Real-world evaluation of TNF-inhibitor utilization in rheumatoid arthritis.

OBJECTIVES: To evaluate 12-month treatment patterns, healthcare resource use (HCRU), and costs for patients with rheumatoid arthritis (RA), following initiation of index TNF inhibitors (TNFi) and subsequent biologic DMARDs (bDMARDs). METHODS: This was a retrospective cohort analysis of adults with RA newly initiating TNFi in the Truven Marketscan Commercial Claims and Encounters and Medicare Supplemental Databases during 2010-2013. A sub-group of patients who switched to a bDMARD within 12 months post-index and within 180 days of last index TNFi were subsequently evaluated over 12 months. TNFi/bDMARD treatment patterns were characterized as: continuers, no gap >180 days in prescription/administration of index TNFi; discontinuers, gap >180 days; switchers, initiated new bDMARD. Concomitant conventional synthetic DMARD use, co-morbid chronic illnesses, and RA severity were assessed. All-cause/RA-related HCRU and costs were evaluated 12 months post-index. RESULTS: Of 9567 identified patients, 67.2%, 17.3%, and 15.4% were continuers, discontinuers, and switchers, respectively. Switchers had the highest 12-month unadjusted mean all-cause costs of $34,585 vs $33,051 for continuers (p = 0.1158) and $24,915 for discontinuers (p < 0.0001; discontinuers vs continuers, p < 0.0001). RA-related costs comprised 82.8%, 31.4%, and 85.7% of total costs for continuers, discontinuers, and switchers, respectively. Of 764 switchers, 68.2% switched to alternative TNFi (cyclers), the rest to non-TNFi bDMARDs; 36.7% of patients who switched to TNFi switched again (to third-line bDMARD) vs 27.6% (p = 0.0313) of those who switched to non-TNFi bDMARDs. Switchers to non-TNFi bDMARDs had higher mean 12-month all-cause costs of $76,580 compared with $50,689 for switchers to alternative TNFi (p < 0.0001); biologic-administration visits comprised 78.8% of the greater total RA-related costs of switchers to non-TNFi bDMARDs. CONCLUSIONS: Real-world TNFi discontinuation/switching rates correspond to randomized controlled trial non-response rates. TNFi cycling is common and associated with an increased likelihood of switching to third-line bDMARD. Switching to non-TNFi bDMARDs was associated with higher costs, mostly attributed to in-office administrations.

Model-based drug development: a rational approach to efficiently accelerate drug development.

The pharmaceutical industry continues to face significant challenges. Very few compounds that enter development reach the marketplace, and the investment required for each success can surpass $1.8 billion. Despite attempts to improve efficiency and increase productivity, total investment continues to rise whereas the output of new medicines declines. With costs increasing exponentially through each development phase, it is failure in phase II and phase III that is most wasteful. In today's development paradigm, late-stage failure is principally a result of insufficient efficacy. This is manifested as either a failure to differentiate sufficiently from placebo (shown for both novel and precedented mechanisms) or a failure to demonstrate sufficient differentiation from existing compounds. Set in this context, this article will discuss the role model-based drug development (MBDD) approaches can and do play in accelerating and optimizing compound development strategies through a series of illustrative examples.

Improved pain, physical functioning and health status in patients with rheumatoid arthritis treated with CP-690,550, an orally active Janus kinase (JAK) inhibitor: results from a randomised, double-blind, placebo-controlled trial.

OBJECTIVES: To determine the efficacy of CP-690,550 in improving pain, function and health status in patients with moderate to severe active rheumatoid arthritis (RA) and an inadequate response to methotrexate or a tumour necrosis factor alpha inhibitor. METHODS: Patients were randomised equally to placebo, CP-690,550 5, 15 or 30 mg twice daily for 6 weeks, with 6 weeks' follow-up. The patient's assessment of arthritis pain (pain), patient's assessment of disease activity, Health Assessment Questionnaire-Disability Index (HAQ-DI) and Short Form-36 (SF-36) were recorded. RESULTS: At week 6, significantly more patients in the CP-690,550 5, 15 and 30 mg twice-daily groups experienced a 50% improvement in pain compared with placebo (44%, 66%, 78% and 14%, respectively), clinically meaningful reductions in HAQ-DI (> or =0.3 units) (57%, 75%, 76% and 36%, respectively) and clinically meaningful improvements in SF-36 domains and physical and mental components. CONCLUSIONS: CP-690,550 was efficacious in improving the pain, function and health status of patients with RA, from week 1 to week 6.

Oral granisetron for the prevention of acute late onset nausea and vomiting in patients treated with moderately emetogenic chemotherapy.

PURPOSE: To demonstrate the efficacy of oral granisetron 1 mg twice daily for the prevention of late onset nausea and vomiting after moderately emetogenic chemotherapy that includes cyclophosphamide, carboplatin, or doxorubicin. METHODS: Prior to chemotherapy, patients were stratified by gender and randomized to receive oral granisetron (1 mg tablet twice daily) or prochlorperazine (10 mg sustained release capsule twice daily). Study agents were administered 1 h prior to and 12 h after chemotherapy. Antiemetics were administered for seven consecutive days. Efficacy variables were assessed 48 and 72 h after administration of chemotherapy, and included no emesis, no nausea, no moderate or severe nausea, and no antiemetic rescue. Safety analysis included all patients who received medication. RESULTS: A total of 230 patients were included in the intent-to-treat analysis; 119 patients received granisetron and 111 patients received prochlorperazine. Females, and all patients combined, who received granisetron had significantly higher no-emesis rates at 48 h (p =.010 and p =.016, respectively) than patients who received prochlorperazine. No-nausea rates at 48 h were numerically higher for all patients combined and females who received granisetron rather than prochlorperazine. Response rates for no nausea or mild nausea were also numerically higher in females treated with granisetron, compared to prochlorperazine, at 48 h. Significantly more patients (p <.001) and females (p <.001) in the granisetron group than in the prochlorperazine group did not require rescue antiemetics at 48 h. At 72 h, efficacy results were comparable for granisetron and prochlorperazine. CONCLUSION: Oral granisetron is well tolerated and more effective than prochlorperazine in preventing nausea and vomiting for up to 48 h following treatment with moderately emetogenic chemotherapy.

Ethnic differences in anthropometric characteristics of young children and their parents.

The distribution of body fat, or fat patterning, is an important risk factor for cardiovascular disease and diabetes, independent of obesity. Furthermore, the incidence of cardiovascular disease and diabetes varies by ethnicity. We documented ethnic differences in anthropometric characteristics and body fat distribution between Anglo, Black, and Mexican American men (n = 101), women (n = 245), boys (n = 111), and girls (n = 111). We used aggregates of skinfold measures to examine ethnic differences in the deposition of fat in body compartments (body, trunk, leg, and arm) and analyzed trunk-extremity skinfold ratios to determine which best reflected ethnic differences in fat distribution. The results show that Mexican American mothers have larger skinfold ratios and more body fat (as determined by skinfold aggregates) than either Anglo or Black American mothers, whereas Black American mothers have larger ratios than Anglo American mothers. Mexican American fathers also have larger skinfold ratios but not more body fat (skinfold aggregates) than Anglo American fathers. Mexican American fathers have more body fat than Black American fathers, but we found no differences between skinfold ratios. The ethnic differences among children in skinfold ratios and aggregates are similar to those found among fathers, with more differences among girls than boys. Fat patterning differences do exist among the three ethnicities, with greater trunk fat among Mexican and Black Americans. Those ethnicities are known to be at higher risk for cardiovascular disease and diabetes.