Pain and Fatigue in Patients With Ankylosing Spondylitis Treated With Tumor Necrosis Factor Inhibitors: Multinational Real-World Findings.

BACKGROUND/OBJECTIVE: Patients with ankylosing spondylitis (AS) experience symptoms and comorbidities that impact their health-related quality of life (HRQoL) and ability to work. This real-world, global survey was conducted among AS patients receiving tumor necrosis factor inhibitors (TNFis) to evaluate both the frequency and severity of persistent symptoms, and the impact of pain and fatigue on HRQoL, employment status, and work activity. METHODS: Patients with AS and their treating physicians from 13 countries across 5 continents completed questionnaires capturing demographics, patient symptoms, current disease status, HRQoL, current therapy, employment status, and Work Productivity and Activity Impairment. RESULTS: Seven hundred five patients who had been receiving a TNFi for 3 months or more and completed both Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) pain and fatigue domains were included in the analysis; of these, 37.6% reported high BASDAI pain scores and 41.3% high BASDAI fatigue scores. Medical Outcomes Study-Short Form, 36-item version 2 domain, 5-dimensional EuroQoL Questionnaire, and 5-dimensional EuroQoL visual analog scale scores were significantly lower (p < 0.0001), and Work Productivity and Activity Impairment scores significantly higher (p < 0.0001), in patients with high levels of pain or fatigue than low levels. CONCLUSIONS: Globally, levels of pain and fatigue remained high in AS patients receiving TNFi treatment, which were significantly associated with reduced HRQoL and work productivity. Such persistent symptoms in usual care suggest a substantial unmet need in AS pharmacologic and nonpharmacologic therapeutic pathways.

Relationship of pain and fatigue with health-related quality of life and work in patients with psoriatic arthritis on TNFi: results of a multi-national real-world study.

BACKGROUND/OBJECTIVE: The incidence of pain and/or fatigue in people with psoriatic arthritis (PsA) is associated with reduced health-related quality of life (HRQoL) and the ability to work, despite modern advanced therapeutic approaches. This real-world, international study examined these relationships in patients with PsA treated with tumour necrosis factor inhibitors (TNFi). METHODS: Data from 13 countries were analysed. Patients with PsA and their physicians completed questionnaires capturing demographics, current therapy, current disease status, HRQoL and work status via Medical Outcomes Study 36-Item Short-Form version 2 (SF-36v2), 3-level 5-dimension EuroQoL questionnaire, Health Assessment Questionnaire Disability Index, and Work Productivity and Activity Impairment (WPAI) questionnaire. RESULTS: 640 patients with PsA were included who had been receiving TNFi for ≥3 months and had completed SF-36v2 bodily pain and vitality domains. Of these, 33.1%, 29.2% and 37.7% of patients reported no, moderate and severe pain, respectively, and 31.9%, 22.5% and 45.6% of patients reported low, moderate and severe fatigue, respectively. Scores across HRQoL variables and WPAI were significantly different across pain and fatigue cohorts (all p<0.0001), with HRQoL and WPAI measures considerably worse in patients with moderate to severe pain or fatigue than those with low pain or fatigue. CONCLUSIONS: Despite treatment with biologic agents such as TNFi, data from this global study demonstrated that substantial pain and/or fatigue persist in patients with PsA and that these are significantly associated with reduced HRQoL, physical function and work productivity. These findings suggest that there is an unmet need for additional PsA therapies.

Biologic Disease-Modifying Antirheumatic Drug Prescription Patterns Among Rheumatologists in Europe and Japan.

INTRODUCTION: Tumor necrosis factor inhibitors (TNFi) are commonly used as first-line therapy (biologic disease-modifying antirheumatic drug [bDMARD] and targeted synthetic DMARD [tsDMARD]: defined as targeted therapy) for patients with moderate-to-severe rheumatoid arthritis (RA), usually combined with conventional synthetic DMARDs (csDMARDs) but sometimes as monotherapy. If treatment fails, patients cycle to another TNFi (cycling) or switch to a targeted therapy with a different mode of action (MOA; switching). The study aimed to examine prescribing patterns and reasons for current RA treatment practice in Europe (EU5: France, Germany, Italy, Spain, UK) and Japan. METHODS: Data were collected from the Adelphi Disease Specific Programme™ (DSP; Q1-Q2 2017). Rheumatologists seeing ≥ 10 (EU5) and ≥ 5 (Japan) patients with RA a month completed Patient Record Forms. Patients ≥ 18 years old, with RA diagnosis and complete RA-targeted therapy history were included. Patients were grouped based on first-line targeted therapy class, and on whether first-line targeted therapy was monotherapy (targeted therapy alone) or combination therapy (targeted therapy and csDMARD). Those patients receiving TNFi at first-line and with ≥ 1 targeted therapy were classified as TNFi cyclers or MOA switchers. Univariate analysis compared factors across groups. Patient demographics and characteristics compared across groups; physician reasoning for targeted therapy change; and time to discontinuation of targeted therapy. RESULTS: In EU5 and Japan, respectively, 1741 and 147 patients were included; at first-line, 80.8% and 64.6% received TNFi and 76.0% and 77.6% received combination therapy. Overall in EU5, more combination therapy than monotherapy patients reached maximum csDMARD dose before first-line targeted therapy (P < 0.05); disease severity was higher in patients initiating TNFi versus non-TNFi (P < 0.05). In Japan, trends were similar but not significant. The most common reason physicians gave for changing therapy following first-line targeted therapy was 'secondary lack of efficacy' (EU5: 46.2%; Japan: 53.8%). In EU5 and Japan, respectively, of 365 and 22 patients who received second-line targeted therapy, 52.1% and 54.5% were MOA switchers. In EU5, TNFi cyclers had longer time from diagnosis to second-line targeted therapy initiation than MOA switchers (P = 0.04). CONCLUSIONS: TNFis were the most commonly prescribed targeted therapy at first-line. Between 10 and 20% of patients prescribed a TNFi as first-line targeted therapy did so without concomitant csDMARD. Almost half of patients cycled to another TNFi at second-line.

Biologic Disease-Modifying Antirheumatic Drug Prescription Patterns for Rheumatoid Arthritis Among United States Physicians.

INTRODUCTION: Some patients with rheumatoid arthritis (RA) using tumor necrosis factor inhibitors (TNFi) experience inefficacy or lack of tolerability and hence switch to another TNFi (cycling) or to a therapy with another mode of action (switching). This study examined patient characteristics, prescribing patterns and treatment practice for RA in the United States. METHODS: Data were from the Adelphi Disease Specific Programme (Q2-Q3 2016). Rheumatologists completed a survey and patient record forms for adult patients with RA who had received ≥ 1 targeted therapy. Patients were grouped by class of first-used targeted therapy, and monotherapy vs. combination therapy. TNFi patients who received ≥ 1 targeted therapy were classified as cyclers or switchers. Univariate analyses compared patient characteristics and physician factors across the analysis groups. RESULTS: Overall, 631 patients received ≥ 1 targeted therapy; 535 were prescribed a TNFi as first targeted therapy, 53 a nonTNFi biologic disease-modifying antirheumatic drug (bDMARD), and 43 tofacitinib. Of 577 patients with known conventional synthetic (cs) DMARD status, 18.7% were prescribed monotherapy and 81.3% combination therapy. Combination therapy patients received significantly more concomitant medications prior to initiation of first targeted therapy than monotherapy patients (P < 0.05). The top reason for physicians to prescribe first use targeted therapy was strong overall efficacy (79.9%). Of 163 patients who progressed to second targeted therapy, 60.7% were cyclers. A lower proportion of cyclers persisted on their first use targeted therapy versus switchers (P = 0.03). The main reason physicians gave for switching patients at this stage was worsening condition (46.6%). CONCLUSIONS: Most patients were prescribed a TNFi as their first targeted therapy; over half then cycled to another TNFi. This suggests other factors may influence second use targeted treatment choice and highlights the need for greater understanding of outcomes associated with subsequent treatment choices and potential benefits of switching.

The multifaceted impact of anxiety and depression on patients with rheumatoid arthritis.

BACKGROUND: The prevalence of mood disturbances such as anxiety and depression is greater in rheumatoid arthritis (RA) patients than in the general population. Given this association, the primary aim of this study was to assess the incremental impact of anxiety or depression on patients with RA from the United States of America (USA) and Europe, independent of the impact of the underlying RA disease. METHODS: Rheumatologists (n = 408) from the USA and 5 European countries completed patient record forms for a predetermined number of RA patients who consulted consecutively during the study period; these patients completed patient-reported questionnaires. Descriptive statistics and multivariate regression were used to investigate the relationship between anxiety and depression with treatment and economic outcomes in RA patients. RESULTS: Of 1015 physician and patient pairs who completed all relevant questionnaire sections, 390 (38.4%) patients self-reported anxiety or depression, while 180 (17.7%) patients were reported to have anxiety or depression by their physicians. Controlling for age, gender, body mass index and clinical factors (flaring and severity), multiple regression analyses suggested that patients with anxiety or depression more often experienced treatment dissatisfaction (odds ratio [OR] 2.28; P < .001), had greater impairment in work (coefficient [ß] = 11.82; P = .001) and usual activity (ß = 14.73; P < .001), greater disability (ß = .35; P < .001), and more often reported unemployment (OR 1.74; P = .001). Multinomial logistic regression revealed discordance between physician and patient satisfaction with treatment. For patients reporting anxiety or depression, physicians were more often satisfied with achievement of current disease control than patients (relative risk ratio 2.19; P = .002). CONCLUSION: Concomitant anxiety or depression was associated with a significant incremental impact on the health-related quality of life and economic aspects of life of patients with RA. In light of observed differences between physician recognition of patient anxiety and/or depression versus patient reporting of anxiety and/or depression symptoms, further research is warranted to develop optimal screening and management of depression and anxiety in patients with RA.

The prevalence and types of discordance between physician perception and objective data from standardized measures of rheumatoid arthritis disease activity in real-world clinical practice in the US.

BACKGROUND: Heterogeneity in assessments of rheumatoid arthritis (RA) disease remission, based on physician judgment and patient self-reports versus standardized measures, have previously been reported. This study explored the prevalence and types of discordance between physician perception versus objective data of RA disease activity in real-world clinical practice in the US. METHODS: Data were from the Adelphi RA Disease Specific Programme (DSP; January to March 2014), a cross-sectional survey of US rheumatologists and their patients. RA remission based on physician judgment versus Disease Activity Score in 28 joints (3)-erythrocyte sedimentation rate (DAS28(3)-ESR) and Clinical Disease Activity Index (CDAI) scores were compared using descriptive analyses; patient and physician factors associated with discordance were identified using bivariate and multivariate analyses. RESULTS: Of 101 rheumatologists participating (completing patient-record forms for 843 patients), 56.4% based assessment of remission on clinical judgment alone. Of 531 patients eligible for the discordance analysis, 49.7% were in remission based on rheumatologists' evaluation, and 30.7% were eligible based on DAS28(3)-ESR. Compared with DAS28(3)-ESR criteria, 25.8% of patients' disease remission was negatively discordant (overestimated remission) based on clinical perception. These patients were mostly administered biologic disease-modifying antirheumatic drugs and were without a treat-to-target strategy followed by their rheumatologist (P < 0.05). These patients were also more likely to have experienced a higher level of pain as well as increased joint inflammation and damage (e.g. destruction of cartilage, thinning of bone, and/or synovium inflammation) compared with concordant patients (P < 0.005). Conversely, 6.8% of rheumatologists were positively discordant (under estimated remission) versus the DAS28(3)-ESR. Sensitivity analysis indicated different levels of discordance using CDAI, with 35.6% negative discordance and 1.3% positive discordance of rheumatologist-assessed disease remission compared with objective data. CONCLUSION: There is discordance between RA remission as assessed by rheumatologist perception versus standardized measures among those in the US DSP sample. Our study identified the factors associated with the discordance which may inform strategies to enhance assessments of RA disease remission.

Sunitinib Treatment Modification in First-Line Metastatic Renal Cell Carcinoma: Analysis of the STAR-TOR Registry.

BACKGROUND/AIM: Sunitinib is the current standard of care for first-line (1L) treatment of metastatic renal cell carcinoma (mRCC). Previous studies suggest that a modified treatment schedule may benefit patients. Our aim was to evaluate efficacy and safety regarding sunitinib treatment modification in 1L treatment of mRCC. MATERIALS AND METHODS: Data were drawn from STAR-TOR, a German real-world registry to evaluate outcomes of patients with mRCC who received 1L sunitinib. Patients were divided into two groups: subsequent treatment modification (SM) or remaining on standard dose/schedule (SS). Time on treatment (TT), progression-free survival (PFS), and overall survival (OS) were estimated. RESULTS: Overall, 297 patients were analyzed; 33% underwent treatment modification. Significant baseline differences between groups were observed; SM patients were older and had a more favourable Karnofsky performance status. SM patients achieved better outcomes than SS patients for median TT (15.1 versus 3.9 months; p<0.0001), PFS (15.1 versus 6.0; p<0.0001), and OS (38.1 versus 13.7; p<0.0001). Diarrhoea (34%/17%), fatigue (30%/11%), hand-foot syndrome (28%/10%), and stomatitis (20%/6%) were more frequently reported in SM versus SS; incidence was reduced following schedule/dose modification (except diarrhoea). CONCLUSION: In addition to AE mitigation, sunitinib treatment modification may help improve efficacy outcomes in mRCC by prolonging treatment duration.

Extent and consequences of inadequate disease control among adults with a history of moderate to severe atopic dermatitis.

Since control of atopic dermatitis (AD) remains challenging but has not been adequately characterized, the objective of this study was to characterize disease control among patients with a history of moderate to severe AD. Data were from the 2014 Adelphi US AD Disease Specific Programme, a cross-sectional survey of physicians (n = 202) and their patients with history of moderate to severe AD (n = 1064, 54% female, 75% white, mean age 40 years). Inadequately controlled AD as rated by the physician was defined as currently flaring; deteriorating/changeable AD; or physician dissatisfaction with current control. The overall inadequate control rate was 58.7% (n = 625), which increased with current AD severity and was observed in 53.4% and 83.4% of patients receiving immunosuppressants and systemic corticosteroids, respectively. Relative to controls, inadequately controlled patients had poorer disease-specific quality of life, higher level of work impairment, greater itch and sleep interference with daily living (all P < 0.05). Multivariate analysis showed factors significantly associated with inadequate control (all P < 0.05), including Hispanic race, symptoms on the head/neck or lower limbs, itch and sleep interference with daily living. A limitation of the study was reliance on accuracy of reporting, potential selection bias and cross-sectional study design. In summary, there was a high rate and substantial impact of physician-rated inadequately controlled disease among patients with a history of moderate to severe AD, suggesting the need for more effective therapies.

Discordance Between Physician- and Patient-Reported Disease Severity in Adults with Atopic Dermatitis: A US Cross-Sectional Survey.

BACKGROUND: There is limited understanding of severity rating of atopic dermatitis in clinical practice. OBJECTIVES: To evaluate the agreement between physician- and patient-rated severity of atopic dermatitis. METHODS: Data were collected from the 2014 Adelphi US Atopic Dermatitis Disease Specific Programme, a cross-sectional survey of physicians and their patients with a history of moderate-to-severe atopic dermatitis; patients voluntarily completed a questionnaire. Current disease severity (mild/moderate/severe), based on personal judgment, was rated independently by patients and their physicians. The weighted kappa statistic identified level of agreement between physicians and patients. Bivariate analyses characterized agreement; multi-nomial logistic regression identified factors associated with discordance. RESULTS: Overall, 678 patients were included (369 [54.4%] were women, 525 [77.4%] were White, mean age was 39.3 years). Agreement was moderate (weighted kappa = 0.52): compared with physician ratings, patient-rated severity was higher in 76 patients (11.2%), lower in 137 patients (20.2%), and matched in 465 patients (68.6%). There were no differences in the rates of agreement between physician and patient ratings based on physician specialty (p = 0.6781), objective severity measures [Eczema Area and Severity Index score (p = 0.5308), percent body surface area affected (p = 0.9872), and current systemic immunosuppressant use (p = 0.9197)]. Multivariate analysis showed patients with a worse quality of life (Dermatology Life Quality Index) were more likely to rate a higher severity (relative risk ratio 1.04, 95% confidence interval 1.00-1.08; p = 0.0460). Physicians were more likely to rate a higher severity with a greater physician-reported sleep disturbance (relative risk ratio 1.71, 95% confidence interval 1.01-2.89; p = 0.0440). CONCLUSIONS: Almost one-third of patients rated atopic dermatitis severity differently from their physicians, supporting the importance of the patient perspective in the severity assessment of atopic dermatitis and the need for greater communication between patients and physicians.