Mixed treatment comparison of the treatment discontinuations of biologic disease-modifying antirheumatic drugs in adults with rheumatoid arthritis.

BACKGROUND: Introduction of biologic disease-modifying antirheumatic drugs (DMARDs) has considerably changed treatment options for rheumatoid arthritis (RA) over the past decade. Very little information is available on comparative discontinuation rates of the biologics. OBJECTIVE: To compare treatment discontinuations for 9 biologic DMARDs in adults with RA. METHODS: We searched electronic databases through May 2012 to retrieve randomized controlled trials (RCTs) of patients with RA that compared biologic DMARDs with placebo or another biologic DMARD. The primary outcome was treatment discontinuation during the blinded phase of the trials, measured as overall withdrawals, withdrawals resulting from lack of efficacy, and withdrawals resulting from adverse events. Random-effects meta-analysis estimated the effect size for individual agents, and adjusted indirect comparisons were made between biologics using mixed treatment comparisons (MTC) meta-analysis. RESULTS: Forty-four trials were included in the analysis. In comparison with placebo, biologics were less likely to be withdrawn because of lack of efficacy (OR 0.22, 95% CI 0.17 to 0.27) and more likely to be withdrawn because of an adverse event (OR 1.41, 95% CI 1.16 to 1.70). Based on the MTC, certolizumab had the most favorable overall withdrawal profile, followed by etanercept and rituximab. Certolizumab had lower relative withdrawal rates resulting from lack of efficacy than adalimumab, anakinra, and infliximab. Anakinra had higher relative withdrawal rates resulting from lack of efficacy than most other biologics. Certolizumab and infliximab had more, while etanercept had fewer, withdrawals because of adverse events than most other drugs. CONCLUSIONS: Based on MTC using data from RCTs, differences in discontinuation rates were observed, generally favoring certolizumab, etanercept, and rituximab over other biologic DMARDs. These potential differences need to be further explored in head-to-head trials or well-conducted observational studies.

Impact of the 2002 American society for Colposcopy and Cervical Pathology guidelines on cervical cancer diagnosis in a geographically diverse population of commercially insured women, 1999-2004.

OBJECTIVE: To report the impact of the release of the 2002 American Society for Colposcopy and Cervical Pathology guidelines on the management of abnormal cytological findings on time to diagnosis of cervical cancer in an insured population. METHODS: This retrospective study identified women with cervical cancer (invasive and carcinoma in situ) through commercially insured administrative claims data. The cervical cancer case definition required a claim for cervical cancer and a claim with a diagnostic procedure (colposcopy, conization, biopsy, or hysterectomy). Time to diagnosis was defined as days between the initial Pap screening and the diagnostic procedure. RESULTS: Between 1999 and 2004, there were 3,325 women aged 18 to 64 years who met the case definition for cervical cancer. Median time to diagnosis decreased from 42 days (interquartile range = 23-93 d) to 36.5 days (interquartile range = 20.5-80 d) for women with invasive cancer after the guideline change. The number of follow-up Pap screenings before biopsy also decreased (p = .0067). Among women with carcinoma in situ whose initial Pap screening was completed by a family practice clinician, time to diagnosis was projected to be more than 9 days longer compared with those whose screening was performed by a gynecologist. CONCLUSIONS: The 2002 American Society for Colposcopy and Cervical Pathology guidelines for the management of abnormal cytological findings seem to have had a positive impact on the time to diagnosis and Pap screening use before biopsy for women diagnosed with cervical cancer.

The influence of UGT polymorphisms as biomarkers in solid organ transplantation.

In solid organ transplant patients, it is important to maintain a fine balance between preventing rejection and reducing adverse effects. Several immunosuppressive agents such tacrolimus, cyclosporine, sirolimus and everolimus require therapeutic drug monitoring. The study of germline variation of the genome has opened novel opportunities to individualize therapy. Among the currently available immunosuppressive agents, cyclosporine, tacrolimus and mycophenolic acid are in vitro substrates of the UGT1A and 2B families of glucuronidation enzymes. Mycophenolic acid, either given as mycophenolate mofetil or mycophenolate sodium, is the most frequently used antiproliferative immunosuppressant. Mycophenolic acid is a prodrug which is rapidly de-esterified in the gut wall, blood, liver and tissue to the active moiety, mycophenolic acid (MPA). MPA undergoes significant hepatic metabolism to several metabolites. The 7-hydroxyglucuronide MPA is the major metabolite and is inactive. This paper reviews the current status of the genetic associations between germline UGT variants and the pharmacokinetics and pharmacodynamics of mycophenolic acid. Our conclusive assessment of the studies conducted so far is that these germline markers are not ready to be used in the clinic to individualize mycophenolic acid dosing and improve outcome. Novel approaches are required to identify new genetic determinants of outcomes in transplantation.

Closing the quality gap: revisiting the state of the science (vol. 4: medication adherence interventions: comparative effectiveness).

OBJECTIVES: To assess the effectiveness of patient, provider, and systems interventions (Key Question [KQ] 1) or policy interventions (KQ 2) in improving medication adherence for an array of chronic health conditions. For interventions that are effective in improving adherence, we then assessed their effectiveness in improving health, health care utilization, and adverse events. DATA SOURCES: MEDLINE®, the Cochrane Library. Additional studies were identified from reference lists and technical experts. REVIEW METHODS: Two people independently selected, extracted data from, and rated the risk of bias of relevant trials and systematic reviews. We synthesized the evidence for effectiveness separately for each clinical condition, and within each condition, by type of intervention. We also evaluated the prevalence of intervention components across clinical conditions and the effectiveness of interventions for a range of vulnerable populations. Two reviewers graded the strength of evidence using established criteria. RESULTS: We found a total of 62 eligible studies (58 trials and 4 observational studies) from our review of 3,979 abstracts. These studies included patients with diabetes, hyperlipidemia, hypertension, heart failure, myocardial infarction, asthma, depression, glaucoma, multiple sclerosis, musculoskeletal diseases, and multiple chronic conditions. Fifty-seven trials of patient, provider, or systems interventions (KQ 1) evaluated 20 different types of interventions; 4 observational studies and one trial of policy interventions (KQ 2) evaluated the effect of reduced out-of-pocket expenses or improved prescription drug coverage. We found the most consistent evidence of improvement in medication adherence for interventions to reduce out-of-pocket expenses or improve prescription drug coverage, case management, and educational interventions across clinical conditions. Within clinical conditions, we found the strongest support for self-management of medications for short-term improvement in adherence for asthma patients; collaborative care or case management programs for short-term improvement of adherence and to improve symptoms for patients taking depression medications; and pharmacist-led approaches for hypertensive patients to improve systolic blood pressure. CONCLUSIONS: Diverse interventions offer promising approaches to improving medication adherence for chronic conditions, particularly for the short term. Evidence on whether these approaches have broad applicability for clinical conditions and populations is limited, as is evidence regarding long-term medication adherence or health outcomes.

Non-contact respiratory rate measurement validation for hospitalized patients.

This paper presents the first clinical results for validating the accuracy of respiratory rate obtained for hospitalized patients using a non-contact, low power 2.4 GHz Doppler radar system. Twenty-four patients were measured in this study. The respiratory rate accuracy was benchmarked against the respiratory rate obtained using Welch Allyn Propaq Encore model 242, the Embla Embletta system with Universal XactTrace respiratory effort sensor and Somnologica for Embletta software, and by counting chest excursions. The 95% limits of agreement between the Doppler radar and reference measurements fall within +/-5 breaths per minute.