Current Disease-modifying Antirheumatic Drugs Research Articles

P143 High throughput multiplex assay identifies clinically meaningful clusters in systemic sclerosis patients with low cardiovascular risk and no history of heart disease

Abstract Background/Aims People with systemic sclerosis (SSc) often show subclinical evidence of primary heart involvement (pHI), which when clinically evident, is a prognostic factor of poor outcome. We aimed to profile serum proteins in patients with SSc and no history of pHI and identify clinically meaningful clusters to aid early identification and stratification for pHI. Methods Serum from 78 patients from CONVAS (‘CONnective Tissue Disease and VASculitis Cohort’) and ELCASA (‘ELectrophysiology and CArdiac imaging in SclerodermA’) cohorts [no history of pHI, pulmonary hypertension, diabetes or > 2 traditional cardiovascular (CV) risk factors] was used to measure 355 proteins across inflammation, cardiometabolic and cardiovascular II/III Olink panels. Unsupervised hierarchical clustering using scaled normalised protein expression (NPX) was used to define clusters. Demographic and clinical characteristics were compared between clusters and significant differences reported using Kruskal-Wallis rank sum test for continuous or Pearson’s chi-squared test for categorical variables, at the 5% significance threshold. Results Clinical characteristics of the patient cohorts have been previously published (also summarised in table 1,column 2). Unsupervised hierarchical clustering revealed three patient clusters - C1 [27/78 (35%)], C2 [33/78 (42%)] and C3 [18/78 (23%)] with intermediate, low and high protein expression respectively. C2 patients were younger (median age 51 years) compared to C1 (61 years) and C3 (58 years) (p < 0.001). High expression cluster C3 had a significantly higher proportion of males [7/18 (39%)](p = 0.009), shorter disease duration [median 1.15 years, IQR (0.66 to 7.23)], higher modified Rodnan skin scores (MRSS) [median 5.50, IQR (3.25 to 11)] (p = 0.002) and current disease modifying anti-rheumatic drugs (DMARD) use [16/18 (89%)](p = 0.005). NTproBNP and CRP were elevated in C1 and C3, and high-sensitivity troponin I (hsTnI) was highest in C3[median 6.15 IQR (5.08 to 89.58)](p = 0.002); n = 3 within C1 showed especially high NTproBNP (median 227.50pg/ml) and CRP (median 13mg/dl). No differences in antibody profiles were noted across the three clusters (table 1). Conclusion Differences in serum protein expression identifies clinically meaningful clusters of SSc patients with elevated acute phase and serum cardiac markers despite low CV risk profile. Future work should assess their utility as prognostic biomarkers of SSc-pHI. Disclosure R. Shukla: None. R. Dumitru: Grants/research support; ACORN charity and Charitable Foundation Fellowship, Leeds Teaching Hospital. B. Erhayiem: None. G. Fent: None. F. Del Galdo: Consultancies; Abbvie, AstraZeneca, Boehringer-Ingelheim, Capella, Chemomab, GSK, Janssen, Mitsubishi-Tanabe. S. Plein: Other; funded by a British Heart Foundation Personal Chair. D. Plant: None. M.H. Buch: Consultancies; AbbVie, Arxx Therapeutics, Boehringer Ingelheim, Galapagos, Gilead, and Pfizer (all paid to host institution).

Patient satisfaction with medication in rheumatoid arthritis: an unmet need.

Shared decision-making between rheumatologists and patients has become an overarching principle in current treatment recommendations in rheumatoid arthritis (RA). Therefore, in the present study, we aimed to assess the satisfaction of patients with RA with their treatment and to investigate the associated factors. A cross-sectional study was carried out in the Rheumatology Department of Mongi Slim Hospital. We included adults with RA receiving their current disease-modifying anti-rheumatic drugs for at least 12 months.Satisfaction among patients was assessed by the Treatment Satisfaction Questionnaire for Medication (TSQM) and it was defined by a score ≥ 80%. The factors indirectly influencing patient satisfaction that were assessed were: satisfaction with medical care management, disease activity, functional impact, professional impact, and the impact of RA. Multivariable regression analysis was applied to determine the predictors of satisfaction. We included 70 patients (63 female/7 male) with a mean age of 57.8 ±10.6 years. The mean disease duration was 13.71 ±7.2 years.Mean TSQM scores were 65.42 ±14.77 for convenience, 68.71 ±18 for effectiveness, 70.60 ±24.5 for side effects, and 67.95 ±17.10 for global satisfaction. Satisfaction rates were: 20% for convenience, 39% for effectiveness, 46% for side effects and 30% for global satisfaction.In multivariable analysis, the predictors of global dissatisfaction were Rheumatoid Arthritis Impact of Disease (RAID) overall score (p = 0.003) and the degree of physical difficulties (p = 0.001). Satisfaction with the physician was correlated with better global satisfaction (p = 0.029). Difficulties in adapting to RA (p = 0.043) and current treatment with biologics (p = 0.027) were predictors of dissatisfaction with convenience. Predictors of dissatisfaction with efficiency were the RAID overall score (p = 0.032) and the difficulties of adapting to RA (p = 0.013). The predictors of satisfaction with side effects were a lower degree of interference with domestic work (p = 0.02) and better involvement of the patient in the treatment decision (p = 0.014). The satisfaction with the attending physician, the participation in the treatment decision, and the impact of RA seem to influence treatment satisfaction the most. These data suggest that a better understanding of patients' medical needs and preferences would improve satisfaction outcomes.

Patient satisfaction, preferences, expectations, characteristics, and impact of suboptimal control of rheumatoid arthritis: A subgroup analysis of Japanese patients from a large international cohort study (SENSE).

ObjectiveTo evaluate treatment satisfaction, disease outcomes, and perspectives of patients with poorly controlled rheumatoid arthritis (RA) treated with conventional synthetic, targeted synthetic, or biologic disease-modifying antirheumatic drugs (DMARDs), we conducted a subgroup (post hoc) analysis of Japanese patients participating in the SENSE study.MethodsData for Japanese patients (n/N = 118/1629) from the global, multicenter, cross-sectional, observational SENSE study were analyzed. The primary endpoint was the global satisfaction subscore assessed using the Treatment Satisfaction Questionnaire for Medication (TSQM) version 1.4. Other patient-reported outcomes included self-reported RA medication adherence and Work Productivity and Activity Impairment-RA. Patient perspectives included patients’ expectations and preference of pharmacologic treatment.ResultsMedian (range) age and RA disease duration were 67.0 (18.0–87.0) years and 8 (0.0-54) years, respectively; 81.4% of patients were female. Mean (SD) TSQM global satisfaction subscore was 56.8 (17.5), and only 5.9% of patients reported good satisfaction with treatment (TSQM global ≥80). Mean (SD) self-reported treatment adherence using VAS was high (93.5% [13.8%]). Mean (SD) total work productivity impairment was 45.6% (32.0%); presenteeism contributed toward more total work productivity impairment (43.9% [30.4%]) than absenteeism (8.3% [24.4%]). Patients expected improvement in all parameters from their treatment, especially improvement in joint symptoms. Most patients (80.7%) preferred oral medication and 18.7% preferred monotherapy. Patient acceptability of potentially manageable side effects was high (7.5%-34.0%). Although most patients (81.3%) found combination therapy acceptable, 43.2% were receiving DMARD monotherapy.ConclusionAlthough most Japanese patients with RA with moderate-to-high disease activity were dissatisfied with their current DMARD treatment, high treatment adherence, high acceptability of combination therapy, high acceptability of manageable potential side effects, and preference for oral medication were reported. Data support the development of a more individualized and patient-centric approach for RA treatment.

P174 Upadacitinib response rates in patients with psoriatic arthritis enrolled in the SELECT-PsA-1 and SELECT-PsA-2 trials assessed according to modified PsARC

P174 Upadacitinib response rates in patients with psoriatic arthritis enrolled in the SELECT-PsA-1 and SELECT-PsA-2 trials assessed according to modified PsARC

Patient Perceptions of Unmet Medical Need in Rheumatoid Arthritis: A Cross-Sectional Survey in the USA.

IntroductionMany rheumatoid arthritis (RA) patients do not achieve their treatment goals and experience symptoms that affect psychosocial outcomes and daily activities. This study aimed to identify and quantify the unmet needs perceived by US patients with RA currently taking a disease-modifying antirheumatic drug (DMARD).MethodsA cross-sectional, web-based survey was conducted with RA patients recruited through CreakyJoints, an online patient support community, and ArthritisPower®, an online patient research registry, from December 2017 to January 2018. Participant patients were aged ≥ 21 years, failed ≥ 1 DMARDs, and were receiving their current DMARD(s) for ≥ 6 months; they answered 50 questions about treatment history, RA symptoms, and flares and completed the Rheumatoid Arthritis Impact of Disease (RAID) questionnaire and the Treatment Satisfaction Questionnaire for Medication (TSQM). Treatment satisfaction was defined by a TSQM global satisfaction score ≥ 80.ResultsOf 415 patients screened, 258 (62%) were eligible and completed the survey; 87% were women, and 87% white, with mean (SD) age of 54.5 (11.4) years. A total of 232 patients (90%) had current or past biologic DMARD (bDMARD) use, with 67% currently on a bDMARD, 65% on ≥ 1 conventional synthetic DMARD, and 40% on methotrexate. Forty-three percent of patients reported daily/almost daily use of prescription pain medications, and 44% reported a current flare. Mean (SD) TSQM scores were 59 [20] for effectiveness, 59 [26] for side effects, 72 [18] for convenience, and 65 [21] for global satisfaction. The mean (SD) RAID overall score was 5.1 (2.0) on a 0–10 scale. Only 26% (67 patients) were satisfied with their RA treatment. Patients not satisfied with treatment reported higher RAID scores overall and by domain, and approximately half reported a current flare.ConclusionsResults from this real-world survey suggest that three-fourths of RA patients are not satisfied with treatments, which include bDMARDs. Patients continued to experience bothersome symptoms that impacted their daily activities and life. There remains a need for improved disease management among currently treated RA patients.FundingEli Lilly and Company (Indianapolis, IN, USA).Electronic Supplementary MaterialThe online version of this article (10.1007/s40744-019-00168-5) contains supplementary material, which is available to authorized users.

Impact of gender on the response and tolerance to abatacept in patients with rheumatoid arthritis: results from the ‘ORA’ registry

ObjectiveThe impact of gender on the response and tolerance to abatacept was assessed in a large prospective cohort during 2 years of follow-up.MethodsFrom the 1017 patients included in the Orencia...

Effect of Atorvastatin on the Disease Activity and Severity of Rheumatoid Arthritis: Double-Blind Randomized Controlled Trial.

HMG-CoA (3-hydroxy-3- methylglutary lcoenzyme A) reductase inhibitors (statins) have anti-inflammatory properties which may be particularly useful in rheumatoid arthritis to suppress disease activity and inflammatory factors. The purpose of this clinical trial was to determine anti-inflammatory properties of statins in rheumatoid arthritis. Eighty Iranian patients with rheumatoid arthritis, aged between 19 to 75 years were recruited to take part in this randomized, double-blind placebo-controlled trial. Subjects were randomly allocated to two groups to take atorvastatin or placebo 40 mg daily as an adjunct to current disease-modifying anti-rheumatic drugs (DMARDs) treatment. Disease Activity Score-28 (DAS28), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), swollen joint count (SJC) & tender joint count (TJC) were assessed before and after three months intervention. Analysis was based on intention to treat. DAS28 significantly declined in the atorvastatin group in comparison with placebo (p< 0.001). SJC, TJC, CRP and ESR also were significantly dropped in the atorvastatin group in comparison with placebo. It can be concluded that atorvastatin can suppress RA activity and inflmmatory factors in RA patients for high to moderate grade of inflmmation.

Disease-modifying Antirheumatic Drugs for the Treatment of Low Back Pain: A Systematic Review of the Literature.

Low back pain (LBP) is a common source of pain and disability, which has an enormous adverse impact on affected individuals and the community as a whole. The etiologies of LBP are protean and local inflammation contributes to the majority of these processes. Although an array of potent disease-modifying anti-rheumatic drugs (DMARDs), which are typically anti-inflammatory in character, have become clinically available only corticosteroids are routinely used for the treatment of LBP. To further investigate this potentially underutilized therapy, we reviewed the available literature to determine the role of DMARDs in the treatment of LBP. Our results show that the current DMARD use for LBP is indeed limited in scope and is characterized by isolated use and empiric selection of drugs from a range of available DMARDs. Moreover, the dose, frequency, and route of drug administration are selected arbitrarily and deviated from treatment protocols proposed for the management of other inflammatory conditions. The literature published on this topic is of low quality, and the results of the reviewed trials were inconclusive or demonstrated only short-term efficacy of these medications. Based on the findings of this review, we recommend that the future DMARD use for LBP is initially limited to patients with debilitating disease who are unresponsive to conventional treatments, and the criteria for drug selection and routes of drug administration are clearly defined and may be modeled after treatment protocols for other inflammatory conditions.

Dendritic cells and the promise of antigen-specific therapy in rheumatoid arthritis

Rheumatoid arthritis (RA) is a systemic inflammatory disease resulting from an autoimmune response to self-antigens, leading to inflammation of synovial tissue of joints and subsequent cartilage and bone erosion. Current disease-modifying anti-rheumatic drugs and biologic inhibitors of TNF, IL-6, T cells and B cells block inflammation nonspecifically, which may lead to adverse effects, including infection. They do not generally induce long-term drug-free remission or restoration of immune tolerance to self-antigens, and lifelong treatment is usual. The development of antigen-specific strategies in RA has so far been limited by insufficient knowledge of autoantigens, of the autoimmune pathogenesis of RA and of the mechanisms of immune tolerance in man. Effective tolerance-inducing antigen-specific immunotherapeutic strategies hold promise of greater specificity, of lower toxicity and of a longer-term solution for controlling or even preventing RA. This paper reviews current understanding of autoantigens and their relationship to immunopathogenesis of RA, and emerging therapeutics that aim to leverage normal tolerance mechanisms for implementation of antigen-specific therapy in RA.

Regional and temporal variation in the treatment of rheumatoid arthritis across the UK: a descriptive register-based cohort study

ObjectivesTo describe current disease-modifying antirheumatic drugs (DMARDs) prescription in rheumatoid arthritis (RA) with reference to best practice and to identify temporal and regional trends in the UK.DesignDescriptive, register-based cohort study.ParticipantsPermanently...

Rheumatoid arthritis patients and rheumatologists approach the decision to escalate care differently: Results of a maximum difference scaling experiment

Antirheumatic treatment is frequently not appropriately modified, according to American College of Rheumatology guidelines, in patients with active rheumatoid arthritis (RA) as defined by a Disease Activity Score in 28 joints (DAS28) score greater than 3.2. The objective of this study was to determine which factors most strongly influence patients' and rheumatologists' decisions to escalate care. We administered a Maximum Difference Scaling survey to 106 rheumatologists and 213 patients with RA. The survey included 58 factors related to the decision to escalate care in RA. Participants answered 24 choice tasks. In each task, participants were asked to choose the most important factor from a set of 5. We used hierarchical Bayes modeling to generate the mean relative importance score (RIS) for each factor. For rheumatologists, the 5 most influential factors were number of swollen joints (mean ± SD RIS 5.2 ± 0.4), DAS28 score (mean ± SD RIS 5.2 ± 0.5), physician global assessment of disease activity (mean ± SD RIS 5.2 ± 0.6), worsening erosions over the last year (mean ± SD RIS 5.2 ± 0.5), and RA disease activity now compared to 3 months ago (mean ± SD RIS 5.1 ± 0.6). For patients, the 5 most important factors were current level of physical functioning (mean ± SD RIS 4.3 ± 1.1), motivation to get better (mean ± SD RIS 3.5 ± 1.4), trust in their rheumatologist (mean ± SD RIS 3.5 ± 1.6), satisfaction with current disease-modifying antirheumatic drugs (mean ± SD RIS 3.4 ± 1.4), and current number of painful joints (mean ± SD RIS 3.4 ± 1.4). Factors influencing the decision to escalate care differ between rheumatologists and patients. Better communication between patients and their physicians may improve treatment planning in RA patients with active disease.

Prevalence of and predictive factors for sustained disease‐modifying antirheumatic drug–free remission in rheumatoid arthritis: Results from two large early arthritis cohorts

Remission has become an attainable goal of rheumatoid arthritis (RA) treatment, especially since the advent of biologic antirheumatic therapy. Because little is known about patients who achieve disease remission with conventional treatment, we used 2 large independent inception cohorts to study the prevalence of and predictive factors for disease-modifying antirheumatic drug (DMARD)-free sustained remission after treatment with conventional therapy. Remission of disease was assessed in 454 patients from the Leiden Early Arthritis Clinic (EAC) and in 895 patients from the British Early Rheumatoid Arthritis Study (ERAS) who fulfilled the American College of Rheumatology 1987 revised criteria for the classification of RA and were treated with conventional therapy. Sustained DMARD-free remission was defined as fulfilling the following criteria for at least 1 year: 1) no current DMARD use, 2) no swollen joints, and 3) classification as DMARD-free remission by the patient's rheumatologist. Predictive factors were identified by Cox regression analysis. Sustained DMARD-free remission was achieved by 68 of 454 patients (15.0%) in the Leiden EAC and by 84 of 895 patients (9.4%) in the ERAS. Six factors were associated with sustained DMARD-free remission in both cohorts: acute onset, short symptom duration before inclusion, not smoking, little radiographic damage at baseline, absence of IgM rheumatoid factor (IgM-RF), and absence of HLA shared epitope alleles. In the ERAS, low disease activity at baseline was also predictive of remission. Multivariate analyses revealed symptom duration and the absence of autoantibodies (anti-cyclic citrullinated peptide 2 and IgM-RF) as independent predictors. Sustained DMARD-free remission in RA patients treated with conventional therapy is not uncommon. Symptom duration at presentation and the absence of autoantibodies are associated with sustained DMARD-free remission.

Treatment of psoriatic arthritis with etanercept, a tumour necrosis factor antagonist

Psoriatic arthritis (PsA) is a chronic spondylarthritis that occurs in ∼ 23% of plaque psoriasis sufferers. Traditional treatments for rheumatoid arthritis have been used as the first therapeutic approach to treat this inflammatory disease, which has both joint and skin manifestations. However, due to the inefficiency of current disease-modifying antirheumatic drugs and non-steroidal anti-inflammatory drugs in stopping the progression of the joint disease, biologics have emerged as a hopeful alternative to PsA therapy. Etanercept was the first approved tumour necrosis factor-alpha (TNF-α) inhibitor for reducing the signs and symptoms of PsA, as well as preventing the progression of the disease. Etanercept is a fully human, soluble, dimeric fusion protein that has the ability to bind to two molecules of TNF, thereby rendering them biologically inactive. Two clinical trials have demonstrated that etanercept is generally a safe, efficacious and well-tolerated biologic therapy for the treatment of PsA.

A survey of British rheumatologists' DMARD preferences for rheumatoid arthritis.

To determine the current disease-modifying anti-rheumatic drug (DMARD) preferences of UK consultant rheumatologists. A questionnaire was sent in May 2002. We asked which DMARD(s) was most frequently preferred first and sought the most typical sequence of DMARDs, including DMARD combinations. Also we determined the extent to which prognostic and other factors influenced treatment choices. Comments were invited, written responses abstracted and key themes identified. After two mailings, 331 (of 460; 72%) suitable questionnaires were returned. Ninety-five per cent (315/331) preferred methotrexate (154, 46.5%) or sulphasalazine (144, 43.5%) or either of these two (17, 5%) as first-choice agent. Of those who chose methotrexate first, 80% (123/154) ranked sulphasalazine second, 45% (55/123) combined sulphasalazine and methotrexate and 49% (27/55) then added hydroxychloroquine to this combination, in active disease. Of those who chose sulphasalazine first, 95% (137/144) ranked methotrexate second, 75% (113/150) preferring methotrexate monotherapy and 12% (18/150) the combination with sulphasalazine. Rheumatologists who preferred sulphasalazine first more commonly used subsequent DMARDs singly than those who started with methotrexate (P < 0.0001). Leflunomide was more commonly preferred than intramuscular gold as third choice (52/145 vs 29/145; P < 0.003). The most popular sequence of DMARDs was methotrexate or sulphasalazine, singly or in combination, leflunomide, intramuscular gold and anti-tumour necrosis factor therapy. Poor prognostic factors influenced DMARD choice, but patient occupation and drug costs did not. Methotrexate has displaced other DMARDs, especially sulphasalazine, as agent of first choice and newer agents have displaced older DMARDs. Whether the expressed preference for particular DMARDs accurately reflects actual use, and is optimal in rheumatoid arthritis, remains to be determined.

A prospective, clinical and radiological study of early psoriatic arthritis: an early synovitis clinic experience.

To determine the clinical presentation and clinical and radiological outcome of early psoriatic arthritis (PsA) at 1 and 2 yr. Patients with PsA were assessed at the St. Vincent's University Hospital Early Synovitis Clinic. Standardized clinical and laboratory assessment was performed at presentation and 1- and 2-yr follow-up. Radiographs of the hands and feet were evaluated in chronological order by two trained observers using the Sharp method modified to include the distal interphalangeal (DIP) joints. A total of 129 (12.7%) of 1018 patients were diagnosed with PsA [mean age at onset of arthritis was 40.4 yr (range 11-76); mean duration of disease was 9.9 months (range 0.3-48); 52 oligoarticular, 77 polyarticular]. Means and standard deviations of indices of disease activity at presentation were: 10-cm visual analogue scale = 4.8 +/- 2.7, HAQ score = 0.71 +/- 0.64, ACR functional class III/IV = 41 (35%), Ritchie Articular Index = 5.6 +/- 6, swollen joint count = 6.9 +/- 8, erythrocyte sedimentation rate = 24 +/- 26.4 mm/h, C-reactive protein = 27.6 +/- 58.5 mg/l. At presentation, 49 (38%) patients had peripheral enthesopathy, 13 patients (10%) had inflammatory spine pain and 50 (39%) patients had DIP involvement. A total of 119 had psoriasis at the time of presentation [plaque psoriasis in 112 (94%), mean age of psoriasis onset was 29.8 +/- 16.2 yr, nail dystrophy present in 78 patients (67%)]. At 1 yr of follow-up, 119 (92%) patients were reassessed and 70 (59%) were taking a disease-modifying anti-rheumatic drug (DMARD). At 2 yr, 97 (75%) patients were reassessed and 54 (56%) were taking a DMARD. Despite considerable improvement in inflammation and function scores, only 31 (26%) patients were in remission at 1 yr with 20 (21%) in remission at 2 yr. There was a low rate of DMARD-free remission [14 (12%) at 1 yr and 11 (11%) at 2 yr]. Radiographs of hands and feet were obtained for 117 (91%) patients at presentation and 86 (67%) patients at a median follow-up of 24 months (range 11-56); 47% of patients had joint erosions in hands or feet at follow-up with a mean Sharp erosion score of 3 (0) +/- 5.2 (range 0-25) and a mean Sharp narrowing score of 3.2 (0) +/- 7.5 (range 0-48). This study confirms that PsA is a chronic, progressive disease in the majority of patients. Despite clinical improvement with current DMARD treatment, PsA results in radiological damage in up to 47% of patients at a median interval of 2 yr.

Treatment-induced remission in rheumatoid arthritis patients is characterized by a reduction in macrophage content of synovial biopsies.

To document the change in synovial membrane macrophage and T-lymphocyte content in rheumatoid arthritis (RA) patients who achieve remission induced by disease-modifying anti-rheumatic drugs (DMARDs). Arthroscopic synovial biopsies were taken from four to seven sites around a knee joint in 13 patients with RA before and at regular intervals after commencing treatment with a DMARD. The cellular content of synovial membrane biopsies taken at regular intervals for a period of up to 3 yr after commencing treatment was quantitated by routine histopathology and immunohistochemical labelling with anti-macrophage (CD68) and anti-T lymphocyte (UCHL-1) antibodies. Synovial biopsies were quantitated with a validated semiquantitative scoring system and video image analysis. Nine patients obtained clinical remission, as defined by American College of Rheumatology (ACR) criteria. The changes that occurred in the synovial biopsies included a reduction in lining layer thickness, reduced vascularity and cellular infiltrate. The most significant reduction in cellular infiltrate was in the lining layer macrophages, with less dramatic change in the subintimal macrophage infiltrate. Although there was a reduction in CD45 Ro-positive T lymphocytes in the synovial membranes of patients who attained ACR-defined disease remission, it was less significant than the reduction in macrophage content of the synovial membranes and tended to plateau at a reduced level of T-cell infiltration. Remission in RA patients is characterized by a predominant reduction in macrophage content of the synovial membrane, suggesting that current DMARDs may target this cell and its inflammatory mediators.