Estimating the response and economic burden of rheumatoid arthritis patients treated with biologic disease-modifying antirheumatic drugs in Taiwan using the National Health Insurance Research Database (NHIRD).

BACKGROUND: Previous studies in Taiwan utilizing the Taiwan's National Health Insurance Database (NHIRD) have estimated the direct healthcare costs of RA patients, but they have not focused on patients on bDMARDs, or considered patients' response to therapy. OBJECTIVES: The objective of this study was to estimate the rate of inadequate response for patients newly treated with biologic disease-modifying antirheumatic drugs (bDMARDs) as well as their costs and resource use. METHODS: Data were from the catastrophic illness file within the NHIRD from 1/1/2009 to 12/31/2013. Patients with RA, which was categorized by the presence of a catastrophic illness card, that were previously bDMARD-naïve, were included in this study if they initiated their first bDMARD during the index period. The index period included all of 2010, a pre-index period consisting of the index date- 365 days, and a follow-up period including the index date to 365 days post-index, were also included. Previously biologically-naïve patients were indexed into the study on the date of their first claim for a bDMARD. A validated algorithm was used to examine the rate of inadequate response (IR) in the biologically-naïve cohort of patients. Inadequate responders met one or more of the following criteria during their year of follow-up: low adherence (proportion of days covered <0.80); switched to or added a second bDMARD; added a new conventional synthetic DMARD (csDMARD); received ≥1 glucocorticoid injection; or increased oral glucocorticoid dosing. All-cause mean annual direct costs and resource use were measured in the year of follow-up. Costs were converted from NT$ to USD using 1 NT$ = 0.033 USD. RESULTS: A total of 818 patients with RA initiated their first bDMARD (54% etanercept and 46% adalimumab) in 2010. After one year of follow-up, 32% (n = 258) were classified as stable, 66% (n = 540) had an IR, and 2% (n = 20) were lost to follow-up. During the follow-up period mean annual total direct costs were $16,136 for stable patients compared to $14,154 for patients with IR. Mean annual non-medication direct costs were $937 for stable patients and $1,574 for patients with IR. Mean annual hospitalizations were higher for patients with IR (0.46) compared to stable patients (0.10) during the one year follow-up period. CONCLUSIONS: The majority of patients that were previously naïve to bDMARDs had an IR to their first bDMARD during the year of follow-up. Patients with an IR had numerically increased all-cause resource utilization and non-medication costs during the follow-up period compared to patients with stable disease. This level of IR suggests an unmet need in the RA treatment paradigm.

Examination of Patient-Reported Outcomes in Association with TNF-Inhibitor Treatment Response: Results from a US Observational Cohort Study.

INTRODUCTION: Implementation of a treat-to-target strategy is challenging when the patient and physician prioritize different goals. This study aimed to "translate" improvements in Clinical Disease Activity Index (CDAI) to concepts that resonate with patients (such as pain, fatigue, morning stiffness) by examining the association between changes in disease activity and patient-reported outcomes (PROs) in a national cohort of patients with rheumatoid arthritis (RA) initiating their first biologic treatment. METHODS: Patients in the Corrona registry with moderate or high disease activity (M/HDA) (defined by a CDAI score > 10), prior use of at least one conventional synthetic disease-modifying antirheumatic drug (csDMARD), 12-month follow-up, and initiating their first tumor necrosis factor inhibitor (TNFi) between 1 January 2006 through 1 November 2015 were identified. Patients were stratified on the basis of CDAI during follow-up, and changes in PROs were compared with a test of trend using CDAI-defined groups. RESULTS: Of 1570 patients, 37% achieved sustained remission or low disease activity (remission/LDA), 15% had improving remission/LDA, 12% had worsening M/HDA, and 35% were in sustained M/HDA during 12-month follow-up. Those in sustained remission/LDA had greater magnitude of improvement in physical functioning, pain, fatigue, morning stiffness, patient's global assessment, and quality of life compared with patients in sustained M/HDA (p < 0.001). CONCLUSION: Reduction in disease activity was associated with improvements in PROs, with the greatest improvements seen in those who achieved sustained remission/LDA. These results reinforce the benefits of a treat-to-target approach to RA care and may improve dialogue between patients and providers, support shared decision-making, and reduce "clinical inertia." FUNDING: Corrona, LLC.

Patient-reported outcomes from a randomised phase III study of baricitinib in patients with rheumatoid arthritis and an inadequate response to biological agents (RA-BEACON).

OBJECTIVES: To assess baricitinib on patient-reported outcomes (PROs) in patients with moderately to severely active rheumatoid arthritis, who had insufficient response or intolerance to ≥1 tumour necrosis factor inhibitors (TNFis) or other biological disease-modifying antirheumatic drugs (bDMARDs). METHODS: In this double-blind phase III study, patients were randomised to once-daily placebo or baricitinib 2 or 4 mg for 24 weeks. PROs included the Short Form-36, EuroQol 5-D, Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Health Assessment Questionnaire-Disability Index (HAQ-DI), Patient's Global Assessment of Disease Activity (PtGA), patient's assessment of pain, duration of morning joint stiffness (MJS) and Work Productivity and Activity Impairment Questionnaire-Rheumatoid Arthritis. Treatment comparisons were performed with logistic regression for categorical measures or analysis of covariance for continuous variables. RESULTS: 527 patients were randomised (placebo, 176; baricitinib 2 mg, 174; baricitinib 4 mg, 177). Both baricitinib-treated groups showed statistically significant improvements versus placebo in most PROs. Improvements were generally more rapid and of greater magnitude for patients receiving baricitinib 4 mg than 2 mg and were maintained to week 24. At week 24, more baricitinib-treated patients versus placebo-treated patients reported normal physical functioning (HAQ-DI <0.5; p≤0.001), reductions in fatigue (FACIT-F ≥3.56; p≤0.05), improvements in PtGA (p≤0.001) and pain (p≤0.001) and reductions in duration of MJS (p<0.01). CONCLUSIONS: Baricitinib improved most PROs through 24 weeks compared with placebo in this study of treatment-refractory patients with previously inadequate responses to bDMARDs, including at least one TNFi. PRO results aligned with clinical efficacy data for baricitinib. TRIAL REGISTRATION NUMBER: NCT01721044; Results.

Increased healthcare resource utilization in higher disease activity levels in initiators of TNF inhibitors among US rheumatoid arthritis patients.

OBJECTIVE: Determine healthcare resource utilization (HCRU) in biologic-naïve initiators of TNF inhibitors (TNFis) associated with their disease activity from a national cohort of rheumatoid arthritis (RA) patients. METHODS: RA patients were identified at their first TNFi initiation (index date) in the Corrona registry. Patients with age of RA onset <18, comorbid psoriasis/psoriatic arthritis, fibromyalgia, or osteoarthritis were excluded. Patients were categorized into disease activity (DA) strata by the lowest level of DA (and sustaining low levels for at least two visits) using the Clinical Disease Activity Index (CDAI) across all visits in Corrona while on a TNFi during 1 year after initiation. Rates of all-cause and RA-related hospitalizations, rheumatologist visits, and joint surgeries while on TNFi therapy were reported and compared across DA levels along with the incidence rate ratio (IRR) adjusted for age, gender, and RA duration using Poisson mixed models. RESULTS: Of 1931 RA patients: 15% achieved sustained remission, 22% remission, 14% sustained low DA, 23% low DA and 27% moderate/high DA (M/HDA). Those in M/HDA had statistically higher rates of hospitalizations (37.3 per 100 patient years (py), 95% CI: 31.6-43.7 and joint surgeries (20.8 per 100 py, 95% CI: 16.6-25.8) compared to the sustained remission cohort, resulting in respective IRRs of 2.3 (p < 0.001) and 1.7 (p = 0.046). CONCLUSION: Many biologic naïve RA patients initiating TNFi failed to achieve sustained remission during a 1 year period while remaining on TNFi therapy. Patients in higher DA levels had higher HCRU rates vs. patients in sustained remission, suggesting that achieving treat-to-target goals would reduce health care expenses.

Comparative effects of raloxifene and alendronate on fracture outcomes in postmenopausal women with low bone mass.

UNLABELLED: The double-blind, randomized raloxifene alendronate comparison trial was the first study designed to compare two osteoporosis therapies head-to-head for fracture risk reduction. The original protocol planned to treat 3000 postmenopausal women with alendronate 10 mg/day (ALN) or raloxifene 60 mg/day (RLX) for 5 years, and to recruit women (50-80 years old) with a femoral neck bone mineral density (BMD) T-score between -2.5 and -4.0, inclusive, no prevalent vertebral fractures, and no prior bone-active agent use. The trial was stopped early, due to difficulty in finding treatment-naïve women to meet enrollment goals within the planned timeline, resulting in insufficient power to show non-inferiority between therapies in the primary endpoint (number of women with >or=1 new osteoporotic vertebral or nonvertebral fracture). Except for vertebral fractures, fracture analyses were based upon 1412 of the 1423 women randomized (mean age of 66 years). After 312+/-254 days (mean+/-SD), 22 women in the ALN group and 20 in the RLX group had new vertebral or nonvertebral fractures. Four women in the ALN group and none in the RLX group had moderate/severe vertebral fractures, a pre-specified endpoint (P=0.04). Lumbar spine, femoral neck, and total hip BMD were increased from baseline at 2 years in each group (P<0.001), with greater increases in the ALN group (each P<0.05). Similar numbers of women in each group had >or=1 adverse event and discontinued due to an adverse event. The only adverse events with an incidence that differed between groups were colonoscopy, diarrhea, and nausea; each was more common with ALN treatment (each P<0.05). One woman in each group had a venous thromboembolic event. One case of breast cancer occurred in each group. In summary, as this trial was terminated early, there was insufficient power to compare the fracture risks between alendronate and raloxifene. Safety profiles were as expected from clinical trial and post-marketing reports. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT00035971.