Concept: Psoriatic arthritis
OBJECTIVE: To investigate whether biologic-free remission can be achieved in patients with early, active axial spondyloarthritis (SpA) who were in partial remission after 28 weeks of infliximab (IFX)+naproxen (NPX) or placebo (PBO)+NPX treatment and whether treatment with NPX was superior to no treatment to maintain disease control. METHOD: Infliximab as First-Line Therapy in Patients with Early Active Axial Spondyloarthritis Trial (INFAST) Part 1 was a double-blind, randomised, controlled trial in biologic-naïve patients with early, active, moderate-to-severe axial SpA treated with either IFX 5 mg/kg+NPX 1000 mg/d or PBO+NPX 1000 mg/d for 28 weeks. Patients achieving Assessment of SpondyloArthritis international Society (ASAS) partial remission at week 28 continued to Part 2 and were randomised (1:1) to NPX or no treatment until week 52. Treatment group differences in ASAS partial remission and other efficacy variables were assessed through week 52 with Fisher exact tests. RESULTS: At week 52, similar percentages of patients in the NPX group (47.5%, 19/40) and the no-treatment group (40.0%, 16/40) maintained partial remission, p=0.65. Median duration of partial remission was 23 weeks in the NPX group and 12.6 weeks in the no-treatment group (p=0.38). Mean Bath Ankylosing Spondylitis Disease Activity Index scores were low at week 28, the start of follow-up treatment (NPX, 0.7; no treatment, 0.6), and remained low at week 52 (NPX, 1.2; no treatment, 1.7). CONCLUSIONS: In axial SpA patients who reached partial remission after treatment with either IFX+NPX or NPX alone, disease activity remained low, and about half of patients remained in remission during 6 months in which NPX was continued or all treatments were stopped.
Objective. RA and axial SpA have an important impact on patients' lives. The objective of this study was to explore the reporting of different aspects of that impact in publications, with a focus on differences between diseases and over time.Methods. A systematic literature review retrieved all articles reporting on the life impact of RA or axial radiographic SpA in adults published within the last 10 years and issued from European research. The data were classified into physical impact (including pain, functional assessment and fatigue), psychological impact (including psychological distress and coping) and social impact (including relationships, family and social life). The number of articles published over time was analysed by linear regression.Results. In all, 1352 abstracts were screened and 149 publications (40 056 patients) were analysed: 129 articles (86.5%) concerned RA and 16 (10.7%) concerned axial SpA. The mean number of articles reporting on the physical aspects of impact was 11.4 (s.d. 4.8) per 2-year period, but increased more than 2-fold (from 7 articles in 2001-3 to 15 in 2010-11), in particular due to recent publications on fatigue, whereas the number of articles on psychological aspects [mean 12.4 (s.d. 4.0)] decreased markedly after 2006. Publications reporting on social aspects [mean 8.2 (s.d. 4.1)] remained globally stable.Conclusion. In the era of biologics, there is an interest in the patient-perceived life impact of RA and axial SpA in the European literature, but the impact of RA has been the subject of greater exploration. There are clearly trends over time in the reporting of impact.
In this article, the 2010 European League against Rheumatism (EULAR) recommendations for the management of rheumatoid arthritis (RA) with synthetic and biological disease-modifying antirheumatic drugs (sDMARDs and bDMARDs, respectively) have been updated. The 2013 update has been developed by an international task force, which based its decisions mostly on evidence from three systematic literature reviews (one each on sDMARDs, including glucocorticoids, bDMARDs and safety aspects of DMARD therapy); treatment strategies were also covered by the searches. The evidence presented was discussed and summarised by the experts in the course of a consensus finding and voting process. Levels of evidence and grades of recommendations were derived and levels of agreement (strengths of recommendations) were determined. Fourteen recommendations were developed (instead of 15 in 2010). Some of the 2010 recommendations were deleted, and others were amended or split. The recommendations cover general aspects, such as attainment of remission or low disease activity using a treat-to-target approach, and the need for shared decision-making between rheumatologists and patients. The more specific items relate to starting DMARD therapy using a conventional sDMARD (csDMARD) strategy in combination with glucocorticoids, followed by the addition of a bDMARD or another csDMARD strategy (after stratification by presence or absence of adverse risk factors) if the treatment target is not reached within 6 months (or improvement not seen at 3 months). Tumour necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, biosimilars), abatacept, tocilizumab and, under certain circumstances, rituximab are essentially considered to have similar efficacy and safety. If the first bDMARD strategy fails, any other bDMARD may be used. The recommendations also address tofacitinib as a targeted sDMARD (tsDMARD), which is recommended, where licensed, after use of at least one bDMARD. Biosimilars are also addressed. These recommendations are intended to inform rheumatologists, patients, national rheumatology societies and other stakeholders about EULAR’s most recent consensus on the management of RA with sDMARDs, glucocorticoids and bDMARDs. They are based on evidence and expert opinion and intended to improve outcome in patients with RA.
Effect of denosumab on Japanese patients with rheumatoid arthritis: a dose-response study of AMG 162 (Denosumab) in patients with RheumatoId arthritis on methotrexate to Validate inhibitory effect on bone Erosion (DRIVE)-a 12-month, multicentre, randomised, double-blind, placebo-controlled, phase II clinical trial
To evaluate efficacy and safety of three different regimens of denosumab, a fully human monoclonal antibody to receptor activator of nuclear factor kappa B (RANK) ligand (RANKL), for Japanese patients with rheumatoid arthritis (RA).
Anti-drug antibodies (ADAs) against biologic agents may be clinically significant and potentially alter a biologic drug’s treatment efficacy. This systematic review aims to 1) determine the prevalence of ADAs against infliximab, etanercept, adalimumab, and ustekinumab in psoriasis patients; 2) ascertain whether ADAs are associated with changes in drug efficacy; and 3) explore the use of concomitant methotrexate to prevent ADA formation. Through a systematic search using MEDLINE and EMBASE from January 29, 1950 to March 29, 2013, we identified 25 studies that met the inclusion criteria. Of 7,969 psoriasis patients, 950 patients tested positive for ADAs. Antibodies against infliximab, etanercept, adalimumab, and ustekinumab were reported in 5.4%-43.6%, 0.0%-18.3%, 6.6%-44.8%, and 3.8%-5.5% of patients, respectively. Anti-infliximab antibodies were associated with lower serum infliximab concentrations in three studies and decreased treatment response in five studies. ADAs against etanercept were non-neutralizing and not associated with any apparent effects on clinical response. Anti-adalimumab antibodies were associated with lower serum adalimumab concentrations in three of five studies and reduced clinical efficacy in four studies. Two of six studies reported that anti-ustekinumab antibodies were associated with lower PASI responses, and three ustekinumab studies noted that most of these antibodies were neutralizing. Although the use of concomitant methotrexate with biologic agents to prevent ADA formation in other immune-mediated diseases is promising, their use in psoriasis is sparse. ADA development remains a challenge with biologic therapies and therefore should be considered in psoriasis patients who experience diminished treatment response. This article is protected by copyright. All rights reserved.
Investigate whether the efficacy and safety of intravenous tocilizumab (TCZ) demonstrated at week 52 in patients with early rheumatoid arthritis (RA) are maintained to week 104.
Rheumatoid Arthritis is a chronic disease leading to decreased quality of life with a rather variable response rate to Disease Modifying Anti Rheumatic Drugs. Methotrexate (MTX) is the gold standard therapy in Rheumatoid Arthritis. The Multidrug resistance Related Protein and Multi Drug Resistance protein 1, also called P-glycoprotein-170 transporters can alter the intracellular concentration of different drugs. Methotrexate is an MRP1 substrate and thus the functional activity of MRP1 might have a clinical impact on the efficiency of the Methotrexate-therapy in Rheumatoid Arthritis.
To evaluate the effectiveness and safety of tocilizumab (TCZ) in patients with rheumatoid arthritis (RA) in clinical practice, establishing the optimized regimen and switching from intravenous (IV) to subcutaneous (SC) therapy.
To compare the efficacy, safety, immunogenicity and pharmacokinetics (PK) of SB2 to the infliximab reference product (INF) in patients with moderate to severe rheumatoid arthritis (RA) despite methotrexate therapy.
Background Few blinded trials have compared conventional therapy consisting of a combination of disease-modifying antirheumatic drugs with biologic agents in patients with rheumatoid arthritis who have active disease despite treatment with methotrexate - a common scenario in the management of rheumatoid arthritis. Methods We conducted a 48-week, double-blind, noninferiority trial in which we randomly assigned 353 participants with rheumatoid arthritis who had active disease despite methotrexate therapy to a triple regimen of disease-modifying antirheumatic drugs (methotrexate, sulfasalazine, and hydroxychloroquine) or etanercept plus methotrexate. Patients who did not have an improvement at 24 weeks according to a prespecified threshold were switched in a blinded fashion to the other therapy. The primary outcome was improvement in the Disease Activity Score for 28-joint counts (DAS28, with scores ranging from 2 to 10 and higher scores indicating more disease activity) at week 48. Results Both groups had significant improvement over the course of the first 24 weeks (P=0.001 for the comparison with baseline). A total of 27% of participants in each group required a switch in treatment at 24 weeks. Participants in both groups who switched therapies had improvement after switching (P<0.001), and the response after switching did not differ significantly between the two groups (P=0.08). The change between baseline and 48 weeks in the DAS28 was similar in the two groups (-2.1 with triple therapy and -2.3 with etanercept and methotrexate, P=0.26); triple therapy was noninferior to etanercept and methotrexate, since the 95% upper confidence limit of 0.41 for the difference in change in DAS28 was below the margin for noninferiority of 0.6 (P=0.002). There were no significant between-group differences in secondary outcomes, including radiographic progression, pain, and health-related quality of life, or in major adverse events associated with the medications. Conclusions With respect to clinical benefit, triple therapy, with sulfasalazine and hydroxychloroquine added to methotrexate, was noninferior to etanercept plus methotrexate in patients with rheumatoid arthritis who had active disease despite methotrexate therapy. (Funded by the Cooperative Studies Program, Department of Veterans Affairs Office of Research and Development, and others; CSP 551 RACAT ClinicalTrials.gov number, NCT00405275 .).