Number Of Rheumatoid Arthritis Patients Research Articles

E012 An audit examining specialist referral for osteoporosis treatment for rheumatoid arthritis patients using new NOGG (National Osteoporosis Guideline Group) Guidelines 2022

Abstract Background/Aims Major osteoporotic fractures remain an important cause of mortality and morbidity. Rheumatoid arthritis patients have significantly increased risk of fracture. New NOGG 2022 guidance recommends specialist referral for certain patients based on FRAX and other risk factors, to consider parenteral and anabolic treatment. Our aim was to assess how many rheumatoid arthritis patients would now require specialist referral. Methods We identified 38 patients with rheumatoid arthritis who had been referred for DEXA scanning in January 2022. FRAX was used to estimate fracture risk, this was then adjusted as per NOGG guidance to account for risk factors not included in FRAX. Intervention thresholds from new and old guidance were compared. Results 90% of patients were female. Average age was 63.2 years. Mean major osteoporotic fracture risk is 15.6 and mean hip fracture risk is 4.7 over 10 years. 31.6% had previous fracture, 8% had recent fracture, and 8% had vertebral fractures. 26.3% were taking steroids, 10.5% were taking high dose steroids. 5% had received parenteral treatment at time of audit. Conclusion Rheumatoid arthritis patients have an increased fracture risk and therefore require robust bone protection/fracture risk reduction. This is because of a combination of disease pathogenesis, and concurrence of fracture risk factors. Our cohort reflected this; fracture risk was high and risk factors, particularly steroid use, and previous fracture, were common. Under previous guidance, some patients would eventually be referred to a specialist at the discretion of their physician. New NOGG guidance recommends referral as first line for certain patients. When applied to this cohort, we can see that a significant number of patients would be referred to a specialist. This represents a significant shift away from oral therapies and towards consideration of specialist treatment. Under new guidance, a significant number of rheumatoid arthritis patients need specialist referral. This requires a substantial number of resources and means that parenteral therapies will have a much larger place in osteoporosis management. Disclosure A. Rauf: None. K. Moss: None.

The First Effect of COVID-19 Pandemic on Starting Biological Disease Modifying Anti-Rheumatic Drugs: Outcomes from the TReasure Real-Life Database.

The coronavirus disease 2019 pandemic has been resulting in increased hospital occupancy rates. Rheumatic patients cannot still reach to hospitals, or they hesitate about going to a hospital even they are able to reach. We aimed to show the effect of the first wave of coronavirus disease 2019 pandemic on the treatment of biological disease-modifying anti-rheumatic drugs in patients with rheumatoid arthritis or spondyloarthritis. Patients were divided into three groups as follows: pre-pandemic (Pre-p: starting on biological disease-modifying anti-rheumatic drug therapy for the first time within 6 months before March 11, 2020); post-pandemic A (Post-p A: starting on biological disease-modifying anti-rheumatic drug therapy for the first time within the first 6 months after March 11, 2020); post-pandemic B (Post-p B: starting on biological disease-modifying anti-rheumatic drug therapy for the first time within the second 6 months). The number of rheumatoid arthritis patients in the Post-p A and B groups decreased by 51% and 48%, respectively, as compared to the Pre-p group similar rates of reduction were also determined in the number of spondyloarthritis patients. The rates of tofacitinib and abatacept use increased in rheumatoid arthritis patients in Post-p period. The number of rheumatoid arthritis and spondyloarthritis patients starting on biological disease-modifying anti-rheumatic drugs for the first time decreased during the first year of the coronavirus disease 2019 pandemic.

Long-term passages of human clonal mesenchymal stromal cells can alleviate the disease in the rat model of collagen-induced arthritis resembling early passages of different heterogeneous cells.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease of unknown cause. The interaction of immune system cells and the secretion of inflammatory cytokines with synovial cells leads to severe inflammation in the affected joints. Currently, medications, including non-steroidal anti-inflammatory drugs, glucocorticoids, and more recently, disease-modifying anti-rheumatic drugs, are used to reduce inflammation. However, long-term use of these drugs causes adverse effects or resistance in a considerable number of RA patients. Recent findings revealed the safety and efficacy of mesenchymal stromal cells (MSCs)-based therapies both in RA animal models and clinical trials. Here, the beneficial effects of bone marrow-derived heterogeneous MSCs (BM-hMSCs) and Wharton jelly-derived MSCs (WJ-MSCs) at early passages were compared to BM-derived clonal MSCs (BM-cMSCs) at high passage number on a rat model of collagen-induced arthritis. Results showed that systemic delivery of MSCs significantly reversed adverse changes in body weight, paw swelling, and arthritis score in all MSC-treated groups. Radiological images and histological evaluation demonstrated the therapeutic effects of MSCs. There was a decrease in serum level of anti-collagen type II immunoglobulin G and the inflammatory cytokines interleukin (IL)-1β, IL-6, IL-17, and tumor necrosis factor-α in all MSC-treated groups. In contrast, an increase in inhibitory cytokines transforming growth factor-β and IL-10 was seen. Notably, the long-term passages of BM-cMSCs could alleviate RA symptoms similar to the early passages of WJ-MSCs and BM-hMSCs. The importance of BM-cMSCs is the potential to establish cell banks with billions of cells derived from a single donor that could be a competitive cell-based therapy to treat RA.

The EVALUATION OF THE USE OF ANTI-INFLAMMATORY DRUGSIN PATIENTS RHEUMATOID ARTHRITIS OUTPATIENT AT GRANDMED HOSPITAL LUBUK PAKAM

Rheumatoid arthritis is an autoimmune disease characterized by inflammation of the joints that can become chronic. Rational use of drugs aims to ensure that patients get safe and effective treatment in the right time frame and at an affordable price according to their needs In the outpatient facility of Lubuk Pakam Hospital, patients experience symptoms such as pain, inflammation, morning joint stiffness and difficulty moving at appropriate doses. This study aims to aim to obtain an objective picture or picture of the situation. Data collection was carried out retrospectively, namely by observing the medical records of rheumatoid arthritis patients at Grandmed Lubuk Pakam Hospital in 2021. A total of 13 (56.5%) female patients and 10 (56.5%) (43.5%) male patients, according to the number of rheumatoid arthritis patients at the outpatient facility of GrandMed Lubuk Pakam Hospital in 2021. This makes the inclusion criteria for all anti-inflammatory agents incomplete in rheumatoid arthritis and the exclusion criteria for all medical records in rheumatoid arthritis patients. Analysis of data based on age, gender, rationality of the drug, correct indications, correct patient, correct drug, correct dosage. The Outpatient Study of GrandMed Lubuk Pakam Hospital 2021 is: Correct Indications (100%), Correct Patients (100%), Correct Drugs (100%), Correct Dosage (91.3%). The treatment of patients with rheumatoid arthritis at GrandMed Lubuk Pakam Hospital can still be said to be fully good

POS1442 THE PREVALENCE OF RHEUMATOID ARTHRITIS IN WESTERN AUSTRALIA EXTRAPOLATED FROM HOSPITALISATION AND BIOLOGICAL THERAPY USAGE DATA

BackgroundRheumatoid arthritis (RA) is a heterogeneous chronic autoimmune disease that affects the synovial joint lining and may result in permanent joint destruction, premature death, and socio-economic burden.1 Although RA is one of Australia’s national health priority areas and gathering information about the RA burden of disease was one of the national action plans2, no published epidemiological study adequately describes RA prevalence and risk factors for frequent hospitalisations in Western Australia (WA) to date. An accurate prevalence estimate of this disease offers a framework for predicting present and growing healthcare service requirements in the future.3ObjectivesWe estimated RA period prevalence and identified risk factors of frequent RA hospitalisations, using linked administrative health and state-specific Australian Pharmaceutical Benefits Scheme (PBS) datasets in WA from 1995–2014.MethodsRA prevalence was calculated per 1000 hospital separations and biological therapy users. RA patients were identified in the WA linked health dataset using ICD codes 714.0–714.9 and M05.00–M06.99. Dispensing data on biological therapy for RA were obtained from PBS records and converted to defined daily doses/1000 population/day. Multivariate logistic regression was used to analyse risk factors for frequent RA hospitalisations (>2/year), controlling for sex, age, and geographic locations.ResultsA total of 17,125 RA patients were admitted to WA hospitals between 1995–2014. The total number of RA hospital separations was 50,353, averaging three hospitalisations per patient over 20 years. The RA period prevalence was 3.4 per 1,000 separations (0.34%), while the RA period prevalence based on biological therapy use was 0.36%. The corrected RA prevalence based on biological therapy usage was 0.36% and 0.72% for the 2005–2009 and 2010–2014 periods, respectively (Table 1). Female gender, age 60–69 years, and living in rural areas were all risk factors for frequent RA hospitalisations.Table 1.Total number of Rheumatoid Arthritis patients in Western Australia taking a standard dose daily (DDD) of RA biological therapy from 1995 to 2014.YearTotal RA bDMARDs utilisation (DDD/1000 population/day)WA general populationPrevalence of RA bDMARDs use in WA population (%)Number of RA patients use standard dose daily of bDMARDs at WA20030.011,952,7410.001420040.081,979,5420.0115820050.162,011,2070.0232920060.232,050,5810.0247620070.312,106,1390.0364320080.502,171,7000.051,09420090.602,240,2500.061,33820100.592,290,8450.061,36120110.632,353,4090.061,47520120.772,425,5070.081,85920130.662,486,9440.071,64920141.002,517,6080.102,510Abbreviations: bDMARDs, biologic disease-modifying anti-rheumatic drugs included Abatacept, Adalimumab, Certolizumab, Etanercept, Golimumab, Infliximab, Rituximab, Tocilizumab; DDD, defined daily doses; RA, Rheumatoid arthritis; WA, Western Australia.ConclusionBased on hospital and biological therapy data, the minimal prevalence of RA in Western Australia is 0.34–0.36%, which falls within the literature range. Older female RA patients in rural areas were more likely to be hospitalised, suggesting unmet needs in primary care access.

SCORE2 Assessment in the Calculation of Cardiovascular Risk in Patients with Rheumatoid Arthritis.

Patients with rheumatoid arthritis (RA) are at increased risk for cardiovascular disease (CVD). Risk chart algorithms, such as the Systematic Coronary Risk Assessment (SCORE), often underestimate the risk of CVD in patients with RA. In this sense, the use of noninvasive tools, such as the carotid ultrasound, has made it possible to identify RA patients at high risk of CVD who had subclinical atherosclerosis disease and who had been included in the low or moderate CVD risk categories when the SCORE risk tables were applied. The 2003 SCORE calculator was recently updated to a new prediction model: SCORE2. This new algorithm improves the identification of individuals from the general population at high risk of developing CVD in Europe. Our objective was to compare the predictive capacity between the original SCORE and the new SCORE2 to identify RA patients with subclinical atherosclerosis and, consequently, high risk of CVD. 1168 non-diabetic patients with RA and age > 40 years were recruited. Subclinical atherosclerosis was searched for by carotid ultrasound. The presence of carotid plaque and the carotid intima media wall thickness (cIMT) were evaluated. SCORE and SCORE2 were also calculated. The relationships of SCORE and SCORE2 to each other and to the presence of subclinical carotid atherosclerosis were studied. The correlation between SCORE and SCORE2 was found to be high in patients with RA (Spearman’s Rho = 0.961, p < 0.001). Both SCORE (Spearman’s Rho = 0.524) and SCORE2 (Spearman’s Rho = 0.521) were similarly correlated with cIMT (p = 0.92). Likewise, both calculators showed significant and comparable discriminations for the presence of carotid plaque: SCORE AUC 0.781 (95%CI 0.755–0.807) and SCORE2 AUC 0.774 (95%CI 0.748–0.801). Using SCORE, 80% and 20% of the patients were in the low or moderate and high or very high CVD risk categories, respectively. However, when the same categories were evaluated using SCORE2, the percentages were different (58% and 42%, respectively). Consequently, the number of RA patients included in the high or very high CVD risk categories was significantly higher with SCORE2 compared to the original SCORE. (p < 0.001). In conclusion, although predictive capacity for the presence of carotid plaque is equivalent between SCORE and SCORE2, SCORE2 identifies a significantly higher proportion of patients with RA who are at high or very high risk of CVD.

Differential mitochondrial genome in patients with Rheumatoid Arthritis

Background Mitochondria play an important role in cell survival, function and lineage differentiation. Changes in mitochondrial DNA (mtDNA) may control mitochondrial functions and thus may impart an alternative cellular state thereby leading to a disease condition in the body. Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease wherein immune cells become self-reactive causing joint inflammation, swelling and pain in patients. The changes in mtDNA may alter cellular functions thereby directing the immune cells towards an inflammatory phenotype in RA. Therefore, it becomes pertinent to identify changes in mtDNA sequence in immune cells of RA patients to understand the pathogenesis and progression of RA. Methods mtDNA from peripheral blood mono-nuclear cells (PBMCs) of 23 RA patients and 17 healthy controls (HCs) were sequenced using next-generation sequencing (NGS). Further, single nucleotide polymorphisms (SNPs) and other variable changes in mtDNA hypervariable and coding regions, amino acid changes with a putative impact on disease, levels of heteroplasmy, copy number variations and haplogroup analysis in RA patients and HCs were analysed and compared to identify any association of mtDNA changes and RA disease. Results A total of 382 single nucleotide mtDNA variants were observed, 91 (23.82%) were present in hypervariable region and 291 (76.18%) in coding region of patients and HC. The variant 513 GCA > ACA, with G present in HVR-III, known to control the mitochondrial translation function, was significantly present in RA patients. The CYTB gene had larger number of SNPs in HC samples while RNR2 was more variable in RA patients. A non-synonymous heteroplasmy in ND1 gene was found at a single nucleotide position 3533 in an increased number of RA patients as compared to the controls. A significant increase in mtDNA duplication and a higher frequency of the haplogroup U was also characteristic of RA. Also, the presence of SNPs in mitochondrial tRNA genes at two positions 12308 A > G and 15924 A > G were found to be pathogenic. Conclusion We herein observed an altered mtDNA sequence in immune cells of RA patients and thus a possible role of mitochondrial genome in the development of RA. The observed nucleotide changes in mtDNA control region, RNR2 gene, increased heteroplasmy and mtDNA duplication in RA patients may alter sites for transcription factor binding thereby influencing mtDNA gene expression, as well as copy numbers thereby affecting the mitochondrial proteins and their functions. These changes in mtDNA could be one of the probable reasons among many leading to the progression of RA.

Epidemiological characteristics of rheumatoid arthritis in Japan: Prevalence estimates using a nationwide population-based questionnaire survey

Objectives: To elucidate the epidemiological characteristics of patients with rheumatoid arthritis (RA) in Japan using data from the Comprehensive Survey of Living Conditions, a nationwide questionnaire survey conducted in 2016.Methods: In total, 222,365 men and 245,251 women aged ≥16 years were included in the study. RA patients were defined as those who reported ‘currently receiving treatment for RA at hospitals, clinics, or a facility for Japanese traditional massage, acupuncture, moxibustion, or judo-orthopedics.’ The number of RA patients was estimated from the age-specific prevalence and total Japanese population in 2016. Further, the prevalence of individuals experiencing difficulties in activities of daily living due to health problems and those with mental distress as evaluated by K6 Scale was examined.Results: The estimated number and prevalence of RA in Japan with 95% confidence interval was 822 (768–880) thousand and 0.75% (0.70–0.80%). The population peaked in the late 60s, and the prevalence continued increasing until the early 80s, regardless of sex. Compared with non-RA participants, RA patients were more likely to experience difficulties in activities and to be distressed.Conclusion: High prevalence of RA in older age and mental and physical burden among RA patients were confirmed.

PMS112 - PATIENT AND RHEUMATOLOGIST PREFERENCES FOR THE ATTRIBUTES OF RHEUMATOID ARTHRITIS TREATMENTS IN SPAIN. A DISCRETE CHOICE EXPERIMENT

Involving patients and incorporating their preferences in healthcare decision-making can contribute to treatment success. This study determinates the preferences of patients and rheumatologists for the attributes of rheumatoid arthritis (RA) treatments in Spain and evaluates patients’ preferences for shared decision-making (SDM). Preferences were determined using a discrete choice experiment (DCE). A literature review and 2 focus groups (patients=5; rheumatologists=4) were conducted to identify the attributes and levels to be included in the DCE. Seven attributes containing 2-4 levels of response were presented in 8 different scenarios. The relative importance (RI) given by rheumatologists and patients to the attributes were estimated using conditional logit model. Patient preferences for SDM were reported through an ad-hoc questionnaire. A total of 90 rheumatologists [professional exercise (years): 18.11 (SD:9.02), number of RA patients visited/week: 24.40 (SD:15.33)]; and 137 patients [83.94% female, age (years): 47.45 (SD:10.73), time since diagnosis (years): 14.23 (SD:11.78), time on current treatment (years): 6.20 (SD:7.82), HAQ score: 1.19 (SD:0.68)] participated in the study. The estimated RI were: mode of administration: R:25.23%, P:25.00%; time in optimal quality of life: R:23.41%, P:35.05%; time to onset of treatment action: R:16.24%, P:13.56%; substantial improvement in symptoms: R:13.15%, P:3.62%; severe adverse events: R:10.89%, P:11.20%; added cost for treatment: R:6.93%, P:10.66%; and mild adverse effects: R:4.16%, P:0.91%. Regarding SDM, 31.85% of the patients reported that they evaluated the therapeutic options with their doctor, who made the final decision. 37.50% indicated that they would like to decide their treatment after evaluating the different options with the doctor. For rheumatologists, in addition to efficacy, treatment mode of administration and its time to onset the action are decision-making drivers. For patients, the mode of administration and the efficacy (time in optimal quality of life) are determinants in treatment selection. Patients would prefer more involvement in treatment decisions-making.

Shoulder Arthroplasty in Patients with Rheumatoid Arthritis: A Population-Based Study Examining Utilization, Adverse Events, Length of Stay, and Cost.

It has been suggested that the utilization of joint arthroplasty in patients with rheumatoid arthritis (RA) is decreasing; however, this observation is largely based upon evidence pertaining to lower-extremity joint arthroplasty. It remains unknown if these observed trends also hold true for shoulder arthroplasty. The purpose of this study is to utilize a nationally representative population database in the US to identify trends in the utilization of shoulder arthroplasty among patients with RA. Secondarily, we sought to determine the rate of early adverse events, length of stay, and hospitalization costs associated with RA patients undergoing shoulder arthroplasty and to compare these outcomes to those of patients without a diagnosis of RA undergoing shoulder arthroplasty. Using a large population database in the US, we determined the annual rates of shoulder arthroplasty (overall and individual) in RA patients between 2002 and 2011. Early adverse events, length of stay, and hospitalization costs were determined and compared with those of non-RA patients undergoing shoulder arthroplasty. Overall, we identified 332,593 patients who underwent shoulder arthroplasty between 2002 and 2011, of whom 17,883 patients (5.4%) had a diagnosis of RA. Over the study period, there was a significant increase in the utilization of shoulder arthroplasty in RA patients, particularly total shoulder arthroplasty. Over the same period, there was a significant increase in the number of RA patients who underwent shoulder arthroplasty with a diagnosis of rotator cuff disease. There were no significant differences in adverse events or mean hospitalization costs between RA and non-RA patients. Non-RA patients had a significantly shorter length of stay; however, the difference did not appear to be clinically significant. In conclusion, the utilization of shoulder arthroplasty in patients with RA significantly increased from 2002 to 2011, which may partly reflect a trend toward management of rotator cuff disease with arthroplasty rather than repair.

Improving patient flow of people with rheumatoid arthritis has the potential to simultaneously improve health outcomes and reduce direct costs

BackgroundIn our current economic climate of scarce resources there is a lot of debate around the best - and most efficient - way of delivering care, which points patients towards the right physician at the earliest opportunity.The aim of the study was to assess whether an improvement in the interdisciplinary management of rheumatoid arthritis (RA) has the potential to simultaneously improve health outcomes and reduce costs.MethodsIn a first step, we modelled the ways which lead patients with RA to the correct diagnosis, and the relevant specialist, respectively. On average, a patient experiences 3 GP visits before referral to a specialist. We compared this situation against a reconfiguration of current practice towards a more proactive identification and referral method with initiation of care by a rheumatologist early in the disease. We evaluated the impact of this reconfiguration on the number of RA patients diagnosed and the costs associated with the diagnostic process.ResultUsing data on epidemiology and Austrian practice patterns, we estimate a total of 5294 people with undifferentiated arthritis per year, of which 1765 suffer from RA. Modelling for diagnostic accuracy, we found that 1200 of these patients are initially misdiagnosed in a primary care setting and 95 at a rheumatologist. Our model found that a reconfiguration of current practice towards an approach of more integrated care has the potential to be not only cost-effective, but cost-saving: EUR 100,188 could be saved annually by exclusively adopting the new approach.ConclusionsOur results show that by better directing the flow of people with RA, simultaneous clinical and economic benefits may be reaped:.

Correlation Between the Oral Manifestations of Rheumatoid Arthritis Patients on Different Treatments with The Clinical Disease Activity

Objective:Toevaluate the oral findings and correlating the oral findings with the clinical disease activity index. Subjects, Materials and Methods:This cross- sectional studyincludedeighty-five rheumatoid arthritis patients. Twenty-five patients were on Methotrexate, thirty patients on Etanercept and thirty patients were on a combination of Methotrexate and Etanercept. Each patient was examined to calculate the clinical disease activity index and to detect any oral finding. Results: The highest summation of rheumatoid arthritis patients was presented with a high clinical disease activity index, while the number of those with low disease activity index was the lowest. Oral dryness showed to be the most common oral findings (60%) followed by tempromandibular joint disorders (31.8%) then aphthous ulcerations (9.4%) and glossitis (5.8%), while the lichenoid drug reaction, angular chelitis and geographic tongue were the less commonly seen findings (1.1% for each). Most of the oral findings were seen in patients treated with Etanercept or Methotrexate alone, while the patients treated with a combination of them had less oral side effects. A higher number of rheumatoid arthritis patients with oral findings were showing high and moderate disease activity. Conclusions: The oral dryness, tempromandibular joint disorders and aphthous ulcerations were the main oral manifestations found in rheumatoid arthritis patients. Angular chelitis positively correlate with the increasing in

One-year safety of ibuprofen/famotidine fixed combination versus ibuprofen alone: pooled analyses of two 24-week randomized, double-blind trials and a follow-on extension

Objective:To evaluate the safety of the fixed combination of ibuprofen and famotidine compared with ibuprofen alone from two 24-week, multicenter, double-blind trials designed to evaluate the comparative incidence of endoscopically documented upper gastrointestinal ulcers and a 28-week double-blind extension study.Research design and methods:Safety was analyzed by pooling data from the two double-blind trials and the follow-on study. Safety was assessed by monitoring the incidence, causality, and severity of adverse events (AEs).Results:In the pivotal efficacy and safety trials, discontinuation rates due to any cause and dyspepsia were significantly lower for the ibuprofen/famotidine combination versus ibuprofen alone. Other than dyspepsia, gastrointestinal and cardiovascular AEs of special interest were similar. Events judged to be treatment related were significantly lower with the ibuprofen/famotidine combination (20.6% vs. 25%). In the safety extension population, there were no differences in the discontinuation rates and the reporting of AEs or serious AEs (SAEs) between the two groups. Gastrointestinal-related events were similar between the groups. Incidence of cardiovascular-related AEs of special interest were 11% (ibuprofen/famotidine) and 2% (ibuprofen) (p = 0.06), possibly due to a higher number of rheumatoid arthritis patients in the combination group. Of these, 80% were reports of hypertension (8% ibuprofen/famotidine vs. 2% ibuprofen). Three cases of hypertension in the ibuprofen/famotidine group were considered treatment related. The probability of a cardiovascular event decreased during days 112–167 of treatment and remained low with continued treatment.Conclusions:One-year safety data from two pivotal trials and a long-term extension study indicate that the ibuprofen/famotidine combination demonstrates a favorable gastrointestinal safety profile and more patients continued on therapy compared to ibuprofen alone. No new safety signals have been identified. These data offer additional evidence supporting a new therapeutic option to improve gastrointestinal safety and adherence for patients who require long-term ibuprofen.

FRI0437 How do we Treat Patients with Focus Score ≥1, but not Consistent with the New American College of Rheumatology Classification Criteria for SjÖGren's Syndrome? Evaluation from Study in Japanese Patients

BackgroundOne of the criteria for Sjögren's syndrome (SS) is focal lymphocytic infiltration in minor salivary gland biopsy (MSGB). Few studies have revealed that the proportion of patients with focus score...

SAT0127 Gout and RA: not Such A Rare Coexistence after All?

BackgroundAccording to the current rheumatology literature, the simultaneous occurrence of rheumatoid arthritis (RA) and gout is rare and only a few cases have been reported to date.[1] However, clinical practice...

Moving the Injectable Methotrexate Service Closer to Home: A Practice Development Initiative

The aim of this practice development project was to make it quicker and easier for patients to switch to subcutaneous (s/c) methotrexate and thereby introduce a nurse-led methotrexate clinic into a district general hospital, which would make the best use of the advanced knowledge and skills of the rheumatology specialist nurses; empower patients and improve their experience; and introduce cost savings for the Trust. Over a period of four months, meetings were held with pharmacists, clinicians, administrative and support staff to formulate a plan to introduce the changes and agree the benefits to patients. A detailed plan for the practice development project addressed the procedures to follow, the safety issues for patients and the revision of current documentation. A review of service in the year before and after the change revealed that the number of rheumatoid arthritis patients who had switched to s/c methotrexate had increased by 80%. This was a significant difference (p = 0.049), which strongly suggested that the change in service was the reason for the increased number of patients who were able to switch their route of administration of methotrexate. This project demonstrated that not only do nurse specialists have the skills to make clinical decisions and judgements, prescribe medications and escalate therapies with no detriment to the patients, but also that this practice can lead to a more efficient and effective service, at a reduced cost to the Trust.

Opinion of Japanese rheumatology physicians on methods of assessing the quality of rheumatoid arthritis care

To examine the opinion of rheumatology physicians in Japan regarding desirable quality assessment methods. We conducted a cross-sectional self-administered mail survey on a random sample of physicians and surgeons registered with the Japan Rheumatism Foundation. In the survey, respondents were asked to rank seven proposed assessment methods for the quality of rheumatoid arthritis care, namely patient satisfaction, risk-adjusted outcomes such as complication incidence and admission rate, guideline compliance, waiting time at clinics, voting by local general practitioners, degree of newspaper and magazine reportage, and volume of patients receiving treatment for rheumatoid arthritis. Among 531 respondents (response rate 48%), the respondents ranked patient satisfaction most favourably (mean rank 1.6), followed by complication/admission rate and number of patients. Guideline adherence was ranked almost the same as voting by local physicians. Waiting time and media reportage were not considered good methods for quality evaluation. Ranking distribution did not differ by working facility or place, volume of patients or years in practice. Multivariate analysis revealed that respondents who care for a large number of rheumatoid arthritis patients (>40 regular patients) were less likely to rank guideline adherence highly (first to third) than those who care for few patients (≤ 10 regular patients), with an odds ratio of 0.38 (P < 0.01) after adjustment for other variables. A majority of Japanese rheumatology physicians consider patient satisfaction the most trustworthy method of assessing the quality of rheumatoid arthritis care. Future research should explore convincing methods of assessing the technical quality of rheumatoid arthritis care.

Aktuelle Trends in Design und Entwicklung monoklonaler Antikörper gegen Entzündungsmediatoren zur Therapie der rheumatoiden Arthritis

As mediators of inflammation, cytokines contribute significantly to both the development and the extent of the inflammatory response in rheumatoid arthritis (RA). In addition, they regulate the differentiation of various cells involved in the pathogenesis of this disease. Tumour necrosis factor alpha (TNF alpha), interleukin (IL)-1 and IL-6 constitute prominent examples of such inflammatory cytokines and have been shown to play an important role in RA. As a consequence, the use of recombinant antibodies targeting these cytokines has revolutionized the treatment of RA. However, a considerable number of RA patients do not respond adequately to therapy with such biologics. Based on this notion, this article summarizes current trends in the design and development of monoclonal antibodies against inflammatory mediators. These include the identification of alterative target structures for anti-cytokine therapies, the specific modification of the antigen-binding CDR of therapeutic antibodies to reduce immunogenicity, alterations of the Fc part and the development of modified antibody fragments to improve the pharmacokinetics and to avoid non-specific immune reactions. Beyond that, efforts are undertaken to optimize the cost of these therapies.

Genetic variants that predict response to anti-tumor necrosis factor therapy in rheumatoid arthritis: current challenges and future directions

Tumor necrosis factor alpha (TNF) inhibitors are a mainstay of treatment in rheumatoid arthritis, yet there are no effective clinical or biomarker predictors of which patients will respond. Here we review genetic association studies conducted to search for DNA biomarkers of response to anti-TNF therapy. The entirety of genetic association studies to date that focus on response to anti-TNF therapy has been limited to a small number of genetic variants within a few candidate genes (primarily within the major histocompatibility complex region). Moreover, these studies have been conducted in a relatively small number of rheumatoid arthritis patients (approximately 1000 patients across all studies combined). From these studies, no single genetic factor is associated unequivocally with treatment response, although some studies suggest that alleles within the major histocompatibility complex may influence response. Additional studies are required to investigate the genetic basis of response to anti-TNF therapy. These studies should include an unbiased search of DNA variation across the human genome--now feasible through cost-effective genome-wide association studies--and be conducted in large patient collections powered to detect modest effect sizes.

Emerging biologic therapies in rheumatoid arthritis: cell targets and cytokines

Biologic therapy for rheumatoid arthritis targets specific molecules, both cell-bound and soluble, that mediate and sustain the clinical manifestations of this complex disease. The aim of all the therapeutic strategies is to achieve complete and sustained suppression of inflammation, in the absence of unacceptable short-term and long-term toxicity. Despite the success of the currently available biologic inhibitors of tumor necrosis factor-alpha and interleukin-1, a substantial number of rheumatoid arthritis patients are refractory to these treatments. The purpose of this review is to highlight recent clinical trials of emerging biologic treatments for rheumatoid arthritis. T cell co-stimulation has been targeted by the use of cytotoxic T lymphocyte-associated antigen 4-Ig, a genetically engineered fusion protein. In a large controlled clinical trial, this nondepleting approach was shown to achieve impressive clinical responses, without evidence of short-term toxicity. Likewise, rituximab, a B cell-deleting monoclonal antibody, was shown in a controlled clinical trial to have sustained benefit in patients with refractory rheumatoid arthritis. Despite profound B cell depletion with rituximab, there was an acceptable safety profile with this treatment. MRA, a monoclonal antibody that inhibits interleukin-6 by binding to its receptor interleukin-6R, demonstrated clinically significant improvement in rheumatoid arthritis and a particularly impressive reduction in the acute phase response. The response of rheumatoid arthritis to a wide spectrum of therapeutic strategies attests to the complexity and heterogeneity of the disease and provides further impetus for studies that use these therapies to enhance our understanding of disease pathogenesis.