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ID PMID Title PublicationDate abstract
25227967 Initial high-dose prednisolone combination therapy using COBRA and COBRA-light in early rh 2015 Treatment with initial high-dose prednisolone and a combination of methotrexate (MTX) and sulfasalazine (SSZ) according to the COBRA regimen (Dutch acronym for combinatietherapie bij reumatoide artritis, 'combination therapy for rheumatoid arthritis'), has repeatedly been demonstrated to be very effective in early rheumatoid arthritis (RA). COBRA combination therapy is superior to initial monotherapy of SSZ and MTX, is also associated with a good long-term outcome, is as safe as other treatment regimes, and performs as well as the combination of high-dose MTX and the tumor necrosis factor antagonist infliximab. A pilot study with an intensified version of the COBRA combination therapy showed that strict monitoring and aggressive treatment intensification based on the Disease Activity Score can result in a remission rate of 90% in patients with active early RA. Also, the first results indicate that an attenuated variation on COBRA combination therapy, called 'COBRA-light', is effective in decreasing disease activity and is generally well tolerated. Based on these results, we conclude that initial high-dose prednisolone in combination with MTX and SSZ could or should be the first choice in early active RA since it is effective and safe, and the cost price of the drugs is low.
22807253 Increase of body mass index in a tight controlled methotrexate-based strategy with prednis 2013 Jan OBJECTIVE: To clarify whether increase of body weight in patients with early rheumatoid arthritis (RA) upon administration of prednisone is a side effect of prednisone or a result of better control of disease activity, we examined the association of prednisone and disease activity with a subsequent change in body mass index (BMI). METHODS: In the Computer Assisted Management in Early Rheumatoid Arthritis Trial-II, patients ages ≥18 years with early RA (disease duration <1 year and no prior use of disease-modifying antirheumatic drugs) had been randomized to a methotrexate (MTX)-based tight control strategy with either 10 mg of prednisone (MTX + prednisone) or placebo (MTX + placebo). The MTX + prednisone group had lower disease activity, but gained more weight than the MTX + placebo group (mean ± SD 2.9 ± 4.2 kg versus 1.3 ± 5.3 kg; P = 0.03). Data from patients with monthly measurements of disease activity (Disease Activity Score in 28 joints [DAS28]) and BMI were analyzed with a longitudinal regression (mixed model) analysis with BMI as the dependent variable and treatment strategy and DAS28 as the independent variables, correcting for baseline BMI and possible confounders (sex, age, and rheumatoid factor status). RESULTS: There was no independent association of glucocorticoid therapy with a change in BMI, but a lower DAS28 was associated with an increased BMI 6 months later. The association of the DAS28 with BMI was most strongly present in postmenopausal women. Clinical cutoff points showed a clear association between DAS28 level and the change in BMI 6 months later. CONCLUSION: Weight gain during treatment with prednisone seems attributable to a reduction of disease activity and is probably, at least partly, regained weight.
24614280 Rheumatoid arthritis medications and lactation. 2014 May PURPOSE OF REVIEW: In contrast to the disease remission enjoyed by a majority of rheumatoid arthritis (RA) patients during pregnancy, the immediate postpartum period is generally characterized by flare. Managing symptoms during this time is challenging because the potential transfer of medication into the breast milk of nursing mothers may limit which antirheumatic drugs can be safely used. The benefits of breastfeeding are significant, however, so an understanding of how to adjust medications to permit lactation and nursing is important for rheumatologists. RECENT FINDINGS: Although nonsteroidal antiinflammatory drugs (NSAIDs) in general are passed into milk in low doses, shorter acting NSAIDs are preferred, with caution for premature infants. Prednisone can be taken by nursing mothers, although when used at doses higher than 20 mg/day an interval of 4 h after dosing and prior to breastfeeding is recommended. Hydroxychloroquine and sulfasalazine are compatible with nursing. Cyclosporine is generally allowed in lactating women, although a single infant was reported to develop therapeutic drug levels. Azathioprine (AZA) and tissue necrosis factor-α-inhibitors have little to no transfer into breast milk, with negligible levels measured in infant sera, and thus may be considered for use in lactating mothers. Methotrexate and leflunomide should not be used. Other biological RA medications have not been evaluated, and are, therefore, best avoided by breastfeeding patients. SUMMARY: Many but not all RA medications may be used during lactation with low risk to the nursing infant; this review summarizes the available data for commonly used medications in order to help guide therapy during the postpartum period.
24517052 [Treatment of rheumatoid arthritis by xinfeng capsule: an efficacy observation]. 2013 Dec OBJECTIVE: To observe the curative effect of Xinfeng Capsule (XC) in treatment of rheumatoid arthritis (RA). METHODS: Recruited were 80 active RA patients, who were randomly assigned to the normal control group and the treatment group, 40 in each group. All patients received the same routine anti-rheumatic treatment: Methotrexate 10 mg per week; Diclofenac 50 mg when pain was obvious, twice daily. Patients in the treatment group took XC 3 tablets each time, thrice daily. All treatment lasted for 12 consecutive weeks. Serum iron (SI), serum ferritin (SF), transferrin (TRF); and RA disease activity index (DAS-28) were detected in all patients. RESULTS: XC could improve HAQ, DAS-28, hypersensitive C reactive protein (hs-CRP), prostaglandins A (PGA), erythrocyte sedimentation rate (ESR), number of swelling joints, number of tender joints, and morning stiffness time in acute RA patients, showing statistical difference when compared with those of the control group (P < 0.01, P < 0.05). Compared with the control group, SI, SF, DAS-28, and TRF significantly decreased in the treatment group (P < 0.05). CONCLUSION: XC could improve DAS-28, and SI reserve in patients with active RA, and lower DAS-28 related indicators.
22975732 Efficacy of adjunct tacrolimus treatment in patients with rheumatoid arthritis with inadeq 2013 Jul OBJECTIVES: We aimed to assess the efficacy of tacrolimus (TAC) as an add-on therapy in patients with rheumatoid arthritis (RA) who were previously treated with methotrexate (MTX) but not with biologics. METHODS: The study group (MTX + TAC group) consisted of 157 patients (selected from among the patients in the Institute of Rheumatology, Rheumatoid Arthritis [IORRA] RA cohort from April 2005 to October 2009) who received add-on therapy with TAC in addition to MTX, but without biologics. A propensity score (PS) for the use of TAC was derived, and 471 PS-matched patients who received MTX alone or MTX with other non-biologic disease-modifying antirheumatic drugs (except for TAC), but not with biologics, were selected and served as the control group. Changes in disease activity in the two groups during three consecutive IORRA phases were analyzed by adjusting for confounding factors. RESULTS: The median 28-joint disease activity score (DAS28) decreased from 4.58 to 3.70 in the MTX + TAC group and from 4.12 to 3.61 in the control group. After adjusting for confounding factors, the decrease in the DAS28 score in the MTX + TAC group was significantly larger (by 0.273 points) than that in the control group (P < 0.05). CONCLUSION: This study demonstrated the efficacy of add-on therapy with TAC to MTX in patients with RA in daily practice.
24962606 Etanercept-associated transient bone marrow aplasia: a review of the literature and pathog 2014 Jun A patient with rheumatoid arthritis presented with increasing fatigue, fever, gingival bleeding, and petechial rash. Her symptoms started 1 week after the first injection of etanercept (Enbrel). Her only other medications (methotrexate and hydroxychloroquine) had been unchanged for years. Tests revealed severe pancytopenia and bone marrow aplasia. She recovered with supportive treatment within 12 days. The literature on serious blood dyscrasias associated with anti-tumor necrosis factor-α therapy is reviewed, an intriguing postulated mechanism is discussed, and selective patient monitoring is recommended.
23668332 Safety evaluation of leflunomide in rheumatoid arthritis. 2013 Jul INTRODUCTION: Leflunomide is a prodrug which is rapidly converted following oral administration and absorption to an active metabolite with anti-proliferative effects (A77 1726/teriflunomide). Leflunomide was developed as an immunomodulatory agent and subsequently developed as a disease-modifying anti-rheumatic drug (DMARD) for the management of rheumatoid arthritis (RA). AREAS COVERED: This review article covers the mechanism of action of the drug, clinical indications, including efficacy data from clinical trials, safety data from clinical trials, post marketing studies and surveillance databases and safety in special populations. Additionally, the review discusses the current place of leflunomide in the management of RA, and its likely future as an anti-rheumatic drug. EXPERT OPINION: Leflunomide is a relatively safe drug, with proven efficacy in RA management. Its clinical use is limited by the historic parallel development of other agents, including methotrexate, which has become the synthetic DMARD of choice and biological DMARDs that have superior efficacy.
23729804 Sustained clinical remission and rate of relapse after tocilizumab withdrawal in patients 2013 Jul OBJECTIVE: Data on when to stop use of biological agents in rheumatoid arthritis (RA) are scant. We assessed the length of remission and the rate of clinical relapse in patients with RA who had to discontinue treatment with tocilizumab (TCZ) because of the ending of longterm (5 yrs) open-label clinical trials. METHODS: All patients at 2 participating centers in Mexico were in remission, defined as Disease Activity Score 28 ≤ 2.6, with no swollen joints at the time of the last TCZ infusion. Patients were followed thereafter every 8 weeks for 12 months or until relapse. Relapse was defined as the presence of ≥ 1 swollen joint. Doses of methotrexate and antiinflammatory drugs were not changed during the followup period. RESULTS: Forty-five patients were analyzed, 87% were women (mean age 52 yrs, mean disease duration 14 yrs). During the 12 months of followup, 44% of patients maintained remission. Relapses occurred in 56% of patients: 14 during the first 3 months after the last TCZ administration. Retreatment using other agents achieved low disease activity or remission. CONCLUSION: Longterm clinical remission is possible in a number of patients with RA after suspension of TCZ. This effect has also been reported with other biologic agents. Additional data are required to support recommendations for discontinuing a biological agent after achieving remission.
24344049 Combination of Mangifera indica L. extract supplementation plus methotrexate in rheumatoid 2014 Aug The purpose of the present study was to evaluate the possible therapeutic effects and the safety of Mangifera indica extract (Vimang tablets, 300 mg) combined with methotrexate (MTX) on reducing disease activity in rheumatoid arthritis (RA). Twenty patients with active RA underwent a year of treatment with MTX (12.5 mg/week) associated to non-steroidal anti-inflammatory drugs (NSAIDs) and/or prednisone (5-10 mg/day) were randomly allocated to the experimental group (n=10), that received the extract supplementation (900 mg/day) or preceding usual treatment (n=10) during 180 days. RA activity was evaluated using the tender and swollen joint counts, erythrocyte sedimentation rate, disease activity score-28 (DAS 28), visual analogue scale (VAS) and health assessment questionnaire (HAQ). Treatment's efficacy was demonstrated with ACR criteria. Only the patients of MTX-Vimang group revealed statistically significant improvement in DAS 28 parameters with respect baseline data but no differences were observed between groups. ACR improvements amounted 80% only in MTX-Vimang group at the 90 days (p<0.001). In MTX-Vimang group, 100% of patients decreased NSAIDs administration (p<0.01) and 70% of those eradicated gastrointestinal side effects (p<0.01) ensuing of the preceding treatment. Other adverse effects were not reported.
23912798 Remission induction comparing infliximab and high-dose intravenous steroid, followed by tr 2014 Jan OBJECTIVES: In disease modifying antirheumatic drug (DMARD)-naive early rheumatoid arthritis (RA), to compare the efficacy of methotrexate (MTX) and infliximab (IFX) with MTX and intravenous corticosteroid for remission induction. METHODS: In a 78-week multicentre randomised controlled trial, double-blinded to week 26, 112 treatment-naive RA patients (1987 American College of Rheumatology classification criteria) with disease activity score 44 (DAS44)>2.4 were randomised to MTX + IFX or MTX + single dose intravenous methylprednisolone 250 mg. A treat-to-target approach was used with treatment escalation if DAS44>2.4. In the IFX group, IFX was discontinued for sustained remission (DAS44<1.6 for 6 months). The primary outcome was change in modified total Sharp-van der Heijde score (mTSS) at week 50. RESULTS: The mean changes in mTSS score at week 50 in the IFX and intravenous steroid groups were 1.20 units and 2.81 units, respectively (adjusted difference (95% CI) -1.45 (-3.35 to 0.45); p=0.132). Radiographic non-progression (mTSS<2.0) occurred in 81% vs 71% (OR 1.77 (0.56 to 5.61); p=0.328). DAS44 remission was achieved at week 50 in 49% and 36% (OR 2.13 (0.91 to 5.00); p=0.082), and at week 78 in 48% and 50% (OR 1.12 (0.47 to 2.68); p=0.792). Exploratory analyses suggested higher DAS28 remission at week 6 and less ultrasound synovitis at week 50 in the IFX group. Of the IFX group, 25% (14/55) achieved sustained remission and stopped IFX. No substantive differences in adverse events were seen. CONCLUSIONS: In DMARD-naive early RA patients, initial therapy with MTX+high-dose intravenous steroid resulted in good disease control with little structural damage. MTX+IFX was not statistically superior to MTX+intravenous steroid when combined with a treat-to-target approach.
24316899 Adalimumab in rheumatoid arthritis treatment: a systematic review and meta-analysis of ran 2013 Sep Since the discovery of the role of tumor necrosis factor in the physiopathological process of rheumatoid arthritis, five drugs that block this cytokine have been used as therapeutic options. To evaluate the efficacy and safety of adalimumab in the treatment of rheumatoid arthritis we performed a systematic review and meta-analysis of randomized controlled trials. A search of relevant studies in Medline (through PubMed) and LILACS in June 2011 was carried out. Study selection, data collection and analysis were performed in pairs and independently by two reviewers and by a third reviewer in cases of disagreement. The meta-analysis was performed using the software Review Manager® 5.1 using the random effects model. Eleven articles related to adalimumab were included and considered nine studies with 3461 patients. Ten studies showed low risk of bias regarding the blinding of participants and personnel and blinding of outcome assessment. Patients who received the combination treatment of adalimumab and methotrexate showed better efficacy results and lower radiographic progression when compared to placebo + methotrexate in 24-104 weeks. Patients who received adalimumab as monotherapy showed better efficacy outcomes when compared to placebo in 24 and 26 weeks. The results of the meta-analyses of adverse events were not statistically significant, except for reactions at the injection site, which favored the control group. Adalimumab efficacy was demonstrated in monotherapy and when associated to a DMARD, but the evidence for combined use is more robust.
24673659 Prediction of antiarthritic drug efficacies by monitoring active matrix metalloproteinase- 2014 May 5 Active matrix metalloproteinase-3 (MMP-3) is a prognostic marker of rheumatoid arthritis (RA). We recently developed an MMP-3 probe that can specifically detect the active form of MMP-3. The aim of this study was to investigate whether detection and monitoring of active MMP-3 could be useful to predict therapeutic drug responses in a collagen-induced arthritis (CIA) model. During the period of treatment with drugs such as methotrexate (MTX) or infliximab (IFX), MMP-3 mRNA and protein levels were correlated with fluorescence signals in arthritic joint tissues and in the serum of CIA mice. Also, bone volume density and erosion in the knee joints and the paws of CIA mice were measured with microcomputed tomography (micro-CT), X-ray, and histology to confirm drug responses. In joint tissues and serum of CIA mice, strong fluorescence signals induced by the action of active MMP-3 were significantly decreased when drugs were applied. The decrease in RA scores in drug-treated CIA mice led to fluorescence reductions, mainly as a result of down-regulation of MMP-3 mRNA or protein. The micro-CT, X-ray, and histology results clearly showed marked decreases in bone and cartilage destruction, which were consistent with the reduction of fluorescence by down-regulation of active MMP-3 in drug-treated CIA mice. We suggest that the MMP-3 diagnostic kit could be used to detect and monitor the active form of MMP-3 in CIA mice serum during a treatment course and thereby used to predict the drug response or resistance to RA therapies at an earlier stage. We hope that monitoring of active MMP-3 levels in arthritis patients using the MMP-3 diagnostic kit will be a promising tool for drug discovery, drug development, and monitoring of drug responses in RA therapy.
25477167 Upconversion nanoprobes for efficiently in vitro imaging reactive oxygen species and in  2015 Jan Over-generation of reactive oxygen species (ROS) is closely associated with the biological processes of rheumatoid arthritis (RA). Thus, efficient monitoring ROS in inflammatory joints would be essential for better understanding the pathogenesis and optimizing therapeutic interventions. Herein, we designed a ratiometric nanoprobe utilizing upconversion nanoparticles (UCNPs) conjugated with chromophore labeled hyaluronic acid (HA) for high sensitively sensing ROS in the aqueous solution, bioimaging ROS in inflammatory mimic cells and diagnosing RA in vivo. In this approach, the conjugation of HA conferred UCNPs not only water solubility but also biocompatibility and ROS recognizing properties. Particularly, the HA backbone cleavage and detachment of chromophore labeled HA fragments from UCNPs induced by ROS inhibited the luminescent energy transfer (LRET) and allowed rational metric upconversion luminescence (UCL) emission as the detection signal. Importantly, the upconversion nanoprobe showed high effectiveness for early assessing the treatment response of arthritic animals to an antiarthritic drug-methotrexate (MTX).
23908187 Targeted treatment with a combination of traditional DMARDs produces excellent clinical an 2014 Nov OBJECTIVE: To study whether adding initial infliximab to remission-targeted initial combination-DMARD treatment improves the long-term outcomes in patients with early rheumatoid arthritis (RA). METHODS: Ninety-nine patients with early, DMARD-naïve RA were treated with a triple combination of DMARDs, starting with methotrexate (max 25 mg/week), sulfasalazine (max 2 g/day), hydroxychloroquine (35 mg/kg/week), and with prednisolone (7.5 mg/day), and randomised to double blindly receive either infliximab (3 mg/kg; FIN-RACo+INFL) or placebo (FIN-RACo+PLA) infusions during the first 6 months. After 2 years the treatment strategies became unrestricted, but the treatment goal was strict ACR remission. At 5 years the clinical and radiographic outcomes were assessed. RESULTS: Ninety-one patients (92%) were followed up to 5 years, 45 in the FIN-RACo+INFL and 46 in the FIN-RACo+PLA groups. At 5 years, the respective proportions of patients in strict ACR and in disease activity score 28 remissions in the FIN-RACo+INFL and FIN-RACo+PLA groups were 60% (95% CI 44% to 74%) and 61% (95% CI 45% to 75%) (p=0.87), and 84% (95% CI 71% to 94%) and 89% (95% CI 76% to 96%) (p=0.51). The corresponding mean (SD) total Sharp/van der Heijde scores at 5 years were 4.3 (7.6), and 5.3 (7.3), while the respective mean Sharp/van der Heijde scores changes from baseline to 5 years were 1.6 (95% CI 0.0 to 3.4) and 3.7 (95% CI 2.2 to 5.8) (p=0.13). CONCLUSIONS: In early RA, targeted treatment with a combination of traditional DMARDs and prednisolone induces remission and minimises radiographic progression in most patients up to 5 years; adding initial infliximab for 6 months does not improve these outcomes.
25228126 Glucocorticoids in early rheumatoid arthritis: are the benefits of joint-sparing effects o 2015 This paper reviews the clinical effects on bone of 10 mg of prednisone daily in early rheumatoid arthritis, given for 2 years in the Utrecht Study and in the second CAMERA (Computer- Assisted Management in Early Rheumatoid Arthritis) Study, and addresses the question whether there were joint-sparing effects and whether these were offset by adverse effects, especially osteoporosis. We conclude that a 2-year adjunct treatment with 10 mg of prednisone daily increases the benefits of disease-modifying antirheumatic drug therapy and has joint-sparing properties, even if added to the tight control methotrexate-based strategy aiming for remission. Importantly, with good control of inflammation and adequate use of calcium, vitamin D and bisphosphonates - according to national or international guidelines - steroid-induced osteoporosis is rare over 2 years.
25225283 Determinants of erythrocyte methotrexate polyglutamate levels in rheumatoid arthritis. 2014 Nov OBJECTIVE: Low-dose methotrexate (MTX) is the anchor drug in the treatment for rheumatoid arthritis (RA). Response to MTX is related to the intracellular MTX-polyglutamate (MTX-PG) levels and little is known about its determinants. We aimed to define the determinants of erythrocyte MTX-PG concentrations in 2 prospective cohorts of patients with RA. METHODS: Patients with RA treated with MTX from 2 longitudinal cohorts were included: 93 from the MTX-R study (Rotterdam, the Netherlands derivation cohort), and 247 from the treatment in Rotterdam Early Arthritis Cohort study (validation cohort). MTX-PG concentrations were measured at 3 months of treatment using liquid chromatography/mass spectrometry. The MTX-PG were used as outcome measure. Various sociodemographic, clinical, biochemical, and genetic factors were assessed at baseline. Associations with MTX-PG levels were analyzed using multivariate regression analysis. RESULTS: Age was positively associated with MTX-PG1 (stβ 0.23, p=0.033) and total MTX-PG (stβ 0.23, p=0.018) in the derivation cohort, and with all MTX-PG in the validation cohort (MTX-PG1: stβ 0.13, p=0.04; MTX-PG2: stβ 0.21, p=0.001; MTX-PG3: stβ 0.22, p<0.001; MTX-PG4+5: stβ 0.25, p<0.001; and total MTX-PG: stβ 0.32, p<0.001). Erythrocyte folate levels were positively associated with MTX-PG3 (stβ 0.3, p=0.021) and total MTX-PG levels (stβ 0.32, p=0.022) in the derivation cohort, which was replicated for MTX-PG3 (stβ 0.15, p=0.04) in the validation cohort. Patients with the folylpolyglutamate synthase (FPGS) rs4451422 wild-type genotype had higher concentrations of MTX-PG3 (p<0.05), MTX-PG4+5 (p<0.05), and total MTX-PG (p<0.05) in both cohorts. In the combined cohort, MTX dose was positively associated with levels of MTX-PG3 (stβ 0.23, p<0.001), MTX-PG4+5 (stβ 0.30, p<0.001), and total MTX-PG (stβ 0.20, p=0.002), but negatively associated with MTX-PG2 levels (stβ -0.22, p<0.001). CONCLUSION: Our prospective study shows that higher age, higher MTX dose, higher erythrocyte folate status, and the FPGS rs4451422 wild-type genotype are associated with higher MTX-PG concentrations. While only up to 21% of interpatient variability can be explained by these determinants, this knowledge may aid in the development of personalized treatment in RA.
23274520 The effect of autoimmune arthritis treatment strategies on regulatory T-cell dynamics. 2013 Mar PURPOSE OF REVIEW: Since their discovery over 15 years ago, intensive research has focused on the presence, phenotype and function of FOXP3(+) regulatory T cells (Treg) in autoimmune diseases such as rheumatoid arthritis (RA). The questions of whether Treg deficiencies underlie autoimmune pathology and whether or how Treg-related therapeutic approaches might be successful are still a subject of a vivid debate. In this review we give an overview of how current therapies influence Treg numbers and function in RA and juvenile idiopathic arthritis (JIA) and discuss these findings in the light of new Treg-based intervention strategies for autoimmune arthritis. RECENT FINDINGS: The attempt to relate rheumatic diseases like rheumatoid arthritis and juvenile idiopathic arthritis to Treg has led to somewhat heterogeneous observations. So far, no clear defects in Treg numbers or function have been identified in autoimmune arthritis. The current standard therapies, that is methotrexate and biologicals, are generally effective, but the exact mechanism of action and their effect on Treg is not fully known. Nevertheless, the majority of in-vitro and ex-vivo data point towards a positive influence of these treatments on Treg number and function. These observations are not all consistent, however, and it is not known whether the observed effects on Treg are primary or secondary effects. To safely conduct targeted regulatory T-cell therapy in rheumatic diseases more knowledge about regulatory T-cell function in an inflammatory environment is needed that coincides with the initiative to elucidate the exact mechanism of current therapies.
23194101 A case of urinary incontinence by hydroxychloroquine in a geriatric patient. 2013 Apr WHAT IS KNOWN AND OBJECTIVE: Rheumatoid arthritis is an autoimmune disorder characterized by persistent synovitis and systemic inflammation. Genetic factors account for approximately 50% of cases of rheumatoid arthritis and environmental factors include smoking. Urinary incontinence may occur as a medication adverse effect. We present the first report of a case of hydroxychloroquine-induced urinary incontinence in rheumatoid arthritis. DETAILS OF THE CASE: A 71-year-old female with a history of rheumatoid arthritis developed urinary incontinence as an adverse drug reaction to hydroxychloroquine administered at therapeutic doses. Urinary incontinence remitted with drug withdrawal and reappeared on rechallenge. The Naranjo's algorithm indicated that hydroxychloroquine was a probable cause of this adverse drug reaction. The likely mechanism of this adverse drug is a direct action of the quinolone on the urinary system. WHAT IS NEW AND CONCLUSION: This is the first report of hydroxychloroquine-induced urinary incontinence. The absence of previous reports suggest that the drug rarely causes this adverse effect. Methotrexate is most often used as first-line treatment, and several other drugs are now available to act as Disease-Modifying Antirheumatic Drugs (DMARDs). These drugs may be used alone or combined with methotrexate, most often to increase efficacy and reduce toxicity. The introduction of new biological agents, such as abatacept, rituximab, tocilizumab and inhibitors of tumour necrosis factor, has opened new therapeutic perspectives but are restricted by high costs and risk of infections. Thus, antimalarial drugs, especially the quinolones chloroquine (CQ) and hydroxychloroquine (HCQ), are still in use, and the latter is very efficacious. An advantage of HCQ is its low toxicity compared with other antimalarial drugs. Common side-effects of HCQ and the other antimalarial drugs include gastrointestinal effects such as nausea and vomiting, as well as skin rashes and headache, whereas their most common and severe side-effect is retinopathy. No case of urinopathy has been reported previously with HCQ.
25274900 Patients with rheumatoid arthritis in clinical remission manifest persistent joint inflamm 2014 Nov OBJECTIVE: The purpose of our study was to test the hypothesis that synovitis on magnetic resonance imaging (MRI) and ultrasound (US) observed in patients with rheumatoid arthritis (RA) who meet remission criteria reflects active inflammation on histopathology. METHODS: We analyzed 15 synovial specimens obtained during surgical procedures from 14 patients with RA in clinical remission as defined by the American College of Rheumatology criteria. Histological specimens were scored for hyperplasia of synovial lining and synovial stroma, inflammation, lymphoid follicles, and vascularity. The histology scores were classified as minimal, mild, moderate, or severe disease activity. US and MRI performed within a 4-month period of surgery were scored for disease activity. The correlation between histology and imaging scores was examined. RESULTS: Four of 14 patients were receiving anti-tumor necrosis factor (TNF) therapy, 4 were receiving methotrexate (MTX) alone, 4 were taking MTX and hydroxychloroquine (HCQ), and 1 was taking HCQ and sulfasalazine. Four specimens had severe, 6 moderate, 3 mild, and 2 minimal disease activity on histology. Three of 4 specimens with minimal and mild histology were observed in subjects receiving anti-TNF therapy. Synovitis was noted on greyscale in 80% of joints and Doppler signal in 60%. MRI demonstrated synovitis and bone marrow edema in 86% of images. Positive but not significant correlations were noted between histology and synovitis scores on US. CONCLUSION: Despite clinical remission, histology and imaging studies documented a persistently active disease state that may explain the mechanism for radiographic progression.
24037554 Determining best practices in early rheumatoid arthritis by comparing differences in treat 2013 Nov OBJECTIVE: To determine site variation by comparing outcomes across sites in an early rheumatoid arthritis cohort. METHODS: Sites from the Canadian Early Arthritis Cohort database with at least 40 patients were studied. Comparisons were made among sites in change in 28-joint Disease Activity Score (DAS28), proportion of patients in DAS28 remission, and treatment strategies. RESULTS: The study included 1138 baseline patients at 8 sites, with baseline (SD) age 52 years (16.9); 72% women; 23% erosions; 54% ever smokers; 51% rheumatoid factor-positive; 37% anticitrullinated protein antibody-positive; disease duration 187 (203) days; DAS28 4.5 (1.4). Site had an effect on outcomes when adjusting for confounders. At 6 and 12 months, sites B and H, the 2 largest sites, had the best changes in DAS28 (-1.82 and -2.09, respectively, at 6 mos, and -2.27 for both at 12 mos; p < 0.001). Site H had the most patients in DAS28 remission at 6 months [64.5% compared to other sites that had from 34.1% to 51.7% (p < 0.001)], and at the last followup, sites B and H had the most in remission. Subcutaneous methotrexate was used more overall and earlier at sites B and H. Those sites used less steroid therapy, and site B had the second-highest use of triple disease-modifying antirheumatic drugs at any visit. Medications were increased more in 2 of the 3 smallest sites. Biologics were used by 9 months most in the smallest (50.0%) and then largest (19.6%) sites. CONCLUSION: Sites in an early inflammatory arthritis cohort yielded different outcomes. Better outcomes up to 12 months may result from initial treatment with early combination therapy and/or subcutaneous methotrexate.