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ID PMID Title PublicationDate abstract
27312203 Optimal responses in disease activity scores to treatment in rheumatoid arthritis: Is a DA 2016 Jun 16 BACKGROUND: The overall benefit of intensive treatment strategies in rheumatoid arthritis (RA) remains uncertain. We explored how reductions in disability and improvements in quality of life scores are affected by alternative assessments of reductions in disease activity scores for 28 joints (DAS28) in two trials of intensive treatment strategies in active RA. METHODS: One trial (CARDERA) studied 467 patients with early active RA receiving 24 months of methotrexate monotherapy or steroid and disease-modifying anti-rheumatic drug (DMARD) combinations. The other trial (TACIT) studied 205 patients with established active RA; they received 12 months of treatment with DMARD combinations or biologic agents. We compared changes in the health assessment questionnaire (HAQ) and Euroqol-5D (EQ5D) at trial endpoints in European League Against Rheumatism (EULAR) good and moderate EULAR responders in patients in whom complete endpoint data were available. RESULTS: In the CARDERA trial 98 patients (26 %) were good EULAR responders and 160 (32 %) were EULAR moderate responders; comparable data in TACIT were 66 (35 %) and 86 (46 %) patients. The magnitude of change in the HAQ and EQ5D was greater in both trials in EULAR good responders than in EULAR moderate responders. HAQ scores had a difference in of -0.49 (95 % CI -0.66, -0.32) in the CARDERA and -0.31 (95 % CI -0.47, -0.13) in the TACIT trial. With the EQ5D comparable differences were 0.12 (95 % CI 0.04, 0.19) and 0.15 (95 % CI 0.05, 0.25). Both exceeded minimum clinically important differences in HAQ and EQ5D scores. CONCLUSIONS: We conclude that achieving a good EULAR response with DMARDs and biologic agents in active RA results in substantially improved mean HAQ and EQ5D scores. Patients who achieve such responses should continue on treatment. However, continuing such treatment strategies is more challenging when only a moderate EULAR response is achieved. In these patients evidence of additional clinically important benefits in measures such as the HAQ should also be sought.
25561360 Evaluating relationships between symptom duration and persistence of rheumatoid arthritis: 2015 May BACKGROUND: A prolonged symptom or disease duration at treatment initiation is associated with unfavourable outcomes in rheumatoid arthritis (RA). It is unknown whether this relation is linear, referring to a common 'the-earlier-the-better principle', or whether a transient time frame in which the disease is more susceptible to treatment exists, referring to a 'window of opportunity'. To elucidate this, we evaluated the shape of the associations of symptom duration with persistence of RA. METHODS: Patients with 1987 RA treated with disease modifying antirheumatic drugs (DMARDs) in the Leiden Early Arthritis Clinic (EAC, n=738) and Evaluation et Suivi de POlyarthrites Indifférenciées Récentes (ESPOIR) (n=533) were studied. Cox proportional hazards regression models using natural cubic splines were performed; the log-HR on DMARD-free sustained remission (the opposite of RA persistence) during 5-year follow-up was plotted against symptom duration. Discrimination was measured using time-dependent receiver operator characteristic curves. Subanalyses were performed stratified for the DMARDs used (methotrexate or other conventional DMARDs) and for anticitrullinated peptide antibody (ACPA). RESULTS: 11.5% (85/738) and 5.4% (29/533) of EAC and ESPOIR RA patients achieved DMARD-free sustained remission. In both cohorts and all analyses, the curves depicting the log-HRs on remission in relation to symptom duration were not linear. The symptom duration with optimal discriminative ability was 14.9 weeks (95% CI 12.3 to 16.0; area under the curve (AUC) 0.61) in the EAC and 19.1 weeks (95% CI 12.3 to 28.0; AUC 0.59) in ESPOIR. For ACPA-positive RA, this was 11.4 weeks (95% CI 7.7 to 79.0; AUC 0.56) and for ACPA-negative RA 15.0 weeks (95% CI 9.7 to 48.7; AUC 0.56). CONCLUSIONS: The association between symptom duration and RA persistence is not linear, suggesting the presence of a confined period in which RA is more susceptible to treatment.
26712373 Ultrasound-detected activity in rheumatoid arthritis on methotrexate therapy: Which joints 2016 Mar The aim of the study was to investigate the predictive value of different reduced joint ultrasound (US) assessments of synovitis and tenosynovitis in relation to unstable remission in a cohort of rheumatoid arthritis (RA) patients on methotrexate therapy. Forty-seven RA patients (38 women, 9 men), being treated with methotrexate (MTX), in clinical remission as judged by their consultant rheumatologist were evaluated for disease activity according to the Disease Activity Score (DAS) 28 at baseline and 6 months. Sustained remission and unstable remission were defined according to the baseline and 6-month DAS28 and changes in RA therapy during the follow-up. Each patient underwent at baseline a B-mode and power Doppler (PD) assessment of 44 joints and 20 tendons/tendon compartments by a rheumatologist blinded to the clinical and laboratory data. B-mode synovial hypertrophy (SH), synovial PD signal, B-mode tenosynovitis, and Doppler tenosynovitis were scored 0-3. The presence and index of synovial PD signal in 44 joints [odds ratio (OR) 8.21 (p = 0.016) and OR 2.20 (p = 0.049), respectively] and in 12 joints [OR 5.82 (p = 0.041) and OR 4.19 (p = 0.020), respectively], the presence of SH in wrist and MCP joints [OR 4.79 (p = 0.045)], and the presence of synovial PD signal in wrist-MCP-ankle-MTP joints [OR 4.62 (p = 0.046)] were predictors of unstable remission. The 12-joint or wrist-hand-ankle-MTP US assessments can predict unstable remission in RA patients in apparent clinical remission being treated with MTX.
25660991 Relapse rates in patients with rheumatoid arthritis in stable remission tapering or stoppi 2016 Jan OBJECTIVE: To prospectively analyse the risk for disease relapses in patients with rheumatoid arthritis (RA) in sustained remission, either continuing, tapering or stopping disease-modifying antirheumatic drugs (DMARDs) in a prospective randomised controlled trial. METHODS: Reduction of Therapy in patients with Rheumatoid arthritis in Ongoing remission is a multicentre, randomised controlled, parallel-group phase 3 trial evaluating the effects of tapering and stopping all conventional and/or biological DMARDs in patients with RA in stable remission. Patients (disease activity score 28 (DAS28)<2.6 for least 6 months) were randomised into three arms, either continuing DMARDs (arm 1), tapering DMARDs by 50% (arm 2) or stopping DMARDs after 6 months tapering (arm 3). The primary endpoint was sustained remission during 12 months. RESULTS: In this interim analysis, the first 101 patients who completed the study were analysed. At baseline, all patients fulfilled DAS28 remission and 70% also American College of Rheumatology- European League Against Rheumatism Boolean remission. 82.2% of the patients received methotrexate, 40.6% biological DMARDs and 9.9% other DMARDs. Overall, 67 patients (66.3%) remained in remission for 12 months, whereas 34 patients (33.7%) relapsed. The incidence of relapses was related to study arms (p=0.007; arm 1: 15.8%; arm 2: 38.9%; arm 3: 51.9%). Multivariate logistic regression identified anticitrullinated protein antibodies (ACPA) positivity (p=0.038) and treatment reduction (in comparison to continuation) as predictors for relapse (arm 2: p=0.012; arm 3: p=0.003). CONCLUSIONS: This randomised controlled study testing three different treatment strategies in patients with RA in sustained remission demonstrated that more than half of the patients maintain in remission after tapering or stopping conventional and biological DMARD treatment. Relapses occurred particularly in the first 6 months after treatment reduction and were associated with the presence of ACPA. TRIAL REGISTRATION NUMBER: 2009-015740-42.
26558294 A case of rheumatoid arthritis with methotrexate related lymphoproliferative diseases of t 2018 May Methotrexate (MTX) is the first choice disease-modifying antirheumatic drug (DMARD) for rheumatoid arthritis (RA) and is referred to as an "anchor drug"; its use has been steadily increasing annually. However, MTX-related lymphoproliferative diseases (MTX-LPDs) have emerged as important complications in the patients with RA. There have been no reports of intra-articular MTX-LPDs of the patients with RA. Atypical cells were found in the patient's joint fluid by cytological examinations, and MTX-LPDs were suspected. The patient discontinued MTX and open synovectomy was performed. The histological findings and immunohistochemical staining of the specimens confirmed the diagnosis of diffuse large B-cell lymphoma (DLBCL) of MTX-LPDs. After the operation of the patient's left knee joint, pains and swollen joint disappeared with no relapse. The cytological examinations of the synovial fluid followed by knee operation were effective for early diagnosis of MTX-LPD. MTX discontinuation with no chemotherapy followed up with a knee operation improved the recovery of the MTX-LPD.
25889222 Patients lacking classical poor prognostic markers might also benefit from a step-down glu 2015 Apr 9 INTRODUCTION: Considering a lack of efficacy data in patients with early rheumatoid arthritis (eRA) presenting without classical markers of poor prognosis, we compared methotrexate (MTX) with or without step-down glucocorticoids in the CareRA trial. METHODS: Disease-modifying antirheumatic drug-naïve patients with eRA were stratified into a low-risk group based on prognostic markers that included non-erosiveness, anti-citrullinated protein antibodies and rheumatoid factor negativity and low disease activity (Disease Activity Score in 28 joints based on C-reactive protein (DAS28(CRP)) ≤3.2). Patients were randomized to 15 mg of MTX weekly (MTX with tight step-up (MTX-TSU)) or 15 mg of MTX weekly with prednisone bridging, starting at 30 mg and tapered to 5 mg daily from week 6 (COmbinatie therapie bij Reumatoïde Artritis (COBRA Slim)). A TSU approach was applied. Outcomes assessed were DAS28(CRP)-determined remission, cumulative disease activity, Health Assessment Questionnaire (HAQ) scores and adverse events (AEs) after 16 treatment weeks. RESULTS: We analyzed 43 COBRA Slim and 47 MTX-TSU patients and found that 65.1% in the COBRA Slim group and 46.8% in the MTX-TSU group reached remission (P = 0.081). Mean ± standard deviation area under the curve values of DAS28(CRP) were 13.84 ± 4.58 and 11.18 ± 4.25 for the MTX-TSU and COBRA Slim patients, respectively (P = 0.006). More COBRA Slim patients had an HAQ score of 0 (51.2% versus 23.4%, P = 0.006) at week 16. Therapy-related AEs between groups did not differ. CONCLUSION: In patients with low-risk eRA, MTX with step-down glucocorticoid bridging seems more efficacious than MTX step-up monotherapy, with a comparable number of AEs observed over the first 16 treatment weeks. TRIAL REGISTRATION: EU Clinical Trials Register Identifier: EudraCT number 2008-007225-39 . Registered 5 November 2008.
26428206 Concomitant Methotrexate Protects Against Total Knee Arthroplasty in Patients with Rheumat 2015 Dec OBJECTIVE: To determine the effects of concomitant methotrexate (MTX) on the incidence of total knee arthroplasty (TKA) resulting from the progression of joint destruction in patients with rheumatoid arthritis (RA) during longterm treatment with tumor necrosis factor (TNF) inhibitors. METHODS: A total of 155 patients with RA (310 knee joints) received TNF inhibitors at our institute between May 1, 2001, and May 31, 2008. A total of 111 symptomatic (tender and/or swollen) knee joints in 68 patients were retrospectively studied over the course of a minimum of 5 years of followup. The median (interquartile range) followup period was 8.1 (7.0-9.3) years. All data were analyzed using the knee joint as the statistical unit of analysis. TKA during treatment with TNF inhibitors was used as the outcome variable in predictive analyses. The cumulative incidence of TKA was compared by concomitant or no MTX use (MTX±). RESULTS: There were 79 subjects (71%) who received concomitant MTX. According to Kaplan-Meier estimates, the cumulative incidence of TKA for the MTX+ group was significantly lower than that for the MTX- group (24% vs 45% at 5 yrs, respectively, p = 0.035). Multivariate analysis using the Cox proportional hazards model revealed that concomitant MTX (HR 0.44, 95% CI 0.22-0.89), Larsen grade (HR 2.93, 95% CI 1.94-4.41), and older age at baseline (HR 1.04, 95% CI 1.01-1.08) were independent predictors of TKA. CONCLUSION: Concomitant MTX reduces the incidence of TKA by 56% in patients with RA during longterm treatment with TNF inhibitors.
25547018 Cost-effectiveness of tocilizumab, a humanized anti-interleukin-6 receptor monoclonal anti 2015 Jul OBJECTIVES: To evaluate the cost-effectiveness of tocilizumab in patients with rheumatoid arthritis (RA) in a real-world setting in Japan. METHODS: The cost-effectiveness was determined using a Markov model-based probabilistic simulation. Data from RA patients registered in the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) cohort study between April 2007 and April 2011 were extracted using a pair-matching method: tocilizumab group (n = 104), patients who used at least 1 disease-modifying anti- rheumatic drug and in whom tocilizumab treatment was initiated; methotrexate group (n = 104), patients in whom methotrexate treatment was initiated for the first time or after an interruption of 6 or more months. Assuming a 6-month cycle length, health benefits and costs were measured over a lifetime and discounted at an annual rate of 3%. RESULTS: Compared with methotrexate treatment, lifetime costs and quality-adjusted life years (QALYs) for tocilizumab treatment were approximately 1.5- and 1.3-times higher, respectively. Incremental cost per QALY gained with tocilizumab was $49,359, which was below the assumed cost-effectiveness threshold of $50,000 per QALY. The probability of tocilizumab being cost- effective was 62.2%. CONCLUSION: The simulation model using real-world data from Japan showed that tocilizumab (at a certain price) may improve treatment cost-effectiveness in patients with moderate-to-severe RA by enhancing quality-adjusted life expectancy.
26037777 Evaluation of the Disease Activity Score in Twenty-Eight Joints-Based Flare Definitions in 2015 Dec OBJECTIVE: To assess the flare rate using published criteria (Disease Activity Score in 28 joints [DAS28-2] increase between visits of >1.2 or >0.6 if current DAS28 ≥3.2) in patients receiving constant treatment, and to compare published flare criteria to criteria used by study investigators after biologic treatment discontinuation in the ACT-RAY study. METHODS: Patients with rheumatoid arthritis (n = 553) were randomized to add tocilizumab to ongoing methotrexate, or switch to tocilizumab plus placebo. If DAS28 ≤3.2 occurred at week 24, treatment remained constant until week 52; here we assessed the DAS28-2 flare rate. Between weeks 52 and 104, patients in sustained remission (DAS28 <2.6 at 2 consecutive visits 12 weeks apart) discontinued tocilizumab and were assessed every 4 weeks. Per protocol, flare was defined as a worsening of disease activity that required treatment beyond the permitted therapy based on investigator opinions (investigator flare) and was compared with the DAS28-2 definition. RESULTS: After tocilizumab discontinuation, DAS28-2 was sensitive (88-100%), but not specific (57-65%), for detecting investigator flare. Under constant treatment, DAS28-2 criteria were met in 136 cases per 100 patient-years despite stable disease activity. Sustained flares were infrequent. Other DAS28-based criteria led to similar conclusions. CONCLUSION: DAS28-based flare occurred more often than investigator-defined flares after biologic agent discontinuation. More stringent criteria may be more appropriate for clinical practice.
26315585 Which patients with rheumatoid arthritis, spondyloarthritis, or juvenile idiopathic arthri 2015 Sep OBJECTIVES: Limited information is available about the characteristics of patients with active inflammatory rheumatic diseases who start TNF-α antagonist therapy. Our objective was to assess TNF-α antagonist prescription patterns in this context in France. METHODS: Between 2007 and 2009, 102 rheumatologists, internists, and pediatricians in French university hospitals and private practice prospectively recruited biologics-naïve patients with active rheumatoid arthritis (RA) (DAS28>3.2 despite methotrexate therapy), spondyloarthritis (SA) (BASDAI≥4 despite non-steroidal anti-inflammatory drug [NSAID] use), and juvenile idiopathic arthritis (JIA) (unresponsive to methotrexate). Patients were monitored prospectively for 1 year. RESULTS: Of the 543 RA, 287 SA, and 53 JIA patients included in the study, 382 RA, 171 SA, and 28 JIA patients had complete follow-up data available after 1 year. Among these patients, 110/382 (28.8%) with RA, 81/171 (47.4%) with SA, and 26/28 (92.9%) with JIA received at least one TNF-α antagonist dose during the 1-year follow-up. The main physician-reported reason for not starting TNF-α antagonists in patients with RA or SA was low disease activity (72% for RA and 67% for SA); absence of TNF-α antagonist therapy was due to patient refusal in only 10% and to contraindications in 6% to 7% of cases. CONCLUSIONS: In France, TNF-α antagonists, which are fully reimbursed by the national health insurance system, were used almost routinely in JIA patients unresponsive to methotrexate and were given to about half the SA patients with BASDAI≥4 despite NSAID use and a third of RA patients with DAS28>3.2 despite methotrexate therapy.
26638162 A systematic review of interventions to improve knowledge and self-management skills conce 2016 Jan This systematic review aimed to determine the effectiveness of interventions for improving knowledge and/or self-management skills concerning contraception, pregnancy and breastfeeding in people with rheumatoid arthritis (RA). We searched four databases (MEDLINE, CINAHL, Cochrane Trials, PsycINFO) using a comprehensive search strategy. Studies were eligible if they were prospective, published in English from 2004 to 2015, included participants with RA and tested an intervention designed to improve knowledge and/or self-management skills relating to family planning, pregnancy or breastfeeding. As no studies met the latter criterion, the search strategy was expanded to include all prospective studies evaluating RA educational and/or self-management interventions. Data on study characteristics, participant characteristics and programme content were extracted to summarise the evidence base for interventions to support people with RA during their reproductive years. Expanded literature searches identified 2290 papers, of which 68 were eligible. Of these, nine papers (13%) specifically excluded pregnant women/breastfeeding mothers or recruited only older people. Only one study (1%) explicitly evaluated pregnancy-focused education via a motherhood decision aid, while eight studies (12%) incorporated relevant (albeit minor) components within broader RA educational or self-management interventions. Of these, three studies provided methotrexate education in relation to conception/pregnancy/breastfeeding; three incorporated discussions on RA and relationships, impact of RA on the family or sexual advice; one provided information regarding contraception and fertility; and one issued a warning regarding use of biologic therapy in pregnancy/breastfeeding. In conclusion, information regarding family planning, pregnancy or breastfeeding represents a negligible part of published RA educational interventions, with scope to develop targeted resources.
27253239 Comparative efficacy of biological agents in methotrexate-refractory rheumatoid arthritis 2017 May BACKGROUND/AIMS: Biological agents (biologics) targeting proinflammatory signaling have emerged as an important treatment option in rheumatoid arthritis (RA). Despite the clinical effectiveness of biologics for patients with RA who do not respond to 'traditional' disease-modifying anti-rheumatic drugs (DMARDs), there are concerns regarding their cost and long-term safety. In this study, we aimed to compare the efficacy of various biologics and traditional DMARDs in RA patients refractory to methotrexate (MTX). METHODS: Four DMARDs (hydroxychloroquine, sulfasalazine, MTX, lef lunomide) and five anti-tumor necrosis factor drugs (adalimumab, etanercept, golimumab, inf liximab, and certolizumab) were selected. A systematic search of published studies was performed from inception through July 2013. Randomized trials of adults with MTX-refractory RA comparing two or more of the selected medications were included. Among 7,938 titles identified, in total, 16 head-to-head trials were selected. Two reviewers independently abstracted the study data and assessed methodological quality using the Cochrane Risk of Bias. Comparative efficacy was analyzed using a Bayesian mixed treatment comparison (MTC). RESULTS: In total, 9, 4, and 11 studies were included for the outcome measures of the Health Assessment Questionnaire (HAQ), Disease Activity Score 28-erythrocyte sedimentation rate (DAS28-ESR) < 2.6 (remission), and American College of Rheumatology (ACR) 70 response, respectively. The treatments with the highest efficacy for each outcome measure were certolizumab combined with MTX, golimumab combined with MTX, and certolizumab combined with MTX, respectively. CONCLUSIONS: Based on MTC analysis, using data from published randomized controlled trials, certolizumab and golimumab combined with MTX showed the highest efficacy in the three outcome measures (HAQ, DAS28-ESR < 2.6, and ACR 70 response) in MTX-refractory RA patients.
27002721 Precursor miR-499a Variant but not miR-196a2 is Associated with Rheumatoid Arthritis Susce 2016 Jun INTRODUCTION: Rheumatoid arthritis (RA) has a complex component induced by several genes that interact together with environmental and hormonal factors. We aimed to investigate the association of miR-196a2 rs11614913 (C/T) and miR-499a rs3746444 (A/G) polymorphisms and their combination with RA susceptibility and disease activity in an Egyptian population, and to evaluate their impact on methotrexate drug response and toxicity. MATERIALS AND METHODS: Bioinformatics databases were searched to select potential micro RNA (miRNA)-messenger RNA (mRNA) interactions involved in RA pathogenesis. Ninety-five RA patients diagnosed according to the American College of Rheumatology and 200 healthy controls were genotyped using real-time polymerase chain reaction technology. RESULTS: In overall and stratified analysis, miR-499a, but not miR-196a2, was associated with RA risk. Heterozygote carriers with rs3746444*A/G displayed protection against developing RA (p = 0.005) with an odds ratio of 0.2 (95 % confidence interval 0.17-0.62). The carriage of the combinations (miR499a*AG + miR196a2*CC) and (miR499a*AA + miR196a2*TT) were 3 and 7.5 times more likely to develop RA, respectively, while the combinations (miR499a*GG + miR196a2*CC), (miR499a*AG + miR196a2*TT) and (miR499a*AA + miR196a2*CT) show less susceptibility to have RA disease (all p < 0.05). rs3746444*AA genotype had a higher disease activity score (DAS28) [p = 0.023], tender joint count (TJC) (p = 0.007), and methotrexate-induced gastrointestinal toxicity (p = 0.043) compared with both AG/GG genotypes. rs11614913*C carriers were associated with higher DAS28 activity (p = 0.021). Homozygote male patients (CC and TT) had higher TJC (p = 0.046) and higher rheumatoid factor levels (p = 0.026), whereas, TT homozygote females had higher levels of ALT (p = 0.022). CONCLUSIONS: Different genotypes of miR-499a rs3746444 single nucleotide polymorphisms (SNPs) are associated with RA risk, disease activity, and methotrexate toxicity in our population. In combination with specific miR-196a2 rs11614913 genotypes, this risk could increase or decrease according to the type of combination. Further functional analysis of the SNP and its impact on mRNA targets is required to confirm the relationship between genotype and phenotype.
27307526 Methotrexate Dosage Reduction Upon Adalimumab Initiation: Clinical and Ultrasonographic Ou 2016 Aug OBJECTIVE: To examine the clinical and ultrasonographic (US) outcomes of reducing methotrexate (MTX) dosage upon initiating adalimumab (ADA) in MTX-inadequate responders with moderately to severely active rheumatoid arthritis (RA). METHODS: MUSICA (NCT01185288) was a double-blind, randomized, parallel-arm study of 309 patients with RA receiving MTX ≥ 15 mg/week for ≥ 12 weeks before screening. Patients were randomized to high dosage (20 mg/week) or low dosage (7.5 mg/week) MTX; all patients received 40 mg open-label ADA every other week for 24 weeks. The primary endpoint was Week 24 mean 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP) to test for noninferiority of low-dosage MTX using a 15% margin. US images were scored using a 10-joint semiquantitative system incorporating OMERACT definitions for pathology, assessing synovial hypertrophy, vascularity, and bony erosions. RESULTS: Rapid improvement in clinical indices was observed in both groups after addition of ADA. The difference in mean DAS28-CRP (0.37, 95% CI 0.07-0.66) comparing low-dosage (4.12, 95% CI 3.88-4.34) versus high-dosage MTX (3.75, 95% CI 3.52-3.97) was statistically significant and non-inferiority was not met. Statistically significant differences were not detected for most clinical, functional, and US outcomes. Pharmacokinetic and safety profiles were similar. CONCLUSION: In MUSICA, Week 24 mean DAS28-CRP, the primary endpoint, did not meet non-inferiority for the low-dosage MTX group. Although the differences between the 2 MTX dosage groups were small, our study findings did not support routine MTX reduction in MTX inadequate responders initiating ADA.
25849461 Periodontitis and Porphyromonas gingivalis in preclinical stage of arthritis patients. 2015 PURPOSE: To determine whether the presence of periodontitis (PD) and Porphyromonas gingivalis (Pg) in the subgingival biofilm associates with the development of rheumatoid arthritis (RA) in treatment naïve preclinical stage of arthritis patients. METHODS: We conducted a prospective cohort study of 72 consecutive patients with arthralgia who had never been treated with any anti-rheumatic drugs or glucocorticoids. Periodontal status at baseline was assessed by dentists. PD was defined stringently by the maximal probing depth≧4 mm, or by the classification by the 5th European Workshop in Periodontology (EWP) in 2005 using attachment loss. Up to eight plaque samples were obtained from each patient and the presence of Pg was determined by Taqman PCR. The patients were followed up for 2 years and introduction rate of methotrexate (MTX) treatment on the diagnosis of RA was compared in patients with or without PD or Pg. RESULTS: Patients with PD (probing depth≧4mm) had higher arthritis activity (p = 0.02) and higher risk for future introduction of MTX treatment on the diagnosis of RA during the follow up than patients without PD (Hazard ratio 2.68, p = 0.03). Arthritis activity and risk for MTX introduction increased with the severity of PD assessed by EWP, although not statistically significant. On the other hand, presence of Pg was not associated with arthritis activity (p = 0.72) or the risk for MTX introduction (p = 0.45). CONCLUSION: In treatment naïve arthralgia patients, PD, but not the presence of Pg, associates with arthritis activity and future requirement of MTX treatment on the diagnosis of RA.
26718689 Tick-borne encephalitis (TBE) vaccine to medically immunosuppressed patients with rheumato 2016 Jan 27 BACKGROUND: Tick-borne Encephalitis (TBE) is endemic in south-eastern Sweden as well as in the Baltic regions, Central Europe and Russia. Ageing and immunosuppressed individuals are more prone to severe disease and neurological complications. We assessed the immunogenicity of TBE-vaccine in rheumatoid arthritis (RA) patients treated with tumor necrosis factor-inhibitors (TNFi) and/or methotrexate (MTX). METHODS: TBE vaccine, FSME-Immune(®) or Encepur(®), was administered to non-immune RA patients as well as age and gender matched healthy controls. Individuals <60 years of age were given three doses at month 0, 1, 12. Individuals ≥ 60 years old were given an additional priming dose at month 3, i.e. a total of four doses. Tick-borne encephalitis neutralizing antibodies were assessed by a rapid fluorescent focus inhibition test. RESULTS: The study population consisted of 66 patients and 56 age and gender matched healthy controls. Median age was 58.5 years. The patients were either treated with TNFi (n=16), TNFi+MTX (n=36) or MTX (n=14). After the last TBE-vaccine dose, given one year after the first, 39% of the patients compared to 79% of the healthy controls had seroprotective levels (p=<0.05). CONCLUSIONS: Standard TBE-vaccine schedule does not confer enough immunogenicity in this group of immunosuppressed patients, who should be carefully informed about a higher risk for vaccination failure and risk of infection when exposed in high-endemic areas.
26290587 A patient-initiated DMARD self-monitoring service for people with rheumatoid or psoriatic 2016 Jul OBJECTIVE: To determine the effectiveness of a patient-initiated disease-modifying antirheumatic drugs (DMARD) self-monitoring service for people with rheumatoid (RA) or psoriatic arthritis (PsA) on methotrexate. METHODS: A two-arm, single-centre, randomised controlled trial assessing superiority in relation to healthcare use, clinical and psychosocial outcomes. Participants were 100 adults with either RA or PsA on a stable dose of methotrexate, randomly assigned to usual care or the patient-initiated service. Intervention participants were trained how to understand and interpret their blood tests and use this information to initiate care from their clinical nurse specialist (CNS). The primary outcome was the number of outpatient visits to the CNS during the trial period. Differences between groups were analysed using Poisson regression models. Secondary outcomes were collected at baseline and after the third and sixth blood tests. Disease activity was measured using either the Disease Activity Score in 28 joints or Psoriatic Arthritis Response Criteria (PsARC), pain and fatigue using a visual numeric scale and the Health Assessment Question-II, Hospital Anxiety and Depression Scale and SF12 were completed to assess disability, mood and quality of life, respectively. Differences between groups over time on secondary outcomes were analysed using multilevel models. RESULTS: The patient-initiated DMARD self-monitoring service was associated with 54.55% fewer visits to the CNS (p<0.0001), 6.80% fewer visits to the rheumatologist (p=0.23) and 38.80% fewer visits to the general practitioner (p=0.07), compared with control participants. There was no association between trial arm and any of the clinical or psychosocial outcomes. CONCLUSIONS: The results suggest that a patient-initiated service that incorporates patients' self-monitoring DMARD therapy can lead to significant reductions in healthcare use, while maintaining clinical and psychosocial well-being. TRIAL REGISTRATION NUMBER: ISRCTN21613721.
26994322 Janus kinase inhibitors for rheumatoid arthritis. 2016 Jun Treatment of autoimmune diseases, such as rheumatoid arthritis (RA), has advanced substantially over the past decade with the development of biologics targeting inflammatory cytokines. Recent progress in treating RA has been achieved with janus kinase (JAK) inhibitors (Jakinibs), an orally available disease-modifying anti-rheumatic drug targeting the intracellular kinase JAK and with similar efficacy to biologics. The first Jakinib approved for RA was tofacitinib, which exerted superiority to methotrexate and non-inferiority to tumor necrosis factor (TNF) inhibitors. In recent years, the Jakinib baricitinib has demonstrated superiority to both methotrexate and a TNF inhibitor, adalimumab. Given these promising findings, Jakinibs are expected to represent the next generation compounds for treating RA, and a number of Jakinibs are currently in clinical trials. Jakinibs can differ substantially in their selectivity against JAKs; tofacitinib and baricitinib target multiple JAKs, whereas the most recently developed Jakinibs target only a single JAK. The influence of Jakinib selectivity on efficacy and side effects is of great interest, requiring further careful observation.
25433918 Methotrexate revisited: considerations for subcutaneous administration in RA. 2015 Feb Rheumatoid arthritis (RA) is associated with significant disability, morbidity, early mortality, and substantial financial burden. Despite newer antirheumatics, methotrexate (MTX) remains the most widely used disease-modifying antirheumatic drug. Subcutaneous (SC) MTX provides consistent, reliable delivery, with improved absorption and enhanced polyglutamization leading to increased response rates and fewer gastrointestinal side effects than oral MTX. Optimizing MTX with use of the SC formulation can improve outcomes and may delay or negate the need for costly biologics.
24288014 Discontinuation of adalimumab after achieving remission in patients with established rheum 2015 Feb OBJECTIVES: To investigate the possibility of discontinuing adalimumab (ADA) for 1 year without flaring (DAS28-erythrocyte sedimentation rate (ESR) ≥3.2), and to identify factors enabling established patients with rheumatoid arthritis (RA) to remain ADA-free. METHODS: Of 197 RA patients treated with ADA+methotrexate (MTX), 75 patients who met the ADA-free criteria (steroid-free and sustained DAS28-ESR remission for 6 months with stable MTX doses) were studied for 1 year. RESULTS: The mean disease duration and DAS28-ESR score in 75 patients was 7.5 years and 5.1 at baseline, respectively. The proportion of patients who sustained DAS28-ESR <2.6 (48%) and DAS28-ESR <3.2 (62%) for 1 year were significantly lower in the ADA discontinuation group than in the ADA continuation group; however, in patients with deep remission (DAS28-ESR ≤1.98) identified by receiver operating characteristics analysis following logistic analysis, these rates increased to 68% and 79%, respectively, with no significant difference between both groups. Remarkably, ADA readministration to patients with flare was effective in returning DAS28-ESR to <3.2 within 6 months in 90% and 9 months in 100% patients; among the patients who sustained DAS28-ESR <3.2 during ADA discontinuation, 100% remained in structural remission and 94% in functional remission. CONCLUSIONS: The possibility of remaining ADA-free for 1 year was demonstrated in established patients with RA with outcomes that ADA can be discontinued without flaring in 79% patients with deep remission, with similar rates in the ADA continuation group, and showed no functional or structural damage in patients with DAS28-ESR <3.2. ADA readministration to patients with flare during ADA discontinuation was effective.