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ID PMID Title PublicationDate abstract
24100773 [Economic evaluation of rheumathoid arthritis monotherapy with tocilizumab and adalimumab] 2013 Jul BACKGROUND: Tocilizumab (TCZ) was superior to adalimumab (ADA), as monotherapy, in reducing signs and symptoms of adult rheumatoid arthritis (RA) when methotrexate (MTX) treatment is poorly tolerated or inappropriate. The aim of the study was to analyze the cost-effectiveness of TCZ vs ADA in these patients. METHODS: Economic evaluation of the cost per response or remission of TCZ vs ADA from ADACTA (time horizon: 24 weeks). Clinical response criteria ACR or disease remission criteria, DAS28. PERSPECTIVE: National Health System. The costs included (acquisition, administration and monitoring of medicines; € 2012) were obtained from Spanish sources. Simple univariate sensitivity analyzes were performed. RESULTS: ACR20, ACR50 and ACR70 response rates with TCZ and ADA were obtained in 65% and 49.4% (p <0.01), 47.2% and 27.8% (p <0.01); and 32.5% and 17.9% (p <0.01) of patients, respectively. DAS28 remission occurred in 39.9% and 10.5%, respectively (p <0.0001). The cost per response was lower with TCZ than with ADA (ACR20: € 8,105 and € 11,553; ACR50: € 11,162 and € 20,529; ACR70: € 16,211 and € 31,882) respectively. The cost of DAS28 remission was € 13,204 and € 54,352, respectively. Treatment with TCZ was dominant (more effective, with lower costs vs ADA) in all scenarios analyzed. CONCLUSIONS: According to this analysis, in Spain TCZ monotherapy is an efficient strategy vs ADA for treating RA patients intolerant to MTX or in which there is inappropriate response.
25536122 Outcomes related to methotrexate dose and route of administration in patients with rheumat 2015 Mar OBJECTIVES: Methotrexate (MTX) is considered the 'anchor drug' in the therapy of rheumatoid arthritis (RA), yet many physicians do not optimise MTX regimens in spite of high RA disease activity. The recent development of an auto-injector for the subcutaneous (subQ) administration of MTX has prompted re-evaluation of MTX utilisation. The purpose of this systematic literature review is to determine the optimal dose, drug level, and route of administration for MTX in the context of relevant pharmacokinetics and pharmacogenomics. METHODS: A systematic literature review was performed in Medline searching specifically for randomised controlled trials, systematic reviews, case control and cohort studies evaluating outcomes related to MTX dose and route of administration. Articles fulfilling these inclusion criteria were reviewed. Data on MTX dose, route of administration, clinical response, drug levels and adverse events were evaluated. RESULTS: Our search identified 420 articles of which 6 were eligible for inclusion using the above criteria. These included 2 systematic reviews, 2 randomised open label trials, one longitudinal study and one retrospective cohort study. CONCLUSIONS: Efficacy and toxicity for MTX appear related to absorbed dose of MTX, not to route of administration. While bioavailability is greater for parenteral MTX, there is no evidence yet that splitting the oral dose of MTX is less advantageous, less safe or less tolerable than administering parenteral MTX. However, there appear to be modest benefits in beginning with higher doses of MTX, and switching to parenteral MTX when the clinical response to an oral dose is inadequate.
23203903 Decline of mean initial prednisone dosage from 10.3 to 3.6 mg/day to treat rheumatoid arth 2013 May OBJECTIVE: To analyze prednisone treatment from 1980-2004 in 308 patients with rheumatoid arthritis (RA), including 75 monitored over 4-8 years and 73 monitored over >8 years, for initial dose, long-term doses and effectiveness, and adverse events. METHODS: A database of all patients of a single rheumatologist included medications and Multidimensional Health Assessment Questionnaire (MDHAQ) scores at each visit. Proportions of patients whose initial prednisone dosages were >5, 5, or <5 mg/day were computed in 5-year periods: 1980-1984, 1985-1989, 1990-1994, 1995-1999, and 2000-2004. Mean changes in MDHAQ function, pain, and Routine Assessment of Patient Index Data 3 (RAPID3) scores were compared in patients treated with <5 versus ≥5 mg/day of prednisone; scores and adverse events were analyzed in quartiles by treatment duration of ≤1, 1.1-4, 4.1-8, and >8 years. RESULTS: In the respective 5-year periods, the mean initial prednisone dosages were 10.3, 6.5, 5.1, 4.1, and 3.6 mg/day, with >5 mg/day in 49%, 16%, 7%, 7%, and 3% of patients, 5 mg/day in 51%, 80%, 70%, 26%, and 10% of patients, and <5 mg/day in 0%, 4%, 23%, 67%, and 86% of patients. Most patients received early concomitant methotrexate after 1990, and prednisone <5 mg/day was maintained indefinitely. Patients treated with prednisone ≥5 mg/day had poorer clinical status as baseline and followup. MDHAQ scores improved similarly in patients treated with <5 or ≥5 mg/day. Primary adverse events were skin thinning and bruising. New hypertension, diabetes mellitus, and cataracts occurred in <10% of all patients, and <13% of those treated longer than 8 years. CONCLUSION: The data suggest that many patients with RA might be treated effectively with initial and long-term prednisone <5 mg/day, although further research and observational data are needed to characterize more fully effectiveness and safety.
24356474 Open-label observation of addition of etanercept versus a conventional disease-modifying a 2014 Jan BACKGROUND: Previous global studies examined etanercept (ETN) + methotrexate (MTX) for treatment of rheumatoid arthritis (RA), but included few subjects from Latin America. OBJECTIVE: The objective of this study was to compare the safety and efficacy of ETN + MTX versus a standard-of-care disease-modifying antirheumatic drug (DMARD) + MTX in Latin American subjects with moderate to severe active RA despite MTX therapy. METHODS: This open-label, active-comparator study (NCT00848354) randomized subjects 2:1 to ETN 50 mg/wk + MTX or investigator-selected DMARD (sulfasalazine or hydroxychloroquine) + MTX (ETN + MTX, n = 281; DMARD + MTX, n = 142). The primary end point was the proportion achieving American College of Rheumatology (ACR) 50 at week 24. Secondary end points included ACR20/70, disease activity score (DAS) 28 measures, and mean change in modified total Sharp score. Patient-reported outcomes were the Health Assessment Questionnaire, 36-item Short-Form, Hospital Anxiety and Depression Scale, Work Productivity and Activity Impairment: RA (WPAI:RA), and Caregiver Burden and Resource Utilization. Statistical analyses were stratified by country; χ test and analysis of covariance were used. Adverse events were monitored. RESULTS: More subjects achieved ACR50 at week 24 with ETN + MTX versus DMARD + MTX (62% vs 23%, respectively), in addition to secondary end points (P < 0.0001 for all); mean change in modified total Sharp score was lower for the ETN + MTX group (0.4 vs 1.4, respectively; P = 0.0270). Improvements in patient-reported outcomes favored ETN + MTX for Health Assessment Questionnaire, 36-item Short-Form, Hospital Anxiety and Depression Scale for depression, WPAI:RA, and Caregiver Burden and Resource Utilization emergency department visits for RA (P < 0.01). Overall, adverse events were similar between the groups (69% vs 68%,); serious adverse events were also similar (4% vs 1%). The rate of overall infections was higher with ETN + MTX (38%) than DMARD + MTX (22%, P ≤ 0.001). CONCLUSIONS: Consistent with published global data among RA patients with inadequate response to MTX, adding ETN to MTX demonstrated better efficacy than adding one other conventional DMARD to MTX. No new safety issues were observed. ETN + MTX provided favorable benefit-risk profile among RA patients from LA region.
23196701 Addition of infliximab compared with addition of sulfasalazine and hydroxychloroquine to m 2013 Dec OBJECTIVE: To compare EuroQol 5-Dimensions (EQ-5D) utility and quality-adjusted life-years (QALYs) in patients with early, methotrexate (MTX) refractory rheumatoid arthritis (RA), randomised to addition of infliximab (IFX) or sulfasalazine and hydroxychloroquine (SSZ+HCQ). METHODS: RA-patients with symptoms <1 year were enrolled between 2002 and 2005 at 15 Swedish centres. After 3-4 months of MTX monotherapy, patients with a remaining DAS28>3.2 were randomised to addition of IFX or SSZ+HCQ and followed for 21 months. EQ-5D profiles were collected every 3 months. Between-group comparisons of utility change and accumulated QALYs were performed, using last observation carried forward (LOCF) following protocol breach. Missing data were imputed by linear interpolation or LOCF. Sensitivity analyses applying baseline observation carried forward (BOCF) or restricted to completers were conducted. RESULTS: Of 487 patients initially enrolled, 128 and 130 were randomised to IFX or SSZ+HCQ, respectively. Mean utility in the IFX and SSZ+HCQ groups increased from 0.52 (SD 0.27) and 0.55 (SD 0.27) at randomisation to 0.66 (SD 0.25) and 0.63 (SD 0.27) at 21 months (adjusted mean difference favouring IFX 0.04; 95% CI -0.01, 0.09; p=0.15). Average accumulated QALYs were 1.10 (SD 0.37) and 1.07 (SD 0.42) in the IFX and SSZ+HCQ groups, respectively (adjusted mean difference favouring IFX 0.07; 95%CI -0.01, 0.14; p=0.07). BOCF analysis showed similar results, while differences were reversed, though remained statistically non-significant among completers. Dropout rates in the IFX/SSZ+HCQ groups were 30%/43% (p=0.01). CONCLUSIONS: Comparing addition of IFX or SSZ+HCQ to MTX in active early RA, no statistically significant differences in utility or QALY gain could be detected over 21 months. TRIAL REGISTRATION: Registered in WHO database at the Karolinska University Hospital, number CT20080004.
23053688 A multicenter, randomized, double-blind clinical trial of combination therapy with Anbainu 2013 Jan This study aims to evaluate the clinical and radiological efficacy as well as safety profiles of Anbainuo, a recombinant human TNFRII:Fc fusion protein, combined with methotrexate (MTX) versus MTX alone or Anbainuo alone in the treatment of Chinese patients with moderate to severe rheumatoid arthritis (RA). In this 24-week, multicenter, double-blind, active comparator-controlled study, 396 RA patients were randomized into combination therapy group (Anbainuo plus MTX), Anbainuo group, or MTX group. Clinical response was assessed using the American College of Rheumatology (ACR)-N, ACR20, ACR50, ACR70, and van der Heijde modification of Sharp score, among which ACR-N and ACR20 were defined as primary major endpoints. After 24 weeks of treatment, the ACR-N in the combination therapy group (12.79 ± 9.24 %) was significantly higher than that in Anbainuo group (9.56 ± 11.16 %) and in MTX group (5.08 ± 11.1 %) (p = 0.00 and p = 0.00, respectively). Patients in Anbainuo group had significantly higher ACR-N than those in MTX group (p = 0.02). More patients in the combination therapy group (53.6 %) achieved ACR50 improvement response than those in the MTX group (30.8 %). ACR70 of combination therapy group (27.7 %) was significantly higher than that of Anbainuo group (15.8 %) and MTX group (7.70 %), with no significant difference between Anbainuo group and MTX group. DAS28-ESR in the combination therapy group was significantly reduced compared to either monotherapy groups. Moreover, DAS28-ESR was significantly lower in Anbainou group than in MTX group. The combination therapy group also showed significantly less radiographic progression than the MTX group (p = 0.03). The total adverse events (AE) in the combination group (40.9 %) was significantly higher than those in the MTX group (28.8 %) (p < 0.05). Anbainuo combined with MTX therapy can effectively control the disease activity and radiographic progression of RA, while the incidence of AE also increased compared to either Anbainuo or MTX.
24095940 Prevalence of comorbidities in rheumatoid arthritis and evaluation of their monitoring: re 2014 Jan BACKGROUND: PATIENTS with rheumatoid arthritis (RA) are at increased risk of developing comorbid conditions. OBJECTIVES: To evaluate the prevalence of comorbidities and compare their management in RA patients from different countries worldwide. STUDY DESIGN: international, cross-sectional. PATIENTS: consecutive RA patients. DATA COLLECTED: demographics, disease characteristics (activity, severity, treatment), comorbidities (cardiovascular, infections, cancer, gastrointestinal, pulmonary, osteoporosis and psychiatric disorders). RESULTS: Of 4586 patients recruited in 17 participating countries, 3920 were analysed (age, 56±13 years; disease duration, 10±9 years (mean±SD); female gender, 82%; DAS28 (Disease Activity Score using 28 joints)-erythrocyte sedimentation rate, 3.7±1.6 (mean±SD); Health Assessment Questionnaire, 1.0±0.7 (mean±SD); past or current methotrexate use, 89%; past or current use of biological agents, 39%. The most frequently associated diseases (past or current) were: depression, 15%; asthma, 6.6%; cardiovascular events (myocardial infarction, stroke), 6%; solid malignancies (excluding basal cell carcinoma), 4.5%; chronic obstructive pulmonary disease, 3.5%. High intercountry variability was observed for both the prevalence of comorbidities and the proportion of subjects complying with recommendations for preventing and managing comorbidities. The systematic evaluation of comorbidities in this study detected abnormalities in vital signs, such as elevated blood pressure in 11.2%, and identified conditions that manifest as laboratory test abnormalities, such as hyperglycaemia in 3.3% and hyperlipidaemia in 8.3%. CONCLUSIONS: Among RA patients, there is a high prevalence of comorbidities and their risk factors. In this multinational sample, variability among countries was wide, not only in prevalence but also in compliance with recommendations for preventing and managing these comorbidities. Systematic measurement of vital signs and laboratory testing detects otherwise unrecognised comorbid conditions.
24023053 Tumor necrosis factor α inhibitor use and decreased risk for incident coronary events in 2014 Mar OBJECTIVE: To determine the association of tumor necrosis factor α (TNFα) inhibitors with risk for cardiovascular disease (CVD) in rheumatoid arthritis (RA) patients. METHODS: A retrospective cohort of 2,101 incident RA patients was established. Medication exposure was categorized into the following groups: TNFα inhibitors alone or in combination with methotrexate (MTX; aTNF group); MTX alone or in combination with other nonbiologic disease-modifying antirheumatic drugs (DMARDs; MTX group); and no MTX, nonbiologic DMARDs (reference group). Primary outcome was adjudicated incident coronary artery disease (CAD), defined as myocardial infarction, unstable angina, or coronary revascularization procedure. Secondary outcome was adjudicated incident CVD, defined as a composite of CAD, stroke, transient ischemic attack, abdominal aortic aneurysm, peripheral arterial disease, or arterial revascularization procedure. Cox regression models were used to calculate the hazard ratio for CAD and CVD for the aTNF and MTX groups compared to the reference group. RESULTS: There were 46 incident CAD and 82 incident CVD events. Adjusting for covariates associated with CAD and CVD, the hazard ratio for incident CAD was 0.45 (95% confidence interval [95% CI] 0.21-0.96) for the aTNF group and 0.54 (95% CI 0.27-1.09) for the MTX group compared to the reference group. Use of TNFα inhibitors for >16.1 months was associated with a relative risk for CAD of 0.18 (95% CI 0.06-0.50) and for CVD of 0.31 (95% CI 0.15-0.65) compared to the reference group. A similar, although not significant, trend was seen with the MTX group. CONCLUSION: Use of TNFα inhibitors is associated with a decreased risk for CAD in RA; the risk decreases further with long-term use. This should be considered when weighing the risks versus benefits of these medications.
24729685 Tocilizumab in the treatment of rheumatoid arthritis and beyond. 2014 Rheumatoid arthritis (RA) is a systemic inflammatory disease characterized by joint pain, swelling, stiffness, and progressive destruction of the small joints of the hands and feet. Treatment of RA has improved over the past decade. With multiple cytokines well-known now to play a role in the pathogenesis of RA, including tumor necrosis factor alpha, interleukin (IL)-1β, and IL-6, many targeted biological treatments against these cytokines have emerged, changing the treatment of this disease. Tocilizumab (TCZ) is a recombinant humanized monoclonal antibody against the IL-6 receptor and has been approved in many countries, including the United States, for the treatment of moderate to severe RA in patients who have not adequately responded to one or more disease-modifying antirheumatic drugs (DMARDs) or cannot tolerate other approved drug classes for RA. The aim of this review is to discuss the role of IL-6 in RA, and to provide an overview of the mode of action, pharmacokinetics, and safety of TCZ. Furthermore, efficacy studies of TCZ as both monotherapy and combination therapy will be evaluated. There have been several important clinical trials evaluating the efficacy and safety of TCZ in RA patients; this review summarizes this data from 14 key trials with emphasis on Phase III trials. Review of these trials provides strong evidence that its use, both as monotherapy and in combination with methotrexate or other DMARDs, is an effective treatment in reducing the signs and symptoms of RA. TCZ showed tolerable safety but care is required for its use since there are some important safety concerns including elevated liver enzymes, elevated low-density lipoprotein, infections, and gastrointestinal perforations. Additionally, given the efficacy of TCZ in the treatment of RA, this review discusses how TCZ may be beneficial in the treatment of other autoimmune diseases, spinal disease, cardiovascular disease, organ transplantation, and malignancies where elevated levels of IL-6 may play a role in the pathogenesis of these diseases.
23463543 Changes in use of disease-modifying antirheumatic drugs for rheumatoid arthritis in the Un 2013 Sep OBJECTIVE: Use of nonbiologic disease-modifying antirheumatic drugs (DMARDs) and/or biologic DMARDs is generally recommended to improve the prognosis of patients with rheumatoid arthritis (RA). The objective of this study was to describe the changing trends in DMARD use for RA over the past 2 decades. METHODS: We analyzed data from an open longitudinal cohort of RA patients recruited from rheumatologists' practices in northern California. We examined baseline demographic and clinical characteristics of the participants and their long-term DMARD use through annual comprehensive structured telephone interviews. RESULTS: A total of 1,507 established RA patients were recruited through 5 enrollment periods between 1983 and 2009. Between 1983 and 2009, the use of any DMARD increased from 71% of all patients to 83% (P for trend < 0.0001). In 2009, 43% received a biologic DMARD, 34% were on both nonbiologic and biologic DMARDs, and 40% were treated with only nonbiologic DMARDs. The 4 most commonly used nonbiologic DMARDs in 2009 were methotrexate (49%), hydroxychloroquine (30%), leflunomide (13%), and sulfasalazine (7%). Etanercept (20%) was the most commonly used biologic DMARD in 2009, followed by infliximab (10%), adalimumab (9%), and abatacept (6%). Use of oral steroids was common (40-50%) and remained similar throughout the study period. CONCLUSION: There has been a significant increase in the use of DMARDs for RA over the past 2 decades. However, 15% of the individuals with a clinical diagnosis of RA were not receiving DMARDs in 2009. Future research should focus on sociodemographic and clinical factors associated with DMARD use for RA.
24382276 Perceptions of methotrexate use in rheumatoid arthritis by rheumatologists and their patie 2013 Dec AIM: To improve treatment for rheumatoid arthritis (RA), rheumatologists have embraced patient-reported outcomes; however, limited data are available on patient perceptions of treatment. Our objective was to assess the use and perceptions of methotrexate (MTX) by patients with RA (primary objective) and their rheumatologists, patient-reported adverse events (AEs) related to MTX, and patient-reported use of alcohol, folic acid and biologic agents. METHOD: Each rheumatologist completed a rheumatologist questionnaire and then asked patients with RA to complete a patient questionnaire. RESULTS: Questionnaires were completed by 46/50 rheumatologists and 1313/1313 patients. Patients (72% female, 38% > 10 years RA) took oral MTX regularly (72% never miss a dose) and at therapeutic doses. Most patients (79%) were currently taking MTX, but 36% of patients were on low doses (≤ 10 mg/week) and 8% intentionally and regularly did not take MTX. Most patients had a positive perception of MTX; 82% of patients considered MTX to be important; 60% preferred to continue taking MTX. Although AEs (generally mild and gastrointestinal) occurred regularly (38%) and in some patients continuously (13%), 41% of patients did not experience an AE. Patients abstained from alcohol (46%) and took folic acid (91%, but with variable dosage regimens and doses). There were 29% of patients taking biologic agent therapy; only 70% of these patients were also taking MTX. CONCLUSION: MTX was well used, well tolerated and well perceived. However, to ensure that MTX therapy is as effective as possible, rheumatologists should discuss MTX use with their patients and consider alternative strategies for some patients.
23905378 [Treating rheumatoid arthritis patients of Shen deficiency and cold invading syndrome by b 2013 May OBJECTIVE: To evaluate the clinical efficacy and safety of bushen quhan zhiwang decoction (BQZD) combined methotrexate (MTX) in treating rheumatoid arthritis (RA). METHODS: A prospective, randomized controlled study was carried out. RA patients of Shen deficiency and cold invading syndrome in the treatment group (120 cases) were treated with BQZD and MTX (10 mg/week), while those in the control group (120 cases) were treated with MTX (10 mg/week) alone. The therapeutic course for all was 24 weeks. The efficacy and safety indices were evaluated at the baseline and 24 weeks after treatment, including clinical signs and symptoms, condition assessment, Health Assessment Questionnaire (HAQ), disease activity index 28 (DAS28), laboratory parameters of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), safety indicators, and Chinese medical syndrome integrals. RESULTS: The total effective rate was 80. 0% in the treatment group, better than that of the control group (66.7%), showing statistical difference (P <0.01). In the two groups significant improvement of clinical signs and symptoms, ESR, CRP, visual analogue scale (VAS) by both physicians and patients, HAQ, DAS28, and Chinese medical syndrome integrals after treatment were shown (P <0.01). Better effects were obtained in the treatment group in lessening tender joint numbers and swollen joint numbers, VAS by both physicians and patients, DAS28, and Chinese medical syndrome integrals (P < 0.05). Besides, adverse reactions occurred less in the treatment group than in the control group (P < 0.05). CONCLUSIONS: BQZD had roles in relieving symptoms, improving joint functions, signs, ESR, and CRP. It was an effective herb for RA patients of Shen deficiency and cold invading syndrome. It could enhance the efficacy and reduce adverse reactions of MTX through synergistic effects with MTX.
24006307 Evaluation of therapeutic efficacy of Majoon Suranjan, a Unani formulation, in the treatme 2013 Dec Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder. Allopathic treatments for RA have various side-effects and limitations. Majoon Suranjan (MS) is a polyherbal Unani formulation used to treat RA. Although it is widely used, evidence-based toxicity and efficacy data are not available. The present study was designed to assess the safety and therapeutic efficacy of MS in experimental animals. Acute (14 days) and long-term (90 days) toxicity studies were carried out at three doses of MS, i.e. 440, 880 and 1760 mg/kg body weight in male and female Wistar rats. Arthritis was induced in male rats by immunization with bovine collagen type II and they were treated with vehicle, methotrexate (0.25 mg/kg body weight, intraperitoneal once weekly) and MS (880 mg/kg body weight, orally, daily) for 20 days. Serum rheumatoid factor, anticyclic citrullinated peptide antibody, antinuclear antibody and C-reactive protein (CRP) were estimated. None of the rats exhibited overt toxicity or mortality and MS was found to be safe at the tested doses. No abnormal findings were observed in haematological and biochemical parameters, necropsy and histopathology at therapeutic effective dose. MS significantly inhibited the footpad swelling in arthritic rats while serum autoantibodies and CRP levels were significantly decreased. The present study demonstrates that at therapeutic doses, the Unani medicine, MS is relatively safe. Furthermore, MS was found to be effective in decreasing the biomarkers of RA, thus providing scientific evidence in support of its traditional use in the treatment of RA.
25451821 [Monitoring the functional capacity of patients with rheumatoid arthritis for three years] 2015 Jan OBJECTIVE: To quantify modification of functional capacity in a three year period in a group of patients with rheumatoid arthritis (RA) using HAQ and EPM-ROM inventories. METHODS: Forty patients with RA on methotrexate (MTX) as disease-modifying anti rheumatic drug (DMARD) were followed for up to three years. The functional status was assessed at the beginning and end of the period by HAQ and EPM-ROM. RESULTS: Thirty two patients were retrieved, with initial HAQ score of 1.14±0.49 (mean±SD) and EPM-ROM score of 5.8±2.75. After an average period of three years, the HAQ score was 1.13±0.49 and EPM-ROM score, 6.81±3.66. In the subgroup of seven patients submitted to orthopedic surgery, HAQ score decreased from 0.84±0.72 to 1.64±0.56 and the EPM-ROM score, from 5.8±1.80 to 8.3±0.74. In the subgroup of non-operated patients, HAQ score varied from of 1.2±0.45 to 1.07±0.70 and EPM-ROM score, from 5.7±3.06 to 6.4±3.90. CONCLUSION: In a group of RA patients in use of only MTX as DMARD, there was little change on HAQ score and EPM-ROM scores over the average period of three years. Worsening functional capacity was observed in the group of operated patients in comparison to the not operated ones. This fact alerts us to the need for use of broader therapeutic regimens availability of musculoskeletal surgeries in a timely manner in patients with RA.
25608624 The supplementary therapeutic DMARD role of low-dose glucocorticoids in rheumatoid arthrit 2014 Nov 13 The management of rheumatoid arthritis (RA) is primarily based on the use of disease-modifying antirheumatic drugs (DMARDs), mainly comprising synthetic chemical compounds (that is, methotrexate or leflunomide) and biological agents (tumor necrosis factor inhibitors or abatacept). On the other hand, glucocorticoids (GCs), used for decades in the treatment of RA, are effective in relieving signs and symptoms of the disease, but also interfere with radiographic progression, either as monotherapy or in combination with conventional synthetic DMARDs. GCs exert most of their biological effects through a genomic action, using the cytosolic GC receptor and then interacting with the target genes within target cells that can result in increased expression of regulatory--including anti-inflammatory--proteins (transactivation) or decreased production of proinflammatory proteins (transrepression). An inadequate secretion of GCs from the adrenal gland, in relation to stress and inflammation, seems to play an important role in the pathogenesis and disease progression of RA. At present there is clear evidence that GC therapy, especially long-term low-dose treatment, slows radiographic progression by at least 50% when given to patients with early RA, hence satisfying the conventional definition of a DMARD. In addition, long-term follow-up studies suggest that RA treatment strategies which include GC therapy may favorably alter the disease course even after their discontinuation. Finally, a low-dose, modified night-release formulation of prednisone, although administered in the evening (replacement therapy), has been developed to counteract the circadian (night) rise in proinflammatory cytokine levels that contributes to disease activity, and might represent the way to further optimize the DMARD activity exerted by GCs in RA.
22807272 Racial/ethnic differences in the use of biologic disease-modifying antirheumatic drugs amo 2013 Feb OBJECTIVE: To assess racial/ethnic differences in the use of biologic disease-modifying antirheumatic drugs (DMARDs) among California Medicaid (Medi-Cal) rheumatoid arthritis (RA) patients. METHODS: Medi-Cal patient level data for 5,385 DMARD recipients between ages 18 and 100 years with at least 1 diagnosis of RA (International Classification of Disease, Ninth Revision, Clinical Modification code 714.xx) and the use of 1 DMARD between January 1, 1998 and December 31, 2005 were collected. The outcome of interest was the choice of either standard DMARDs (methotrexate, lefluonomide, hydroxychloroquine, and sulfasalazine) or biologic DMARDs (adalimumab, etanercept, anakinra, and infliximab). A univariate analysis and logistic regression model were applied to examine the association of the choice of DMARD among different racial/ethnic groups. RESULTS: In the univariate analysis, biologic DMARD use was significantly associated with race/ethnicity (P < 0.001). In the multivariate logistic regression model, after adjusting for age, sex, insurance coverage, 12 comorbid conditions, RA-related drug prescription, RA-related inpatient stay, and rehabilitation visits, African Americans had 53% lower odds of receiving biologic DMARDs as compared to whites, whereas Hispanics had 36% increased odds of receiving biologic DMARDs as compared to whites. CONCLUSION: In this Medi-Cal population, with its racial diversity and relatively homogenous socioeconomic status and health care benefits, racial/ethnic differences were found in RA patients receiving biologic DMARDs.
22212411 Immunohistological analysis of synovium treated with abatacept in rheumatoid arthritis. 2013 Jul The aim of this study was to investigate the histological changes following the treatment with abatacept compared with methotrexate (MTX) by an immunohistological examination of synovial tissue for eleven different molecules to detect the expression patterns of cytokines. We histologically assessed the synovial tissues from 10 methotrexate (MTX)-treated RA patients as controls and 5 abatacept plus MTX-treated RA patients. The synovium samples from both group were assessed by hematoxylin and eosin (HE) staining and analyzed for their expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), matrix metalloproteinase-3 (MMP-3), CD20, CD68, vascular endothelial growth factor (VEGF), CD4, CD8, CD28, CD80, and CD86 by an immunohistological examination. HE staining showed that there was a decrease in cell proliferation in the synovium of the RA patients who received abatacept compared with the controls. TNF-α, IL-6, and VEGF were not significantly different in either of the groups. On the other hand, MMP-3, CD68, CD4, CD8, CD20, CD80, and CD86 were significantly decreased in the abatacept group compared with the control (P < 0.05). Based on the histological analysis of the synovium, it appears that the efficacy of the treatment with abatacept may involve the inhibition of cell proliferation, with decreases in the expression of MMP-3, CD68, CD4, CD8, CD20, CD80, and CD86 in the synovium. These findings indicate inhibition of not only T cells but also B cells and macrophages, which likely plays a role in the efficacy of abatacept in RA patients.
25036562 Nearly pain-free self-administration of subcutaneous methotrexate with an autoinjector: re 2014 Aug BACKGROUND: A methotrexate autoinjector (MTXAI) was developed for self-administration of subcutaneous (SC) methotrexate by patients with rheumatoid arthritis (RA). The MTXAI circumvents the need for vials, needles, and syringes and may therefore improve dosing accuracy, handling risks, and patient adherence. OBJECTIVES: The objective of this study was to evaluate actual human use of the MTXAI in patients with RA and determine its reliability, robustness, safety, local tolerance, and ease of use. METHODS: In this phase 2, multicenter, open-label, single-dose, single-arm, in-clinic US study, adults (N = 101) treated with methotrexate for 3 months or longer were trained to use the MTXAI and assigned to 10, 15, 20, or 25 mg methotrexate based on previous treatment and disease status. Patients completed training confirmation and ease-of-use questionnaires. Pain was evaluated immediately after self-administration and at follow-up with a 100-mm visual analog scale (0 = no pain, 100 = worst possible pain). RESULTS: At screening, 90.1% of patients had moderate to severe functional limitations (class II-IV). All patients successfully completed the study. All devices functioned correctly and as intended. The device was rated easy to use by 98%, and instructions clear and easy to follow by 100% of patients. On the visual analog scale, mean and median pain scores were 3.6/100 and 1.0/100 mm, respectively, immediately after self-administration, and were lower at follow-up. Most patients (92.3%) had no administration-site erythema; 7.7% had minimal erythema. CONCLUSIONS: The SC MTXAI was well tolerated and considered easy to use by patients with RA. Improving SC methotrexate delivery may increase patient tolerance of self-administration, possibly improving adherence.
24237999 Remission in rheumatoid arthritis patients treated with etanercept monotherapy: clinical p 2013 Nov OBJECTIVES: To assess, in a randomised controlled trial (RCT) and in clinical practice, an association of time to remission and baseline disease activity with both induction of remission and sustained remission in etanercept-treated patients with rheumatoid arthritis (RA). METHODS: Data from an RCT (Trial of Etanercept and Methotrexate with Radiographic Patient Outcomes [TEMPO]; n=682) and an observational registry (Rheumatoid Arthritis DMARD Intervention and Utilization Study [RADIUS II]; n=4341) were used to evaluate disease activity (Clinical Disease Activity Index [CDAI] score) over time in patients initiating etanercept (monotherapy or with methotrexate). CDAI remission (CDAI≤2.8) and sustained remission (≥6 months) were determined through year 3 by treatment group, study, time to remission, and disease severity. RESULTS: Patients from TEMPO and RADIUS II who received etanercept monotherapy showed similar CDAI remission rates (39% and 35%, respectively, at 3 years). Among patients who received etanercept with methotrexate, remission rates were 54% and 36%, respectively. Remission occurred more rapidly in TEMPO than RADIUS II perhaps from differences in compliance, patient populations, or sequence of combination therapy initiation. Generally, more patients with lower baseline CDAI scores achieved remission than those with higher scores. Continued remission appeared more likely in patients achieving remission earlier in the course of their therapy (0-6 months). CONCLUSIONS: Remission by year 3 in etanercept-treated (with and without methotrexate) patients with RA occurred in ≥35% of patients in both an RCT (TEMPO) and a clinical practice setting (RADIUS II), and more frequently in those with lower baseline disease severity. Patients with lower RA disease activity were more likely to reach remission. Continued remission may be more likely in patients who achieved remission earlier.
24620636 Effects of adalimumab administration in bio-naïve and bio-switch rheumatoid arthritis pat 2013 Nov AIMS: To investigate the impact of adalimumab on the biologic-naive (bio-naïve) and bio-switch rheumatoid arthritis (RA) patients, and to clarify the appropriate indications for adalimumab treatment. METHODS: The retention rate, efficacy and safety of adalimumab in twenty-one RA patients were analyzed. Fourteen of the patients were bio-naive and seven were bio-switched from other biologics. Concomitant methotrexate was used in 85% of the bio-naive and 71% of the bio-switch patients. The radiographic findings before and after the 1 year and the two years treatment were also surveyed. RESULTS: In the bio-naive group, 63% of patients continued adalimumab for 2 years, and remission was achieved in approximately 50% of patients. The mean 28-joint Disease Activity Scores improved from 5.2 to 2.6. Radiographically, the joint damage did not progress in either erosions or joint space narrowing. In the bio-switch group, the retention rate was 29%, and only patients who were switched from infliximab showed responses to the treatment. Herpes zoster requiring hospitalization occurred in two cases and injection site reactions were noted in other two cases. CONCLUSION: Adalimumab combined with methotrexate would be a useful first choice biologic regimen in bio-naïve RA patients. As a second biologic, adalimumab could be useful only when treatments are switched from infliximab.