Radu Vasilescu

A structured literature review of the burden of illness and unmet needs in patients with rheumatoid arthritis: a current perspective

Abstract While rheumatologists often focus on treatment targets, for many patients with rheumatoid arthritis (RA), control over pain and fatigue, as well as sustaining physical function and quality of life (QoL), is of primary importance. This literature review aimed at examining patients’ and physicians’ treatment aspirations, and identifying the unmet needs for patients with RA receiving ongoing treatment. Searches were performed using MEDLINE, Embase, PsycINFO, and Econlit literature databases for articles published from 2004 to 2014 in the English language. Published literature was screened to identify articles reporting the unmet needs in RA. We found that, despite the wide range of available treatments, RA continues to pose a substantial humanistic and economic burden on patients, and there are still unmet needs across key domains such as pain, physical function, mental function, and fatigue. These findings suggest that there is a need for further treatment advances in RA that address these domains of contemporary unmet need.

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 ≥3 months and had 28-joint disease activity scores (DAS28) reported. Adequately controlled (DAS28 ≤3.2) 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.

Patient access to reimbursed biological disease-modifying antirheumatic drugs in the European region

ABSTRACT Background & Objectives: Biological disease-modifying antirheumatic drugs (bDMARDs) for the treatment of rheumatoid arthritis (RA) are not always accessible to all patients in accordance with international guidelines, partly owing to their high direct costs against a background of restricted healthcare budgets. This study compares the size of RA patient populations with access to reimbursed bDMARDs across 37 European countries, Russia, and Turkey, according to their treatment eligibility defined by European League Against Rheumatism (EULAR) recommendations and national reimbursement criteria. Methods: The size of the RA patient population eligible for bDMARD treatment was estimated in a population model using published RA epidemiological data and clinical criteria defined by 2013 EULAR recommendations along with national reimbursement criteria defined in a survey of the 39 countries in November 2015. Results: According to EULAR recommendations, 32% of the total RA population in the European region is eligible for bDMARD treatment. However, only an average 59% of this EULAR-eligible population remains eligible after applying national reimbursement criteria (from 86% in ‘high access’ to 13% in ‘low-access’ countries). Conclusion: Access to reimbursed bDMARDs remains unequal in the European region. As biosimilars of bDMARDs are introduced, changes in reimbursement criteria may increase access to bDMARDs and reduce this inequality.

Factors influencing 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 ≥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.

Tuberculosis and viral hepatitis infection in Eastern Europe, Asia, and Latin America: impact of tumor necrosis factor-α inhibitors in clinical practice

Tumor necrosis factor-α (TNF-α) inhibitors are increasingly becoming the standard of care for treating a number of inflammatory diseases. However, treatment with TNF-α inhibitors carries an inherent risk of compromising the immune system, resulting in an increased susceptibility to infections and malignancies. This increased risk of infection is of particular concern in Asia, Eastern Europe, and Latin America where tuberculosis (TB) and viral hepatitis are endemic. In this brief review, we examine the literature and review the impact of TNF-α inhibitors on the incidence and the reactivation of latent disease with respect to TB, hepatitis C infection, and hepatitis B infection. Our findings show that TNF-α inhibitors are generally safe, if used with caution. Patients should be screened prior to the initiation of TNF-α inhibitor treatment and given prophylactic treatment if needed. In addition, patients should be monitored during treatment with TNF-α inhibitors and after treatment has stopped to ensure that infections, if detected, are treated promptly and effectively. Our analysis is consistent with other reports and guidelines.

FRI0575 The Unmet Need in The Norwegian Disease-Modifying Antirheumatic Drug Registry

Background Until 2012, the Norwegian disease-modifying antirheumatic drug (NOR-DMARD) registry included patients (pts) initiating treatment (trt) with conventional synthetic DMARDs (csDMARDs) and biologic DMARDs (bDMARDs). The revised NOR-DMARD protocol, implemented 2012–2013, includes bDMARDs only. Objectives Describe the outcomes of methotrexate (MTX) therapy and define the unmet need for further trt options for RA pts after MTX failure in the NOR-DMARD registry. Methods These analyses are based on data from two phases (P) of the NOR-DMARD registry: P1 – pts on csDMARDs and bDMARDs (2007–2011); P2 – pts on bDMARDs only (2012–2015). Using different selection criteria from P1 pts, MTX trt outcomes were assessed as follows: % of pts with inadequate response (IR) to MTX (defined as disease activity score 28–4 erythrocyte sedimentation rate [DAS28]>3.2 at 6 months [mo]); reasons for MTX discontinuation (D/C); % of MTX-IR pts remaining on trt despite DAS28>3.2 or DAS28>5.1. ACR20/50/70 and EULAR good/moderate response rates were assessed using P1 and P2 data in pts receiving bDMARDs as monotherapy (mono), +MTX or +other csDMARDs. Results are presented using descriptive statistics from non-imputed observations. Results P1 and P2 included a total of 2698 and 709 RA trt courses, respectively. Of 780 MTX-naïve pts starting MTX mono in P1, 429 (42.9%) had DAS28>3.2 at 6 mo; 381 of the 780 pts had available DAS28 data at Mo 12, and 30.9% pts had DAS28>3.2 at 12 mo. Furthermore, 58.2% of pts who had DAS28>3.2 at 6 mo remained at DAS28>3.2 at 12 mo. 1364 pts were treated with any csDMARDs in P1, 28/1364 pts had DAS28>5.1 for two consecutive visits and remained on trt. In P1 pts previously exposed to MTX starting any trt other than MTX mono (N=1388), 1005 pts had a reason for MTX D/C listed; 489/1005 (48.7%) pts D/C due to side effects. P1 included 1331 bDMARD trt courses: 279 (21.0%) as mono, 938 (70.5%) +MTX and 114 (8.6%) +other csDMARD. In P2 there were 709 trt courses with bDMARDs: 229 (32.3%) as mono, 413 (58.3%) +MTX and 67 (9.3%) +other csDMARD. In P1, bDMARD mono pts had slightly higher baseline disease activity and slightly worse patient-reported outcomes. In P2, baseline demographics and characteristics were generally similar across trt groups (gps). EULAR and ACR responses at Mo 6 were generally comparable across trt gps in P1, although the bDMARD+other csDMARD gp had numerically higher ACR70 and lower EULAR good responses vs other gps. In P2, ACR20 and ACR50 responses were generally similar between bDMARD trt gps at Mo 6. At Mo 6, numerically more pts on bDMARD mono (18.4%) achieved ACR70 vs bDMARD+MTX (10.7%) and bDMARD+other csDMARD (5.9%); similar results were also observed for EULAR good/moderate responses. % of pts with DAS28 remission at Mo 6 were 54.4% for bDMARD mono; 45.7% for bDMARD+MTX; and 50.0% for bDMARD+other csDMARD (Table). Conclusions Data from the NOR-DMARD registry showed that >40% of MTX-treated pts had not achieved DAS28 low disease activity 6 mo. Despite pts advancement to bDMARDs, almost 50% failed to reach DAS28 remission at follow-up. This demonstrates substantial unmet medical need for pts with moderate to severe RA. Trt grp comparisons will be further explored. Acknowledgement Sponsored by Pfizer Inc. Editorial support provided by CMC (funded by Pfizer Inc). Disclosure of Interest I. Olsen: None declared, T. Kvien Consultant for: AbbVie, BMS, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Hospira, Merck-Serono, MSD, Novartis, Orion Pharma, Pfizer Inc, Roche, Sandoz, UCB, Speakers bureau: AbbVie, BMS, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Hospira, Merck-Serono, MSD, Novartis, Orion Pharma, Pfizer Inc, Roche, Sandoz, UCB, E. Lie Consultant for: AbbVie, Bristol-Myers Squibb, Hospira, Pfizer inc, UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Hospira, Pfizer inc, UCB, R. Vasilescu Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, G. Wallenstein Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, S. Strengholt Shareholder of: Pfizer Inc, Employee of: Pfizer Inc