Comparison of Different Remission and Low Disease Definitions in Psoriatic Arthritis and Evaluation of Their Prognostic Value.

OBJECTIVE: There is no agreement on the optimal definitions for assessing disease state in patients with psoriatic arthritis (PsA), and some of the commonly used definitions do not include assessment of skin lesions. We investigated the performance of various definitions in patients with PsA and psoriasis. METHODS: This was a posthoc analysis of data from the PRESTA study. The remission definitions analyzed were very low disease activity (VLDA) index, defined as 7/7 of the minimal disease activity (MDA) cutoffs; Disease Activity Index for PsA (DAPSA); and clinical (c-) DAPSA. The low disease activity (LDA) definitions analyzed were as follows: MDA defined as 5/7 cutoffs; MDA joint with both the tender joint count (TJC) and swollen joint count (SJC) cutoffs mandated; MDA skin where skin cutoff was mandated; MDA joint + skin where TJC, SJC, and skin cutoffs were mandated; DAPSA LDA; and cDAPSA LDA. RESULTS: At Week 24, the proportions of patients achieving VLDA, DAPSA, and cDAPSA remission were 10%, 35%, and 37%, respectively. Of the patients achieving DAPSA and cDAPSA remission, 55% and 56%, respectively, had Psoriasis Area and Severity Index > 1. The proportions of patients achieving MDA 5/7, MDA skin, MDA joint, and MDA joint + skin were 44%, 19%, 36%, and 14%, respectively, versus 70% achieving DAPSA and cDAPSA LDA. Notable residual levels of psoriasis were observed in patients achieving the definitions that did not require skin disease control. CONCLUSION: VLDA and MDA definitions are more stringent than DAPSA and cDAPSA definitions for the assessment of PsA. The relevance of residual disease to patients, however, remains to be determined. [Clinical Trial registration: ClinicalTrials.gov NCT00245960].

Relationship between beliefs about medicines, adherence to treatment, and disease activity in patients with rheumatoid arthritis under subcutaneous anti-TNFα therapy.

OBJECTIVE: In patients with rheumatoid arthritis (RA), nonadherence to treatment is often related to patients' beliefs and concerns regarding their medication. This study aimed to analyze the correlations regarding patients' medication beliefs, medication adherence, and objective measures of disease activity and safety in patients with RA established on subcutaneous (SC) anti-tumor necrosis factor α (TNFα) therapy. METHODS: This Phase IV, noninterventional, non-drug-specific study enrolled patients with RA being treated with stable-dose SC anti-TNFα (adalimumab, etanercept, golimumab, and certolizumab pegol). At initial visit and 6 and 12 months later, patients completed the Beliefs about Medicines Questionnaire-Specific section, assessing perceptions of personal need for anti-TNFα therapy (anti-TNFα-Necessity) and concerns (anti-TNFα-Concerns), Medication Adherence Rating Scale (MARS), mean Disease Activity Score in 28 joints (DAS28), and other scales. Longitudinal data were analyzed by linear mixed models. RESULTS: A total of 460 patients were included. At initial visit, anti-TNFα-Necessity beliefs were high (mean ± SD: 4.3 ± 0.55) vs anti-TNFα-Concerns (2.8 ± 0.78). Medication adherence (MARS) was high (4.8 ± 0.39). All scores remained stable over the 1-year follow-up period. Anti-TNFα-Necessity beliefs and anti-TNFα-Concerns were not related to each other, but strongly correlated with medication adherence. While concerns worsened with disease activity, clinical status, and low quality of life, necessity beliefs remained unaffected. CONCLUSION: In patients with RA established on stable-dose SC anti-TNFα, anti-TNFα-Necessity beliefs persistently outweighed anti-TNFα-Concerns, but both correlated with adherence. These findings may be of use in subsequent studies looking to predict adherence in patients starting treatment with SC anti-TNFα.

Effects of biologic disease-modifying anti-rheumatic drugs on the radiographic progression of rheumatoid arthritis: a systematic literature review.

OBJECTIVES: To evaluate the effect of biologic disease-modifying anti-rheumatic drugs (bDMARDs) on radiographic progression in patients with rheumatoid arthritis (RA). METHODS: A systematic review of electronic databases and conference proceedings was conducted through January 2015, to identify randomised controlled trials (RCTs) and observational studies that assessed the impact of bDMARDs [± conventional synthetic DMARDs (csDMARDs), mainly methotrexate (MTX)], versus csDMARDs alone, on radiographic progression in patients with RA. RESULTS: Following screening of >5000 records, 104 publications covering 63 studies were included. Of 34 RCTs in patients with early, active (n=13) or established RA (n=21) [abatacept (1, 2); adalimumab (4, 2); certolizumab pegol (1, 4); etanercept (3, 3); golimumab (1, 4); infliximab (1, 1); rituximab (1, 1); tocilizumab (1, 5)], combination therapy with a bDMARD and MTX had a significantly greater effect than placebo or MTX alone, in inhibiting radiographic progression. This included patients previously unresponsive, or who responded incompletely, to MTX treatment alone, and was supported by data from observational studies. Findings from a smaller subset of these and other RCTs supported superiority of combination therapy over bDMARD monotherapy, and bDMARD monotherapy over MTX, in slowing radiographic progression. CONCLUSIONS: There is evidence from RCTs with a range of bDMARDs that improvement in radiographic outcomes for patients with early or established RA, when used in combination with MTX and to a lesser extent as monotherapy, are significantly greater than MTX alone. There was no evidence of a difference between bDMARDs on inhibition of radiographic progression.

Contextual factors influence work outcomes in employed patients with ankylosing spondylitis starting etanercept: 2-year results from AS@Work.

Objectives: The aim was to determine changes over time in work outcomes and investigate the predictive value of baseline personal and work-related factors on the evolution of work outcomes among employed patients with AS initiating etanercept. Methods: Employment status, absenteeism and presenteeism were assessed using the Work Productivity and Activity Impairment for AS questionnaire in a 24-month open-label, observational study (NCT01421303). The potential effect of baseline factors on work outcomes was analysed using predictive modelling (Cox regression and linear mixed models). Results: After 24 months, 11/75 (14.7%) patients had permanently withdrawn from employment (seven because of AS). Absenteeism and presenteeism decreased significantly within 6 months of etanercept treatment and remained stable thereafter. Predictive modelling indicated that male sex (hazard ratio = 0.18; 95% CI: 0.04, 0.85), (log) number of working hours per week (hazard ratio = 0.13; 95% CI: 0.03, 0.51) and the possibility of developing skills (hazard ratio = 0.42; 95% CI: 0.19, 0.91) positively influenced time in employment. Over time, lower absenteeism was significantly associated with the quality of contact with colleagues [coefficient (s.e.): -0.35 (0.10)] and importance of the job for quality of life [-0.49 (0.17)], and higher absenteeism with current smoking [1.66 (0.44)] and change in job because of illness [1.51 (0.66)]. Over time, lower presenteeism was associated with male sex [-14.5 (2.64)], the possibility of postponing work [-6.60 (2.73)], quality of contact with colleagues [-2.04 (0.96)] and >50 workers in the company [-7.65 (2.76)], and higher presenteeism with manual profession [8.41 (2.72)]. Conclusion: Contextual factors influence work outcomes over time and should not be ignored when aiming to improve work outcomes in patients with AS. Trial registration: ClinicalTrials.gov, http://clinicaltrials.gov, NCT01421303.

Maintenance of remission and monotherapy status over 66 months in patients with psoriatic arthritis receiving etanercept.

OBJECTIVES: To determine if patients with psoriatic arthritis (PsA) who achieved remission within 6 months with etanercept (ETN) treatment (with or without methotrexate) were able to maintain remission over 66 months. Monotherapy status over the study duration was also monitored. METHODS: This was a post hoc analysis of PROVE (NCT00938015), a multicentre, observational study into the long-term adherence of ETN performed in rheumatology clinics in Belgium. To be included in PROVE, patients had active PsA and were either already receiving ETN treatment or had recently been prescribed it. Patients who achieved remission (defined as zero joints with synovitis) after 6 months of ETN treatment were monitored for maintenance of remission at each subsequent visit. In addition, patients on ETN monotherapy at Month 6 were observed. RESULTS: 303 patients participated and 156 (51.5%) patients completed 66 months of ETN treatment. The mean (standard deviation [SD]) disease duration was 7.5 (7.4) years and the majority had polyarticular-type PsA (87.1%). Overall, 142 patients achieved remission after 6 months of ETN treatment. Among the 83 patients who were in remission at Month 6 and remained in the study until the end, 72 (86.7%) were still in remission at Month 66. After 6 months, 66 patients were receiving ETN monotherapy and the majority continued with it until Month 66 (n=22/26; 84.6%). CONCLUSIONS: Within this patient population, remission was achieved quickly and was sustained in the long-term. Of those patients who were receiving monotherapy, most continued with this treatment strategy for the duration of the study.

An observational study of the real-life management of psoriasis patients treated with etanercept according to the new reimbursement criteria (in Belgium).

BACKGROUND: This study described the number of patients with psoriasis receiving flexible (continuous/intermittent) dosing with etanercept (ETN) and the real-world economic impact. METHODS: BeFlex was a prospective, observational study with a ≥1 year follow-up. Patients ≥18 years with moderate-to-severe psoriasis who were starting or re-starting treatment with ETN in alignment with Belgian reimbursement criteria were included. Cost of ETN was compared with cost of adalimumab, ustekinumab and infliximab using estimates from the National Institute for Sickness and Disability Insurance (INAMI/RIZIV). RESULTS: In the flexible-dosing cohort (n = 121 with dose-regimen data), 66% were treated continuously and 34% intermittently. Baseline characteristics were similar across dosing cohorts. In the per-protocol cohort (n = 138), average ETN treatment duration/year was 40 weeks; 43 weeks continuous and 33 weeks intermittent. The overall mean interruption duration was 3.9 weeks/treatment cycle; 0.2 week continuous and 11.1 weeks intermittent. Mean dose/year was 2065 mg; 2182 mg continuous and 1660 mg intermittent. Flexible ETN dosing reduced the cost by 20% versus INAMI/RIZIV estimates. The theoretical cost of the other continuously-dosed biologics was 28-44% higher than that of flexible ETN. CONCLUSION: Approximately one-third of Belgian patients received intermittent ETN treatment. Flexible ETN dosing was more cost-effective than treatment with biologic agents that require continuous dosing.

Treatment adherence, efficacy, and safety of etanercept in patients with active psoriatic arthritis and peripheral involvement in Belgium for 66 months (PROVE study).

OBJECTIVES: To describe the long-term adherence, efficacy, and safety in patients with psoriatic arthritis (PsA) treated with etanercept (ETN) in a daily clinical setting in Belgium. METHODS: The PROVE study was a prospective, multi-centre, open-label, observational study in patients with active PsA who had previously failed disease-modifying anti-rheumatic drugs. Patients were treated with ETN prescribed by their physician and adherence was monitored over 66 months. RESULTS: A total of 303 patients were enrolled (polyarticular-type n=264; oligoarticular-type n=39). 156 (51.5%) patients adhered to the treatment until the end of the study. The mean study duration was 4.0 (SD, 1.9) years. The most common reasons for discontinuing were non-response (35.9%), patient lost to follow-up (20.7%), and reasons unrelated to ETN (20.0%). Males adhered to treatment significantly longer than females (5.0 vs. 3.9 years; p<0.0001). After 6 months, 49.0% of patients with active synovitis at the start of the study had zero joints with synovitis, and this proportion increased to 77.6% by month 66 (p<0.001 for all time points vs. baseline). In polyarticular-type patients, the mean total Health Assessment Questionnaire (HAQ) score (0-60) decreased from 27.0 (95% CI 25.9-28.1) to 9.7 (8.5-10.9; 64.8% improvement; p<0.001) after 6 months and to 7.7 (6.2-9.3; 66.6% improvement; p<0.001) after 66 months. Treatment-related adverse events were reported in 177 (58.8%) of patients, and 53 (17.6%) patients reported serious adverse events related to treatment. CONCLUSIONS: In these patients with active PsA from daily clinical practice, adherence to ETN was high observed over 5.5 years and it was well tolerated.

Understanding limitations in at-work productivity in patients with active ankylosing spondylitis: the role of work-related contextual factors.

OBJECTIVE: To explore the effect of health-related and contextual factors on presenteeism, absenteeism, and overall work productivity loss in patients with active ankylosing spondylitis (AS). METHODS: Consecutive patients with AS starting their first tumor necrosis factor inhibitor and in paid employment were eligible. Patients completed the Work Productivity and Activity Impairment (WPAI) questionnaire for AS to assess presenteeism, absenteeism, and overall work productivity loss in the previous 7 days. In addition, they answered questions about work characteristics (type, characteristics of workplace, satisfaction of contacts with colleagues, and importance of work in life) and health status [Bath AS Functional Index (BASFI), AS Disease Activity Score-C-reactive protein (ASDAS-CRP)]. Physicians assessed the Bath Ankylosing Spondylitis Metrology Index, presence of articular and extraarticular manifestations, comorbidities, and laboratory indicators of inflammation. Stepwise regression models were computed to determine which work-related and health-related factors contributed to WPAI outcomes. RESULTS: The study included 80 patients. The WPAI presenteeism, absenteeism, and overall work productivity loss scores were 49.1%, 30.2%, and 53.1%, respectively. Presenteeism was associated with higher BASFI, female sex, and poor quality of contact with colleagues. Absenteeism was associated with increasing age, current smoking status, higher ASDAS-CRP, and low importance of work for life. Overall work productivity loss was associated with female sex, higher BASFI, past adaptation of job because of illness, number of working hours, and manual profession. CONCLUSION: Both health-related and contextual factors contribute to work limitations in patients with AS and suggest additional opportunities for improvement by addressing the working environment.