This study showed that osteonecrosis in rabbits is chronologically associated with changes in neural factors.

Background Treatment paradigms for rheumatoid arthritis (RA) continue to evolve with the generation of further efficacy and safety evidence and the launch of new biologics and novel oral treatments. Population-based studies can help assess which strategies are being used in “real-world” practice for the complete spectrum of clinical RA. This approach can also relate therapy to the consumption of other health-care resources such as RA-related surgery or hospitalization which are fundamental for RA economic models. Objectives To describe biologics use in RA patients newly diagnosed in 2009 followed for two years. Methods A retrospective cohort analysis of adults (age ≥20) with complete medical and pharmacy insurance claims from 1 January 2008 to 31 December 2011 was deployed. “Incident RA” required a primary diagnosis at two separate visits 30 days apart in 2009 and no prior claims for RA. Databases used were the Marketscan Commercial Claims and Encounters (CCAE) and Medicare Supplemental and Coordination of Benefits (MSCB) databases from Truven Health Analytics. Information on demographics, co-morbidities and treatments including conventional (cDMARD) and biologic (bDMARD) therapy and sequencing thereof was obtained for the entire follow-up period. Time to discontinuation and Medication Possession Ratios (MPR), were calculated; a cut-point of 80% was considered to be good adherence. Results This analysis is based on 8,507 incident cases arising from 8.02 million persons who met study criteria. In the first 60 days after diagnosis, 42% of patients received no DMARD therapy; 7.6% initiated a biologic and the remainder a cDMARD; median time to first prescription overall was 7 days. Over the first 12 months, 26% of patients received no DMARD therapy; 64.2% initiated cDMARDs, and 9.7% initiated bDMARDs either as monotherapy (4.3%) or in combination with cDMARDs (5.4%). More than 90% of the latter two groups involved TNF-inhibitors; abatacept was the most common other biologic. By the end of follow-up, 23% of patients had been prescribed at least one biologic and switching to a second occurred in 22% of starters. However, 10% of patients prescribed a biologic filled only one prescription and, within six months, 26% had discontinued therapy; after that, the rate of discontinuation slowed such that by 24 months, 64% were under active treatment. In those receiving biologics, the proportion with MPRs >80% was 72% in year 1 and 77% in year 2, and was consistent across specific drugs. Conclusions A quarter of newly diagnosed patients did not receive any DMARD over two years. Of those that did, the majority began with cDMARD but, by the end of follow-up, the most commonly used drugs were MTX and TNF-inhibitors, and over one-fifth of patients had been prescribed biologics. After steep initial reductions, biologic use was stable as reflected in the time to discontinuation. bDMARD choices were limited for this cohort compared with later cohorts as in 2009 golimumab and certolizumab pegol had just been launched in the US,...