Use Of Synthetic Disease-modifying Anti-rheumatic Drugs Research Articles

Treat-to-target vs fixed interval retreatment strategy with rituximab in rheumatoid arthritis: a retrospective cohort study.

To compare the effectiveness of retreatment of rheumatoid arthritis (RA) patients with rituximab (RTX) following the treat-to-target retreatment (TTr) or fixed interval retreatment (FIr) strategy. RA patients starting RTX treatment between January 2008 and June 2016, and receiving at least three infusion cycles were grouped by strategy (TTr, FIr or both). Primary outcome (between strategy difference in DAS28-CRP (Disease Activity Score in 28 joints calculated with C-reactive protein)) and secondary outcomes (flares, use of co-medication and mean yearly dose of RTX) were analyzed by group using linear mixed models to account for different strategies within patients. A total of 213 patients, 59 TTr (of whom 32 switched from TTr to FIr) and 186 FIr were included. No between-group difference in mean DAS28-CRP was found (0.10 DAS28-CRP point (95% CI -0.07 to 0.26)). The TTr strategy did not result in more flares (IRR 1.13, 95%CI 0.87 to 1.47), conventional synthetic disease-modifying antirheumatic drug use (difference -11.7%, 95%CI -26.3% to 2.9%), or lower mean yearly RTX dose (difference 172mg/yr, 95%CI -355 to 11.7 mg/yr). RTX retreatment with either a TTr or FIr strategy does not seem to lead to better disease control and/or less drug use when used in a DAS28-CRP treat-to-target context. Choice of either strategy can, therefore, be made based on patient and physician preferences and logistical context.

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

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

The impact of smoking on response to tumor necrosis factor-α inhibitor treatment in patients with ankylosing spondylitis.

To investigate the impact of smoking on disease activity, treatment retention, and response in patients with ankylosing spondylitis (AS) treated with their first tumor necrosis factor-α inhibitor (TNFi). AS patients who started their first TNFi treatment for the active axial disease (BASDAI ≥ 4) from TURKBIO Registry were included. Treatment response of smoker (current and ex-smokers) and nonsmoker (never smoker) patients were primarily evaluated as achievement of BASDAI50 or improvement in BASDAI at least 20 mm at 3 months and 6 months compared to baseline. There were 322 patients with AS (60% male, 59% smoker, mean age: 38.3 years). The median follow-up time was 2.8 years (Q1- Q3: 1.3-3.8), and disease duration was 3.5 years (Q1-Q3: 0.7-8.2). Smokers had male predominance (p < 0.001), lower ESR (p = 0.03), higher BASDAI (p = 0.02), BASFI (p = 0.05), HAQ-AS (p = 0.007), and ASDAS-CRP (p = 0.04) compared with nonsmokers at baseline. In the multivariate analysis, male gender [OR 2.7 (95%CI 1.4-5), p = 0.002], and concomitant conventional synthetic disease-modifying antirheumatic drug use [OR 2.4 (95%CI 1.1-5.2), p = 0.03] were associated with better treatment response. There was an association of male gender [HR 2.4 (95%CI 1.6-3.7), p < 0.001], older age (≥30years) [HR 1.8 (95%CI 1.1-2.8), p = 0.01], and response to treatment [HR 1.8 (95%CI 1.2-2.9), p = 0.008] with better treatment retention. No impact of smoking status was found on treatment retention and response in univariate and multivariate analyses. This study suggested that smoking was associated with poorer patient-reported outcomes in biologic naïve AS patients initiating their first TNFi treatment, but it had no impact on the TNFi treatment response and retention rate.

Sex and gender impact on achievement of remission in people with rheumatoid arthritis in Switzerland: a cohort study

<h2>Abstract</h2><h3>Background</h3> Sex and gender can play a role in rheumatoid arthritis; thus, we aimed to compare the likelihood of reaching remission in men and women with rheumatoid arthritis. <h3>Methods</h3> This observational cohort study was done using the Swiss Clinical Quality Management in Rheumatic Diseases (SCQM) registry (1997–2019). The study included adults (older than 18 years) with rheumatoid arthritis who started their first biologic or targeted synthetic disease-modifying antirheumatic drug (DMARD) before April 30, 2018. Those without a recorded baseline visit were excluded. The study exposure was sex (biological) and gender (social construct). Exposure data were recorded as male and female but referred to here as men and women. Patient baseline characteristics were compared between men and women. Logistic regression was used to compare the odds of reaching remission at 12 months or less (defined by the Disease Activity Score 28-joints [DAS28] of <2·6) in men versus women. We also investigated potential mediators (baseline DAS28 [≥3·2 <i>vs</i> <3·2], disease duration [>2 <i>vs</i> ≤2 years], elevated BMI [≥25 <i>vs</i> BMI <25], conventional synthetic DMARD use at index date [yes <i>vs</i> no], and steroid use at index date [yes <i>vs</i> no]) using logistic regression. <h3>Findings</h3> We included 3722 patients with rheumatoid arthritis who were new users of biologic or targeted synthetic DMARDs. 2839 (76·3%) patients were women and 883 (23·7%) were men. The median age was 56·8 years (IQR 46·9–65·2). Men were older at diagnosis and at the start of treatment and had a shorter time from diagnosis to starting their first biologic or targeted synthetic DMARD (3·43 years [IQR 1·15–9·93] <i>vs</i> 4·95 years [1·68–12·03] in women; p<0·0001). At baseline, women had significantly higher disease activity (DAS28 4·40 [SD 1·36] <i>vs</i> 4·17 [1·52] in men; p=0·0001) and worse Health Assessment Questionnaire scores (1·00 [IQR 0·50–1·62] <i>vs</i> 0·88 [0·38–1·38] in men; p<0·0001) and tender joints (5·00 [IQR 2·00–11·00] <i>vs</i> 4·00 [1·00–10·00] in men; p=0·020). Compared with women, men were more likely to reach DAS28 remission at 12 months or less (odds ratio [OR] 1·21, 95% CI 1·02–1·42; p=0·026). Adjusting for age and seropositivity resulted in similar findings (adjusted OR 1·24, 1·05–1·46; p=0·012). Mediation analyses showed lower odds of baseline DAS28 at 3·2 or higher (OR 0·65, 0·53–0·78; p<0·0001) and disease duration of more than 2 years (OR 0·71, 0·60–0·83; p<0·0001) in men compared with women. Further mediation analyses identified baseline DAS28 and disease duration as factors that might explain the association between sex, gender, and DAS28 remission. <h3>Interpretation</h3> Among patients with rheumatoid arthritis who received biologic or targeted synthetic DMARDs, men with rheumatoid arthritis had higher odds of reaching remission than women, which could be explained by the earlier escalation to treatment with biologic or targeted synthetic DMARDs in men versus women. This finding suggests the possibility that starting treatment at earlier stage of disease in women may be beneficial and reduce the observed disparity. <h3>Funding</h3> None.

Sustained and improved guselkumab response in patients with active psoriatic arthritis regardless of baseline demographic and disease characteristics: pooled results through week 52 of two phase III, randomised, placebo-controlled studies

ObjectivesTo evaluate the efficacy through 52 weeks of guselkumab, an interleukin 23-p19 subunit inhibitor, in subgroups of pooled psoriatic arthritis (PsA) patients from the DISCOVER-1 and DISCOVER-2 trials defined by...

Provider Specialty and the Use of Disease‐Modifying Antirheumatic Drugs for Rheumatoid Arthritis Among Older Adults in the 2005‐2016 National Ambulatory Medical Care Survey

ObjectiveWe compared disease‐modifying antirheumatic drug (DMARD) use for older adults with rheumatoid arthritis (RA)‐related ambulatory visits from rheumatologists and primary care providers (PCPs).MethodsIn this study of national sample office visits, we characterized ambulatory visits by older adults 65 years of age or older seen by rheumatologists or PCPs for diagnosis of RA using the 2005‐2016 National Ambulatory Medical Care Survey. We analyzed patterns and trends of DMARD use using descriptive statistics and multivariable analyses by provider specialty.ResultsWe identified 518 observations representing 7,873,246 ambulatory RA visits by older adults over 12 years; 74% were with rheumatologists. Any DMARD use was recorded at 56% of rheumatologist and 30% of PCP visits. Among visits with any DMARD use, 20% of rheumatologist visits had two or more DMARDs compared with 6% of PCP visits. Over the 12‐year study period, there was no statistical difference in trend of any or conventional synthetic DMARD use at visits by provider specialty, adjusted for patient characteristics, non‐DMARD polypharmacy and multimorbidity. However, biologic DMARD use was more likely to incrementally increase with rheumatologist compared with PCP visits (P = 0.003).ConclusionDMARD use for older adults with RA remains low from both rheumatologists and PCPs, including biologic DMARDs, even though American College of Rheumatology guidelines recommend earlier and more aggressive treatment of RA. With predicted shortages in the rheumatology workforce and maldistribution of rheumatology providers, PCPs may play an increasingly important role in caring for older adults with RA. Further research is needed to understand to optimize appropriate use of DMARDs in older patients with RA.

Multicenter, Open-Label, Long-term Extension to Describe the Safety of Tocilizumab in Patients with Early, Moderate to Severe Rheumatoid Arthritis

Introduction: Biologic DMARDs (Disease Modifying Anti Rheumatic Drugs) have shown to be effective in the treatment of rheumatoid arthritis (RA) resistant to the use of synthetic DMARDs. The primary goal of this study was to assess the long-term safety of the use of tocilizumab in patients with early rheumatoid arthritis, moderate to severe disease activity. The secondary goal was to assess the efficiency of tocilizumab in achieving and maintaining clinical remission of the disease. Methods: ML28133 is a long-term, extended study of 13 patients with rheumatoid arthritis treated with tocilizumab. Two patients were male (15.4%), 11 (84.61%) female. The average age of patients was 53.27+/-10.68. Patients received 8 mg/kg tocilizumab i.v. every four weeks, 104 weeks overall. Safety was assessed following side effects, blood tests, physical examination and vital signs. Efficiency was assessed by achieving and maintaining clinical remission according to DAS28 (Disease Activity Score 28), global assessment of disease activity, VAS score and HAQ-DI (Health Activity Score) questionnaire. Results: Incidence of side effects was 76.92%. Infections were of special interest and were most common (15.3%). Four patients had serious adverse events, three of which associated with tocilizumab, and therapy was stopped. In 11 (84.6%) of the 13 treated patients clinical remission was achieved at times. At the end of the study, 8 out of 9 patients were in remission. Conclusion: The results have shown significant therapeutic effect of tocilizumab even in the most severe forms of the disease, which gives hope for its use as a monotherapy.

Multicenter, Open-Label, Long-term Extension to Describe the Safety of Tocilizumab in Patients with Early, Moderate to Severe Rheumatoid Arthritis

Introduction: Biologic DMARDs (Disease Modifying Anti Rheumatic Drugs) have shown to be effective in the treatment of rheumatoid arthritis (RA) resistant to the use of synthetic DMARDs. The primary goal of this study was to assess the long-term safety of the use of tocilizumab in patients with early rheumatoid arthritis, moderate to severe disease activity. The secondary goal was to assess the efficiency of tocilizumab in achieving and maintaining clinical remission of the disease. Methods: ML28133 is a long-term, extended study of 13 patients with rheumatoid arthritis treated with tocilizumab. Two patients were male (15.4%), 11 (84.61%) female. The average age of patients was 53.27+/-10.68. Patients received 8 mg/kg tocilizumab i.v. every four weeks, 104 weeks overall. Safety was assessed following side effects, blood tests, physical examination and vital signs. Efficiency was assessed by achieving and maintaining clinical remission according to DAS28 (Disease Activity Score 28), global assessment of disease activity, VAS score and HAQ-DI (Health Activity Score) questionnaire. Results: Incidence of side effects was 76.92%. Infections were of special interest and were most common (15.3%). Four patients had serious adverse events, three of which associated with tocilizumab, and therapy was stopped. In 11 (84.6%) of the 13 treated patients clinical remission was achieved at times. At the end of the study, 8 out of 9 patients were in remission. Conclusion: The results have shown significant therapeutic effect of tocilizumab even in the most severe forms of the disease, which gives hope for its use as a monotherapy.

Sarcopenia-associated factors in Japanese patients with rheumatoid arthritis: A cross-sectional study.

To evaluate the prevalence rate and factors associated with sarcopenia in Japanese patients with rheumatoid arthritis. We enrolled 240 consecutive patients with rheumatoid arthritis aged ≥65 years in this study. We examined clinical data: age, sex, body mass index, disease duration, rheumatoid factor positivity, anti-cyclic citrullinated peptide antibody positivity, biological or target synthetic disease-modifying antirheumatic drug use, methotrexate use, glucocorticoid use, C-reactive protein level, disease activity score in 28 joints-erythrocyte sedimentation rate, Health Assessment Questionnaire Disability Index, bone mineral density of the lumbar spine and total hip, grip strength, gait speed, and relative skeletal muscle mass index by bioelectrical impedance analysis. Sarcopenia was defined according to a consensus report by the Asian Working Group for Sarcopenia. The prevalence rate of sarcopenia was found to be 29.6%. Multivariate analysis identified the following factors to be associated with sarcopenia: age (P = 0.008; odds ratio 1.08), body mass index (P < 0.001; odds ratio 0.73), C-reactive protein (P = 0.017; odds ratio 1.76) and hip bone mineral density (P = 0.037; odds ratio 0.61). The sarcopenia-associated factors were age, body mass index, C-reactive protein and hip bone mineral density in Japanese patients with rheumatoid arthritis. Because the Health Assessment Questionnaire Disability Index, a standard measurement of function, cannot predict sarcopenia, the muscle mass needs to be measured while assessing changes in grip strength, body mass index, C-reactive protein and hip bone mineral density. Geriatr Gerontol Int 2019; 19: 907-912.

Conventional synthetic disease-modifying antirheumatic drug use by race/ethnicity and factors associated with initiating biologics in Malaysian patients with rheumatoid arthritis

Aims: The aim of the study was to evaluate the treatment patterns of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), drug survival, and the factors in initiating biologic DMARDs based on race and ethnicity in rheumatoid arthritis (RA) patients. Materials and Methods: Data on RA patients, including race/ethnicity, who were attending University Malaya Medical Centre, Kuala Lumpur, Malaysia, and started on csDMARDs between January 2006 and December 2016, were collected retrospectively from the review of patients' medical records. Factors in initiating biologic DMARDs were identified. Results: A total of 369 RA patients received at least one csDMARD; 325 (88.1%) were female, and 271 (73.4%) were seropositive. Three main races were identified: Malay (28.7%), Chinese (33.1%), Indian (36.3%), and others (1.9%). Malay race patients were initiated on a csDMARD at a younger age (48.6 years, standard deviation [SD]: 12.4) due to younger age at onset compared to other races (P Conclusion: CsDMARDs in RA were required at a younger age for a certain race due to younger age at onset. However, race does not predict the initiation of biologics and no significant difference in the use of combination csDMARDs between races.

Ml28133 -A Multicenter, Open-Label, Long-Term Extension Study of WA 19926 to Describe Safety During Treatment with Tocilizumab in Patients with Early, Moderate to Severe Rheumatoid Arthritis

Abstract Introduction. Biologic DMARDs (Disease Modifying Anti Rheumatic Drugs) have shown to be effective in the treatment of rheumatoid arthritis (RA) resistant to the use of synthetic DMARDs. The primary goal of this study wasto assess the long-term safety of the use of tocilizumab in patients with early rheumatoid arthritis, moderate to severe disease activity. The secondary goal was to assess the efficiency of tocilizumab in achieving and maintaining clinical remission of the disease. Methods. ML28133 is a long-term, extended study of 13 patients with rheumatoid arthritis treated with tocilizumab. Two patients were male (15.4%), 11(84.61%) female. The average age of patients was 53.27+/−10.68. Patients received 8mg/kg tocilizumab i.v. every four weeks, 104 weeks overall. Safety was assessed following side effects, blood tests, physical examination and vital signs. Efficiency was assessed by achieving and maintaining clinical remission according to DAS28 (Disease Activity Score 28), global assessment of disease activity, VAS score and HAQ-DI (Health Activity Score) questionnaire. Results. Incidence of side effects was 76.92%. Infections were of special interest and were most common (15.3%). Four patients had serious adverse events, three of which associated with tocilizumab, and therapy was stopped. In 11 (84.6%) of the 13 treated patients clinical remission was achieved at times. At the end of the study, 8 out of 9 patients were in remission. Conclusion. The results have shown significant therapeutic effect of tocilizumab even in the most severe forms of the disease, which gives hope for its use as a monotherapy.

Specific therapy to regulate inflammation in rheumatoid arthritis: molecular aspects.

Rheumatoid arthritis (RA) is a chronic inflammatory disease in which persistent inflammation of synovial tissue results in a progressive functional decline of the joint and premature mortality. TNF inhibitors were the first biological disease-modifying antirheumatic drugs (DMARDs) used to treat RA. Since then, new biological drugs have emerged, such as inhibitors of IL-1, IL-6 and others, with different mechanisms of action that include the depletion of B cells and the inhibition of T-cell costimulation. Recently, RA treatments have incorporated the use of synthetic DMARDs. This review describes the molecular aspects of the mechanisms of action of biological and synthetic DMARDs, discusses the adverse effects and limitations of established therapies and analyses the alternative approaches to RA treatment.

Use of Synthetic and Biological DMARDs in Treatment of Ankylosing Spondylitis at a University Hospital

Aim: Sulphasalazine is used widely as a second-line treatment of ankylosing spondylitis (AS) after non-steroidal anti-inflammatory drugs (NSAIDs) in Finland. The objective of this study is to evaluate the use of disease-modifying anti-rheumatic drugs (DMARDs) and drug survival in incident AS patients at Helsinki University Central Hospital (HUCH). Method: We identified all incident patients with AS in the hospital register from 1 Jan 2005 to 31 Dec 2009. The index day was defined as the date of AS diagnosis. Medication and clinical data were evaluated until the end of 2010. Results: 176 patients were identified. For 165 of them a DMARD was started. In 9 patients with low disease activity the drug treatment consisted only of NSAIDs. Sulphasalazine was the first synthetic DMARD for 157 (95%) patients. No one were prescribed a biologic drug as the first DMARD. The mean follow-up time was 3.8 years. The mean synthetic DMARD survival was 80%. Bath AS Disease Activity Index (BASDAI) available from 46 patients was 4.1 (1.8) at baseline and decreased by 1.6 (95% CI 2.2-1.1, p<0.001) during the DMARD treatment. Because of continuing disease activity, 28 (17%) patients became eligible for reimbursement of biological DMARDs and a TNF inhibitor was instituted. This was predicted by peripheral disease, higher ESR, and CRP at the baseline. Conclusion: Most patients with incident AS do fairly well with synthetic DMARDs but the proportion of the patients needing biological DMARD treatment grows over time. Use of synthetic DMARDs may reduce or postpone the need for biological DMARD treatment in AS.