Clinical characteristics and patient-reported outcomes in patients with inadequately controlled rheumatoid arthritis despite ongoing treatment

Background Despite the wide array of treatments available for rheumatoid arthritis (RA), some patients continue to report unmet clinical needs. We investigated the extent of inadequate disease control in patients with RA. Methods Data were drawn from the Adelphi 2014 RA Disease-Specific Program in France, Germany, Italy, Spain and the UK. Rheumatologists provided patient demographics, comorbidities, satisfaction with RA control and other clinical details. Patients reported their level of satisfaction and completed the EuroQoL 5-Dimensions Health Questionnaire and Work Productivity and Activity Impairment Questionnaire. Patients had been on their current therapy 653 months and had 28-joint disease activity scores (DAS28) reported. Adequately controlled (DAS28 643.2) and inadequately controlled (DAS28 >3.2) patient cohorts were compared using univariate tests. Results Of 1147 patients, 74% were women, the mean age was 52 years and the mean time since RA diagnosis was 7 years. Twenty-seven percent of patients had inadequately controlled RA, whereas 73% had adequately controlled RA. Inadequately controlled patients were more affected clinically versus adequately controlled patients; 69% vs 13% had moderate/severe RA, the current level of pain was 4.6 vs 2.3, and 67% vs 41% experienced flares, respectively (all p<0.0001). Inadequately controlled patients had higher rates of depression (16% vs 5%; p<0.0001), worse health state, greater work and activity impairment, and lower satisfaction rates among the patients and their physicians than the adequately controlled cohort. Conclusion RA was insufficiently controlled in over a quarter of patients despite their current therapy and this had a negative impact on the patients

Factors influencing the use of biologic therapy and adoption of treat-to-target recommendations in current european rheumatology practice

Objective: The aim of this study was to identify factors that influence treatment adjustments and adoption of a treat-to-target (T2T) strategy in patients with rheumatoid arthritis (RA) in European practices. Methods: Cross-sectional data were drawn from the Adelphi 2014 RA Disease Specific Programme. Treatment patterns and clinical characteristics were investigated in patients treated with biologic disease-modifying antirheumatic drugs (bDMARDs) vs non-bDMARDs. For the T2T analysis, patients were subdivided into two subsets (RA diagnosis <2 or 652 years) and compared according to the approach used (no target = no T2T approach; pragmatic = target different from remission; and aspirational = target set as remission). Results: Data from 2,536 patients were analyzed (mean age: 52.76 years and mean time since RA diagnosis: 6.05 years). Of the 1,438 patients eligible to receive bDMARDs, 55% did not receive them. Initiation of bDMARDs in a bDMARD-na\uefve patient was prompted by worsening of the disease. In the RA diagnosis <2 years subset, a T2T approach was not adopted in 58% of the patients, whereas 8% and 34% adopted a pragmatic and aspirational approach, respectively. In the RA diagnosis 652 years subset, 45%, 19%, and 36% of the patients adopted a no target, pragmatic, and aspirational approach, respectively. Physician satisfaction with RA control was lower in the RA diagnosis <2 years subset than in the RA diagnosis 652 years subset (65% vs 77% satisfied, respectively; P<0.0001). Conclusion: This analysis shows that the use of bDMARDs remains suboptimal and that a T2T strategy is not universally adopted

Systematic review and network meta-analysis of combination and monotherapy treatments in disease-modifying antirheumatic drug-experienced patients with rheumatoid arthritis: analysis of American College of Rheumatology criteria scores 20, 50, and 70

Michelle E Orme,1 Katherine S MacGilchrist,2 Stephen Mitchell,2 Dean Spurden,3 Alex Bird31Icera Consulting, Swindon, Wiltshire, UK; 2Systematic Review Department, Abacus International, Bicester, Oxfordshire, UK; 3Pfizer UK Limited, Tadworth, Surrey, UKBackground: Biologic disease-modifying antirheumatic drugs (bDMARDs) extend the treatment choices for rheumatoid arthritis patients with suboptimal response or intolerance to conventional DMARDs. The objective of this systematic review and meta-analysis was to compare the relative efficacy of EU-licensed bDMARD combination therapy or monotherapy for patients intolerant of or contraindicated to continued methotrexate.Methods: Comprehensive, structured literature searches were conducted in Medline, Embase, and the Cochrane Library, as well as hand-searching of conference proceedings and reference lists. Phase II or III randomized controlled trials reporting American College of Rheumatology (ACR) criteria scores of 20, 50, and 70 between 12 and 30 weeks' follow-up and enrolling adult patients meeting ACR classification criteria for rheumatoid arthritis previously treated with and with an inadequate response to conventional DMARDs were eligible. To estimate the relative efficacy of treatments whilst preserving the randomized comparisons within each trial, a Bayesian network meta-analysis was conducted in WinBUGS using fixed and random-effects, logit-link models fitted to the binomial ACR 20/50/70 trial data.Results: The systematic review identified 10,625 citations, and after a review of 2450 full-text papers, there were 29 and 14 eligible studies for the combination and monotherapy meta-analyses, respectively. In the combination analysis, all licensed bDMARD combinations had significantly higher odds of ACR 20/50/70 compared to DMARDs alone, except for the rituximab comparison, which did not reach significance for the ACR 70 outcome (based on the 95% credible interval). The etanercept combination was significantly better than the tumor necrosis factor-α inhibitors adalimumab and infliximab in improving ACR 20/50/70 outcomes, with no significant differences between the etanercept combination and certolizumab pegol or tocilizumab. Licensed-dose etanercept, adalimumab, and tocilizumab monotherapy were significantly better than placebo in improving ACR 20/50/70 outcomes. Sensitivity analysis indicated that including studies outside the target population could affect the results.Conclusion: Licensed bDMARDs are efficacious in patients with an inadequate response to conventional therapy, but tumor necrosis factor-α inhibitor combination therapies are not equally effective.Keywords: bDMARD, rheumatoid arthritis, etanercept, systematic review, network meta-analysis, comparative effectivenes

Expression of the alpha3 nicotinic receptor subunit mRNA in aging and Alzheimer's disease

Changes in the number of high-affinity nicotine binding sites have been widely reported in specific regions of the human brain during aging and in degenerative neurological diseases associated with aging, such as Alzheimer's disease. Nicotinic receptors are highly diverse and a description of the molecular subtypes affected in such conditions has not been achieved to date. To investigate the status of the alpha3 subunit-containing subtypes in such conditions, we assessed by in situ hybridisation the alpha3 mRNA density in the hippocampus, entorhinal cortex and thalamus of Alzheimer's patients and age-matched controls. No significant difference in the expression of the alpha3 mRNA, either qualitative or quantitative, was found between Alzheimer's individuals and controls in any of the analysed areas. This result suggests that the nicotine binding changes occurring in these areas in Alzheimer's patients are not correlated to a variation of the alpha3 mRNA in the same regions. Nevertheless, a negative correlation between the alpha3 mRNA density and the age was observed in the entorhinal cortex of both the Alzheimer's and the normal subjects, suggesting a potentially extensive decay of the alpha3-expressing neurons or loss of alpha3-containing receptors in intact neurons of the entorhinal cortex in the late elderly

Clinical neurochemistry: developments in dementia research based on brain bank material

Brain tissue obtained at autopsy continues to provide unique opportunities in current dementia research. Not only is tissue analysis still essential for diagnosis, but investigation of neurochemical pathology, at a level of resolution beyond current in vivo imaging, continues to provide new insights into the involvement of neurotransmitter signalling systems. These are relevant to therapy which, with respect to symptoms such as cognitive impairment, psychosis and depression, is currently targeted to specific transmitter (cholinergic, dopaminergic and serotonergic) systems. This paper focuses on dopaminergic, cholinergic and histaminergic parameters in Alzheimer's disease (AD), Dementia with Lewy bodies (DLB) and Parkinson's disease (PD). In the normal striatum the dopamine transporter and D2 receptor exhibit distinct rostral-caudal distributions and D2 binding is affected by genetic polymorphism at the Taq 1A locus. The transporter is reduced in both DLB and PD but not AD, correlating with severity of extrapyramidal dysfunction, and receptor abnormalities are apparent in DLB patients responding adversely to neuroleptics. Striatal nicotine receptors are lost in all 3 disorders, further reduced as a result of neuroleptic medication, and elevated as a result of tobacco use. In the thalamus there are selective reductions in presynaptic cholinergic activity in DLB in the reticular nucleus which relate to symptoms of hallucinations and fluctuating consciousness prevalent in this disorder. In the hippocampus coupling of muscarinic M1 receptors, relevant to response to cholinergic therapy, is impaired in areas most affected by beta-amyloid plaques and intact in less affected areas. Analysis of histamine H2 receptors indicates that, despite presynaptic histamine abnormalities in AD, receptor numbers are normal. Such clinically and therapeutically relevant observations on human brain neurochemistry provide a basis for improving therapeutic strategies and prospects of diagnostic in vivo chemical imaging.status: publishe

Factors influencing use of biologic therapy and adoption of treat-to-target recommendations in current European rheumatology practice

Peter C Taylor,1 Rieke Alten,2 Juan J Gomez Reino,3 Roberto Caporali,4 Philippe Bertin,5 Emma Sullivan,6 Robert Wood,6 James Piercy,6 Radu Vasilescu,7 Dean Spurden,8 Jose Alvir,9 Miriam Tarallo10 1Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK; 2Department of Internal Medicine II, Rheumatology, Clinical Immunology, and Osteology, Schlosspark Klinik, University Medicine Berlin, Berlin, Germany; 3Experimental and Observational Rheumatology and Rheumatology Unit, Fundacion Ramon Dominguez and Rheumatology, Hospital Clinico Universitario, Santiago de Compostela, Spain; 4Division of Rheumatology, IRCCS Foundation Policlinico S. Matteo, University of Pavia, Pavia, Italy; 5Service de Rhumatologie, CHU Dupuytren, Limoges, France; 6Real-World Evidence and Epidemiology, Adelphi Real World, Bollington, UK; 7Medical Affairs, International Developed Markets, Pfizer, Brussels, Belgium; 8Health Economics and Outcomes Research, Pfizer Ltd, Tadworth, UK; 9Statistical Research and Data Science Center, Global Product Development, Pfizer Inc, New York, NY, USA; 10Patient and Health Impact, Pfizer Italia Srl, Rome, Italy Objective: The aim of this study was to identify factors that influence treatment adjustments and adoption of a treat-to-target (T2T) strategy in patients with rheumatoid arthritis (RA) in European practices.Methods: Cross-sectional data were drawn from the Adelphi 2014 RA Disease Specific Programme. Treatment patterns and clinical characteristics were investigated in patients treated with biologic disease-modifying antirheumatic drugs (bDMARDs) vs non-bDMARDs. For the T2T analysis, patients were subdivided into two subsets (RA diagnosis <2 or ≥2 years) and compared according to the approach used (no target = no T2T approach; pragmatic = target different from remission; and aspirational = target set as remission).Results: Data from 2,536 patients were analyzed (mean age: 52.76 years and mean time since RA diagnosis: 6.05 years). Of the 1,438 patients eligible to receive bDMARDs, 55% did not receive them. Initiation of bDMARDs in a bDMARD-naïve patient was prompted by worsening of the disease. In the RA diagnosis <2 years subset, a T2T approach was not adopted in 58% of the patients, whereas 8% and 34% adopted a pragmatic and aspirational approach, respectively. In the RA diagnosis ≥2 years subset, 45%, 19%, and 36% of the patients adopted a no target, pragmatic, and aspirational approach, respectively. Physician satisfaction with RA control was lower in the RA diagnosis <2 years subset than in the RA diagnosis ≥2 years subset (65% vs 77% satisfied, respectively; P<0.0001).Conclusion: This analysis shows that the use of bDMARDs remains suboptimal and that a T2T strategy is not universally adopted. Keywords: rheumatoid arthritis, treat-to-target, disease-modifying antirheumatic drug

Factors influencing use of biologic therapy and adoption of treat-to-target recommendations in current European rheumatology practice

Objective: To identify factors that influence treatment adjustments and adoption of a treat-to-target (T2T) strategy in patients with rheumatoid arthritis (RA) in European practices. Methods: Cross-sectional data were drawn from the Adelphi 2014 RA Disease Specific Programme. Treatment patterns and clinical characteristics were investigated in patients treated with biologic disease-modifying antirheumatic drugs (bDMARDs) versus non-bDMARDs. For the T2T analysis, patients were subdivided into two subsets (RA diagnosis &lt;2 or ≥2 years) and compared by the approach used (no target = no T2T approach; pragmatic = target different from remission; aspirational = target set as remission). Results: Data for 2536 patients were analyzed (mean age 52.76 years, mean time since RA diagnosis 6.05 years). Of the 1438 patients eligible to receive bDMARDs, 55% did not receive them. Initiation of bDMARDs in a bDMARD-naïve patient was prompted by worsening of the disease. In the RA diagnosis &lt;2 years subset, a T2T approach was not adopted in 58% of patients, while 8% and 34% adopted a pragmatic and aspirational approach, respectively. In the RA diagnosis ≥2 years subset, 45%, 19%, and 36% of patients adopted a no target, pragmatic, and aspirational approach, respectively. Physician satisfaction with RA control was lower in the RA diagnosis &lt;2 years subset than in the RA diagnosis ≥2 years subset (65% vs 77% satisfied, respectively; P&lt;0.0001). Conclusions: This analysis shows that bDMARD use is still suboptimal and that a T2T strategy is not universally adopted. </p