Effects of BI 655064, an antagonistic anti-CD40 antibody, on clinical and biomarker variables in patients with active rheumatoid arthritis: a randomised, double-blind, placebo-controlled, phase IIa study.

OBJECTIVE: To evaluate the safety, efficacy and therapeutic mechanism of BI 655064, an antagonistic anti-CD40 monoclonal antibody, in patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX-IR). METHODS: In total, 67 patients were randomised to receive weekly subcutaneous doses of 120 mg BI 655064 (n=44) or placebo (n=23) for 12 weeks. The primary endpoint was the proportion of patients who achieved 20% improvement in American College of Rheumatology criteria (ACR20) at week 12. Safety was assessed in patients who received at least one dose of study drug. RESULTS: At week 12, the primary endpoint was not met, with 68.2% of patients treated with BI 655064 achieving an ACR20 vs 45.5% with placebo (p=0.064); using Bayesian analysis, the posterior probability of seeing a difference greater than 35% was 42.9%. BI 655064 was associated with greater changes in CD40-CD40L pathway-related markers, including reductions in inflammatory and bone resorption markers (interleukin-6, matrix metalloproteinase-3, receptor activator of nuclear factor-κB ligand), concentration of autoantibodies (immunoglobulin [Ig]G rheumatoid factor [RF], IgM RF, IgA RF) and CD95+ activated B-cell subsets. No serious adverse events (AEs) related to BI 655064 treatment or thromboembolic events occurred; reported AEs were mainly of mild intensity. CONCLUSION: Although blockade of the CD40-CD40L pathway with BI 655064 in MTX-IR patients with RA resulted in marked changes in clinical and biological parameters, including reductions in activated B-cells, autoantibody production and inflammatory and bone resorption markers, with a favourable safety profile, clinical efficacy was not demonstrated in this small phase IIa study. TRIAL REGISTRATION NUMBER: NCT01751776.

The economic burden of the ankylosing spondylitis in the Czech Republic: comparison between 2005 and 2008.

To investigate the burden of ankylosing spondylitis in the Czech Republic as a baseline for future health economic evaluations. Data were obtained from two cross-sectional studies Beda I (2005) and Beda II (2008), performed in 1,008 and 509 patients, respectively. Methodology used was Cost-of-Illness prevalence-based analysis bottom-up approach. Analysis was performed from payer (health insurance companies) and societal perspective (including productivity costs using friction cost approach). Mean age of sample in Beda I and Beda II was 50.2 and 52.5 years, male were present by 61.0 and 62.7 %; average disease duration was 23.0 and 26.4 years, respectively. Mean total annual costs per patient in the sample were €4,782 in Beda I and €5806 in Beda II. Average direct costs per patient in the sample per year are estimated at €1,812 (Beda I) and €2,588 (Beda II) with the average productivity costs €2,970 (Beda I) and €3,218 (Beda II). We observed a small decrement in percentage (6.7 %) of productivity costs for Beda II as an influence of higher consumption of biologic drugs, hence higher direct costs and possible productivity preservation. The largest direct cost burdens were spa procedures (45.3 %, Beda I) and biological drugs (52.8 %, Beda II). Unique analysis of the burden of the AS in the Central-Eastern Europe presents health care resource and cost consumption by comparing two cross-sectional prevalence-based studies. Further analysis should be carried to obtain data connecting health status with costs consumption in order to analyse the AS from this perspective.

Work Productivity and Costs Related to Patients with Ankylosing Spondylitis, Rheumatoid Arthritis, and Psoriasis.

OBJECTIVES: To determine and compare the impact of rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriasis on work productivity, to calculate the productivity costs (PC), and to map out factors that influence (functional status and disease activity) work productivity. METHODS: The Work Productivity and Activity Impairment questionnaire was used to evaluate productivity losses of patients with RA (n = 77), AS (n = 230), and psoriasis (n = 93). Demographic data, patient-reported outcomes (PROs) (Health Assessment Questionnaire [HAQ] and Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]), and clinical parameters (Disease Activity Score in 28 joints [DAS28], body surface area [BSA], and Psoriasis Area and Severity Index [PASI]) were collected. The correlations among PROs, clinical parameters, and overall productivity loss were examined, and multiple regression models were used to examine relationships among parameters and productivity loss. PC were calculated using the friction cost approach. RESULTS: Mean patient age and disease duration were 47.1 and 15.7 years, respectively. The mean HAQ and DAS28 in patients with RA were 1.22 and 5.6, respectively. The mean BASDAI score in patients with AS was 4.43. The mean BSA and PASI score in patients with psoriasis were 21.1% and 12.9, respectively. The percentage of patients with psoriatic arthritis (in those with psoriasis) was 24.7%. We did not find significant differences in Work Productivity and Activity Impairment domains among various diagnoses. Patients with AS, RA, and psoriasis reported overall work productivity losses of 40.9%, 42.9%, and 42.8%, respectively. Daily activity impairments were approximately 50.0%. Overall work productivity loss strongly correlated with PROs, whereas correlations with clinical parameters were weak. The HAQ and BASDAI were identified as major predictors of productivity impairment. CONCLUSIONS: The greatest loss in productivity was in those with psoriatic arthritis; however, it was not significant. In contrast to clinical parameters (DAS28, BSA, and PASI score), PROs (HAQ and BASDAI score) significantly influence loss of productivity. The average annual lost PC per patient was estimated to be €2000.

Medical and Productivity Costs of Rheumatoid Arthritis in The Czech Republic: Cost-of-Illness Study Based on Disease Severity.

OBJECTIVE: International pharmacoeconomic studies suggest that functional impairment can be a significant predictor for the evaluation of direct and productivity costs for rheumatoid arthritis (RA). We calculated the direct and productivity costs for five Health Assessment Questionnaire (HAQ) groups of patients (HAQ scores <0.6, 0.6 ≥ 1.1, 1.1 ≥ 1.6, 1.6 ≥ 2.1, and ≥2.1) in the Czech Republic. METHODS: This was a retrospective cross-sectional study. We included 261 patients with RA, aged 18 to 84 years. We applied a bottom-up method by retrospectively reviewing individual patient medical records. Patients' demographic characteristics, patient-reported outcome, and clinical parameters were gathered at the time of data collection. For the calculation of productivity costs, we used the friction cost approach, based on patient absenteeism with a friction period of 130 workdays, with average monthly income used as the denominator. Costs were expressed as a mean value per patient with RA in each HAQ group. RESULTS: Mean patient age was 56.4 years. average time from diagnosis was 14.5 years, the mean HAQ score was 1.15, and the Disease Activity Score in 28 joints was 3.45. A total of 47.5% patients were treated with biologics. Mean annual direct medical costs for each HAQ group were €5315, €7357, €7697, €7716, and €8968, respectively. The mean annual indirect costs associated with productivity loss were €1414, €1459, €1610, €1876, and €2307, respectively. CONCLUSIONS: Direct costs and productivity costs for patients with RA are closely related to the value of the HAQ score. The annual mean total (direct plus productivity) costs per patient 1) treated with biologics, 2) without biologic treatment, and 3) from the overall cohort were €14,763, €3,559, and €8,882, respectively.