry, were examined. Demographic, clinical, and radiographic characteristics, as well as medications, were recorded at baseline and annually thereafter. Kaplan–Meier curves and the log-rank test were used to compare the incidence of ILD between RA patients taking different b/tsDMARDs. Hazard ratios (HRs) were calculated by Cox regression analyses. Results: In total, 2492 patients (1967 in the b/tsDMARDs group and 525 in the csDMARDs group) were analyzed. The b/tsDMARDs group showed longer disease duration, higher erythrocyte sedimentation rate/C-reactive protein, and higher disease activity score-28 (DAS28) than the csDMARDs group. The incidence of ILD was significantly higher in those taking tumor necrosis factor inhibitors and abatacept than in those taking csDMARDs (log ranked p &lt; 0.001). Multivariate Cox regression analysis identified older age (HR = 1.057, p = 0.001), male sex (HR = 2.824, p = 0.007), time-averaged DAS28 (HR = 2.241, p &lt; 0.001), and rheumatoid factor titer (HR = 1.009, p = 0.007) as having a significantly increased HR for ILD occurrence. Conclusion: ILD is a rare but critical extra-articular symptom of RA patients. Therefore, RA patients with the above risk factors should be monitored carefully for ILD development.

Complementary Therapies and Their Association with Problems in Therapeutic Adherence to Conventional Synthetic DMARDs in Rheumatoid Arthritis: A Cross-Sectional Study.

The use of complementary therapies is highly prevalent among patients with rheumatoid arthritis (RA). Nevertheless, the use of complementary medicine could involve problems in the following of scientifically accepted treatments. To date, there is limited information regarding the association of nonconventional therapies with problems regarding compliance with the treatment. Therefore, the objective of this study was to identify whether the utilization of complementary therapies is associated with a high risk of problems regarding therapeutic adherence to conventional synthetic disease-modifying anti-rheumatic drugs (cs-DMARDs) in RA patients. A survey was performed with RA patients in an outpatient rheumatology clinic in a university hospital; the use of complementary therapies, as well as their type, was identified. To assess problems with therapeutic adherence, we used the four-item Morisky-Green scale. A comprehensive assessment of clinical and therapeutic characteristics was performed. Univariable and multivariable models were performed to identify the risk of problems with therapeutic adherence in users of complementary therapies. In total, 250 RA patients were included; 92% used complementary therapies. Of them, the most frequently used were herbal medicine (65%), homeopathy (64%), and cannabis and its derivatives (51%). In the univariable logistic regression analysis, the factors associated with problems in the therapeutic adherence to cs-DMARDs were age (p = 0.019), the presence of other comorbidities (p = 0.047), and the use of complementary therapies (p = 0.042). After controlling for potential confounders, the use of complementary therapies increased the risk of problems with therapeutic adherence to cs-DMARDs (adjusted OR = 2.84, 95% CI = 1.06-7.63, p = 0.037). We concluded that the use of complementary therapies increases the risk of problems with therapeutic adherence. Therefore, for physicians and healthcare professionals, the early identification of the use of nonconventional therapies in their RA patients is required, followed by a directed discussion with their patients about the risks and benefits to which they could be exposed to complementary therapies.

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

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

Psoriatic arthritis: the role of self-reported non-adherence, non-trough drug levels, immunogenicity and conventional synthetic DMARD co-therapy in adalimumab and etanercept response.

The aim of this study was to assess the relationship between self-reported non-adherence, non-trough drug levels, immunogenicity and conventional synthetic DMARD (csDMARD) co-therapy in TNF inhibitor (TNF-i) drug response in PsA. Serum samples and adherence questionnaires were collected at baseline, 3, 6 and 12 months for PsA patients prescribed TNF-i. Non-trough adalimumab (ADL) and etanercept (ETN) drug levels were measured at 3 and 6 months using commercially available ELISAs. Clinical response was assessed using PsA response criteria (PsARC) and change in 28-joint DAS (ΔDAS28) between baseline and 3, 6 and 12 months. In 244 PsA patients (52.5% ADL and 47.5% ETN), self-reported non-adherence was associated with PsARC non-response over 12 months using generalized estimating equation (GEE) modelling (P = 0.037). However, there was no significant difference between non-trough ADL or ETN drug levels based on self-reported non-adherence. Higher ETN levels at 3 months were associated with PsARC response at 3 (P = 0.015), 6 (P = 0.037) and 12 months (P = 0.015) and over 12 months using GEE modelling (P = 0.026). Increased ADL drug levels at 3 months were associated with greater ΔDAS28 at 3 months (P = 0.019). ADL anti-drug antibody-positive status was significantly associated with lower 3- and 6-month ADL levels (P < 0.001) and ΔDAS28 and PsARC response at 3, 6 and 12 months. Meanwhile, MTX co-therapy was associated with a reduction in immunogenicity at 3 and 6 months (P = 0.008 and P = 0.024). Although both were associated with reduced response, the objectively measured non-trough drug levels showed more significant associations with drug response than self-reported non-adherence measures.

An international multi-centre analysis of current prescribing practices and shared decision-making in psoriatic arthritis.

Shared decision-making (SDM) is advocated to improve patient outcomes in Psoriatic arthritis (PsA). We analysed current prescribing practices and the extent of SDM in PsA across Europe. The ASSIST study was a cross-sectional observational study of PsA patients aged ≥18 years attending face-to-face appointments between July 2021-March 2022. Patient demographics, current treatment and treatment decisions were recorded. SDM was measured by the clinician's effort to collaborate (CollaboRATE questionnaire) and patient communication confidence (PEPPI-5 tool). 503 patients were included from 24 centres across the UK, France, Germany, Italy and Spain. Physician- and patient-reported measures of disease activity were highest in the UK. Conventional synthetic DMARDs constituted a higher percentage of current PsA treatment in UK than continental Europe (66.4% vs 44.9%), which differed from biologic DMARDs (36.4% vs 64.4%). Implementing treatment escalation was most common in the UK. CollaboRATE and PEPPI-5 scores were high across centres. Of 31 patients with low CollaboRATE scores (<4.5), no patients with low PsAID-12 scores (<5) had treatment escalation. However, of 465 patients with CollaboRATE scores ≥4.5, 59 patients with low PsAID-12 scores received treatment escalation. Higher rates of treatment escalation seen in the UK may be explained by higher disease activity and a younger cohort. High levels of collaboration in face-to-face PsA consultations suggests effective implementation of the SDM approach. Our data indicate that, in patients with mild disease activity, only those with higher perceived collaboration underwent treatment escalation. Prospective studies should examine the impact of SDM on PsA patient outcomes. clinicaltrials.gov, NCT05171270.

Persistence of Janus-kinase (JAK) inhibitors in rheumatoid arthritis: Australia wide study

BackgroundTo compare persistence of disease-modifying antirheumatic (DMARDs), with a focus on Janus kinase (JAK) inhibitors in Australian rheumatoid arthritis (RA) patients. MethodsA retrospective observational study was conducted among 4,521 RA patients (females n=3,181 [70.4%]), using data from the Services Australia 10% Pharmaceuticals Benefits Scheme (PBS) dataset, aged ≥18 years and initiating a DMARD between 2011 to 2021. Kaplan-Meier analysis was used to estimate persistence rates, defined as occurrence of 6 months gap after the end of a drug dispensing. ResultsTwelve-month persistence rates were 72% for upadacitinib, 61% for baricitinib, 58% for subcutaneous tumor necrosis factor-alpha inhibitors (TNFi), 55% for tocilizumab, 53% for tofacitinib, and 49% for abatacept. Median treatment persistence was not reached for upadacitinib (n=574) and baricitinib (n=553); and was 15.0 months for tofacitinib (95% CI 13.5–19.5), 20.5 months for TNFi (95% CI 19.0–22.4), 19.1 months for tocilizumab (95% CI 17.9–23.6), and 12.5 months for abatacept (95% CI 10.4–14.9). Persistence rates on first-line JAK inhibitors were 68% for upadacitinib and baricitinib and 55% for tofacitinib, and 49% for TNFi, 55% for abatacept, and 57% for tocilizumab; rates were sustained for upadacitinib, TNFi, and tocilizumab but dropped to 59% for baricitinib and 47% for abatacept in the second-line treatment. For each b/tsDMARD, persistence rates were higher when combined with methotrexate or other conventional synthetic DMARDs. The median oral glucocorticoid dose decreased from 4.3 mg/day (range:0–40) to 2.3 mg/day (range:0–22) over 2 years. Changes were significant for all RA DMARDs, tofacitinib and baricitinib combined (1–2 years post initiation only), TNFi, abatacept, and tocilizumab. ConclusionsIn a real-world setting, we showed highest persistence rates on upadacitinib, followed by baricitinib and then TNFi therapy and was improved by co-therapy. All agents appeared to be corticosteroid sparing.

Comparative effectiveness of biological disease-modifying antirheumatic drugs and Janus kinase inhibitor monotherapy in rheumatoid arthritis.

To examine the effectiveness and drug tolerability of biological disease-modifying antirheumatic drugs (bDMARDs) and Janus kinase inhibitor (JAKi) monotherapy in patients with rheumatoid arthritis (RA) in a multicentre cohort study. Patients with RA initiated with bDMARD/JAKi monotherapy without conventional synthetic DMARDs were included. Monotherapy regimens were categorised as interleukin-6 receptor inhibitors (IL-6Ri), cytotoxic T-lymphocyte-associated protein 4 immunoglobulin (CTLA4Ig), JAKi, or tumour necrosis factor inhibitors (TNFi). Multiple propensity score-based inverse probability weighting (IPW) was used to reduce selection bias. Linear mixed-effect models with IPW were used to examine changes in the disease activity score in 28 joints (DAS28)-erythrocyte sedimentation rate (ESR) at 24 weeks, and drug retention was compared among monotherapy using IPW Cox proportional hazards models. A total of 849 treatment courses from 635 patients were included (IL-6Ri, 218; CTLA4Ig, 183; JAKi, 92; TNFi, 356). The difference in change in DAS28-ESR at week 24 as the primary outcome was -0.93 (95% CI: -1.20 to -0.66) lower in the IL-6Ri group than TNFi, while that of CTLA4Ig and JAKi was similar with that of TNFi (-0.20 [-0.48 to 0.08], -0.25 [-0.67 to 0.16], respectively). IL-6Ri use was associated with significantly lower overall drug discontinuation than TNFi use (hazard ratio = 0.55 [0.39-0.78], P = 0.001). Similar retention rates were identified among CTLA4Ig and JAKi compared to TNFi. In the analysis with IPW to reduce selection bias, IL-6Ri monotherapy was superior to TNFi monotherapy in terms of effectiveness and drug retention. No significant differences were identified between CTLA4Ig, JAKi, and TNFi monotherapy.

Relapse after cessation of weekly tocilizumab for giant cell arteritis: a multicentre service evaluation in England.

The National Health Service in England funds 12 months of weekly subcutaneous tocilizumab (qwTCZ) for patients with relapsing or refractory giant cell arteritis (GCA). During the COVID-19 pandemic, some patients were allowed longer treatment. We sought to describe what happened to patients after cessation of qwTCZ. Multicentre service evaluation of relapse after stopping qwTCZ for GCA. The log-rank test was used to identify significant differences in time to relapse. 336 GCA patients were analysed from 40 centres, treated with qwTCZ for a median (interquartile range, IQR) of 12 (12-17) months. At time of stopping qwTCZ, median (IQR) prednisolone dose was 2 (0-5) mg/day. By 6, 12 and 24 months after stopping qwTCZ, 21.4%, 35.4% and 48.6% respectively had relapsed, requiring an increase in prednisolone dose to a median (IQR) of 20 (10-40) mg/day. 33.6% of relapsers had a major relapse as defined by EULAR. Time to relapse was shorter in those that had previously also relapsed during qwTCZ treatment (P = 0.0017); in those not in remission at qwTCZ cessation (P = 0.0036); and in those with large vessel involvement on imaging (P = 0.0296). Age ≥65, gender, GCA-related sight loss, qwTCZ treatment duration, TCZ taper, prednisolone dosing, and conventional synthetic DMARD use were not associated with time to relapse. Up to half our patients with GCA relapsed after stopping qwTCZ, often requiring a substantial increase in prednisolone dose. One third of relapsers had a major relapse. Extended use of TCZ or repeat treatment for relapse should be considered for these patients.

Factors associated of long-term retention rate of Janus kinase inhibitors in a multi-failure rheumatoid arthritis population.

We aimed to retrospectively evaluate retention rate and causes of discontinuation of JAKi in RA patients with particular regards to difficult-to-treat subgroups. The diffusion of Janus kinase inhibitors (JAKi) for the treatment of rheumatoid arthritis (RA) has rapidly increased in recent years due to their effectiveness, even in difficult-to-treat subgroups of patients. After the publication of the Oral Surveillance study, the labelling of JAKi was modified, advising against their use in elderly patients and those at risk for cardiovascular events and malignancies. Demographic, clinical, serological and therapeutic characteristics of RA patients treated with JAKi were recorded, including smoking habit and comorbidities. Three hundred and thirty consecutive RA patients were enrolled in the study. Among them, 50.3% patients had previously failed at least two biologic DMARDs. Risk factors for the use of JAKi were reported in 75.5% of patients, 41.5% of them were older than 65 years, 37.6% had smoked, while 48.8% had increased cardiovascular or cancer risk. Anticitrullinated peptide antibodies (ACPA) and combination therapy with conventional synthetic DMARDs were associated with a longer drug persistence and ACPA remained independently associated to a higher retention rate of JAKi also in the subgroup of difficult-to-treat patients. In conclusion, our study supports the clinical effectiveness of JAKi in RA, even in the multi-failure subgroup of patients, where the risk/benefit ratio overcomes the safety risk. The presence of ACPA and the concurrent use of + cs-DMARD may increase the survival on JAKi in the long term.