Do Biologic Therapies for Rheumatoid Arthritis Offset Treatment-Related Resource Utilization and Cost? A Review of the Literature and an Instrumental Variable Analysis.

PURPOSE OF REVIEW: One justification for using expensive biologic therapy in rheumatoid arthritis (RA) has been that it can reduce future healthcare utilization such as joint surgeries and physician visits. However, the evidence to support this assertion is unclear. We conducted a review of the literature for studies which have analyzed the trends in resource use of RA patients, and then undertook a retrospective observational analysis of a Canadian administrative database using instrumental variable methods. RECENT FINDINGS: Our review found a trend in reduced resource utilization prior to the introduction of biologics and no evidence that biologic therapies have specifically contributed to this reduction. Our observational analysis, which overcame some of the epidemiological challenges with determining the influence of biologics on resource utilization, found a possible reduction in other medications but possible increases rather than decreases in physician visits and hospitalizations. However, our sample was not sufficiently large to make definitive conclusions. Over 15 years since the introduction of biologics for RA, no evidence exists supporting the assumption that biologic therapies reduce future healthcare utilization. While such a question is challenging to generate evidence for, and so an absence of evidence does not suggest that the hypothesis is incorrect, an instrumental variable analysis using sufficient data could provide definitive evidence.

Incentives in Rheumatology: the Potential Contribution of Physician Responses to Financial Incentives, Public Reporting, and Treatment Guidelines to Health Care Sustainability.

Concerns about the sustainability of current health care expenditure are focusing attention on the cost, quality and value of health care provision. Financial incentives, for example pay-for-performance (P4P), seek to reward quality and value in health care provision. There has long been an expectation that P4P schemes are coming to rheumatology. We review the available evidence about the use of incentives in this setting and provide two emerging examples of P4P schemes which may shape the future of service provision in rheumatology. Currently, there is limited and equivocal evidence in rheumatology about the impact of incentive schemes. However, reporting variation in the quality and provision of rheumatology services has highlighted examples of inefficiencies in the delivery of care. If financial incentives can improve the delivery of timely and appropriate care for rheumatology patients, then they may have an important role to play in the sustainability of health care provision.

Treatment and comorbidity burden among people living with HIV: a review of systematic literature reviews.

Background: As the human immunodeficiency virus (HIV) treatment landscape continues to evolve, the prolonged life expectancy and long-term exposure to antiretroviral drugs have modified the burden associated with living with HIV. Objective: To better understand the current treatment and comorbidity burden in people living with HIV (PLWH). Methods: Peer-reviewed systematic literature reviews (SLRs) between 2017 and 2020 that included US studies and examined drug adherence/pill burden, resistance burden, or comorbidities in PLWH were identified. Methods and findings were extracted for the overall studies and examined in the subset of US studies. Results: Among 665 publications identified, 47 met the inclusion criteria (drug adherence/pill burden: 5; resistance: 3; comorbidities: 40). While antiretroviral drug adherence levels varied across SLRs, single-tablet regimens (STR) were associated with higher adherence versus multiple-tablet regimens. STRs were also associated with lower risk of treatment discontinuation, higher cost-effectiveness, and lower risk of hospitalization. Longer survival resulted in a high comorbidity burden, with non-AIDS causes accounting for 47% of deaths among PLWH in the US. HIV doubled the risk of cardiovascular disease and was associated with other health problems, including bone and muscle diseases, depression, and cancers. Several antiretroviral regimens were associated with chronic diseases, including cardiometabolic conditions. Lifetime HIV costs are substantially increasing, driven by antiretroviral, adverse event, and comorbidity treatment costs cumulated due to longer survival times. Conclusions: There is a considerable burden associated with HIV and antiretroviral treatment, highlighting the benefits of less complex and safer regimens, and the unmet need for effective preventative interventions.

Healthcare Resource Utilization and Costs in Patients with EGFR-Mutated Advanced Non-Small Cell Lung Cancer Receiving First-Line Treatment in the United States: An Insurance Claims-Based Descriptive Analysis.

BACKGROUND: An estimated 10-15% of non-small cell lung cancer (NSCLC) cases present with epidermal growth factor receptor mutation (EGFRm). While EGFR tyrosine kinase inhibitors (EGFR-TKIs) such as osimertinib have become first-line (1L) standard of care for these patients, limited chemotherapy use still occurs in real-world practice. Studies of healthcare resource use (HRU) and cost of care provide a means by which the value of various treatment regimens, healthcare efficiency, and disease burden can be assessed. These studies are important for population health decision makers and health systems that prioritize value-based care to drive population health. OBJECTIVE: The aim of this study was to descriptively assess HRU and costs among patients with EGFRm advanced NSCLC initiating 1L therapy in the United States. METHODS: IBM MarketScan Research Databases (January 1, 2017 to April 30, 2020) were used to identify adult patients with advanced NSCLC, based on a diagnosis for lung cancer (LC) and initiation of 1L therapy or diagnosis of metastases within 30 days of the first LC diagnosis. All patients had ≥ 12 months of continuous insurance eligibility prior to the first LC diagnosis and initiated (in 2018 or after) an EGFR-TKI during any line of therapy to proxy EGFRm status. Per-patient-per-month all-cause HRU and costs were described during 1L for patients initiating 1L osimertinib or chemotherapy. RESULTS: A total of 213 patients with advanced EGFRm NSCLC were identified (mean age at 1L initiation: 60.9 years; 69.0% female). In 1L, 66.2% initiated osimertinib, 21.1% chemotherapy, and 12.7% another regimen. Mean 1L therapy duration was 8.8 months (osimertinib) and 7.6 months (chemotherapy), respectively. Among osimertinib recipients, 28% had an inpatient admission, 40% an emergency room (ER) visit, and 99% an outpatient visit. Among chemotherapy recipients, these proportions were 22%, 31%, and 100%. Mean monthly all-cause healthcare costs among osimertinib and chemotherapy patients were US$27,174 and US$23,343, respectively. Among osimertinib recipients, drug-related costs (including pharmacy and outpatient antineoplastic drug and administration costs) made up 61% (US$16,673) of total costs, inpatient costs 20% (US$5462), and other outpatient costs 16% (US$4432). In chemotherapy recipients, 59% (US$13,883) of total costs were drug-related, 5% (US$1166) were inpatient costs, and 33% (US$7734) other outpatient costs. CONCLUSIONS: Higher mean total cost of care was observed among patients receiving 1L TKI (osimertinib) than 1L chemotherapy in EGFRm advanced NSCLC. However, descriptive differences in type of spending and HRU were identified: higher inpatient costs and inpatient days for osimertinib versus higher outpatient costs for chemotherapy. Findings suggest that significant unmet needs may remain for 1L treatment of EGFRm NSCLC, and despite significant advances in targeted care, further individualized therapies are needed to balance benefits, risks, and total cost of care. Furthermore, observed descriptive differences in inpatient admissions may have implications for quality of care and patient quality of life, for which additional research is warranted.

Association Between Weight Gain and the Incidence of Cardiometabolic Conditions Among People Living with HIV-1 at High Risk of Weight Gain Initiated on Antiretroviral Therapy.

INTRODUCTION: Antiretroviral therapy (ART) has been associated with weight gain in people living with HIV-1 (PLWH); however, limited research has assessed whether early weight gain post-ART initiation is associated with metabolic or cardiovascular outcomes among PLWH at high risk of weight gain (i.e., female, Black or Hispanic). This study aimed to evaluate the incidence of metabolic and cardiovascular outcomes between PLWH at high risk of weight gain following an observed ≥ 5% or < 5% weight/body mass index (BMI) gain within 6 months following ART initiation. METHODS: A retrospective longitudinal study using Symphony Health, an ICON plc Company, IDV® electronic medical records (October 1, 2014-March 31, 2021) identified adult female, Black, or Hispanic treatment-naïve PLWH who initiated ART and who had ≥ 1 weight or BMI measurement pre- and within 6 months post-treatment (landmark period). Inverse probability of treatment weighting was used to account for differences between PLWH who experienced ≥ 5% and < 5% weight/BMI gain. The time to each outcome was compared between cohorts using weighted hazard ratios (HRs) after the landmark period. RESULTS: Weighted ≥ 5% and < 5% cohorts included 620 and 632 patients, respectively; baseline characteristics were similar between the two cohorts (mean age: ~ 48 years, ~ 59% female, ~ 49% Black, ~ 17% Hispanic). During a mean 2-year follow-up, PLWH with ≥ 5% weight/BMI gain were significantly more likely to be diagnosed with type 2 diabetes mellitus (T2DM; HR = 2.19; p = 0.044). There were no significant differences in the incidence of any other outcomes between the study cohorts. CONCLUSION: Despite a short 2-year follow-up, female, Black or Hispanic PLWH experiencing ≥ 5% weight/BMI increase within 6 months following ART initiation had an increased risk of T2DM, but not other metabolic or cardiovascular outcomes, likely due to the short follow-up period. Further research with longer follow-up and specific ART regimens is warranted to examine the impact of ART-related weight gain on long-term clinical outcomes.

Assessment of the Impact of a Meningitis/Encephalitis Panel on Hospital Length of Stay: A Systematic Review and Meta-Analysis.

Meningitis and encephalitis are central nervous system infections with considerable morbidity and mortality. The BioFire® FilmArray® Meningitis/Encephalitis Panel (multiplex ME panel) can identify pathogens rapidly potentially aiding in targeted therapy and curtail antimicrobial exposure. This systematic review and meta-analysis synthesized the literature on the association between the multiplex ME panel and length of hospital stay (LOS), length of acyclovir therapy, and days with antibiotics. MEDLINE and EMBASE were searched. Only studies presenting novel data were retained. Random-effects meta-analyses were performed to assess the impact of the multiplex ME panel on outcomes. Of 169 retrieved publications, 13 met the criteria for inclusion. Patients tested with the multiplex ME panel had a reduction in the average LOS (mean difference [MD] [95% CI]: -1.20 days [-1.96, -0.44], n = 11 studies). Use of the multiplex ME panel was also associated with a reduction in the length of acyclovir therapy (MD [95% CI]: -1.14 days [-1.78, -0.50], n = 7 studies) and a nonsignificant reduction in the average number of days with antibiotics (MD [95% CI]: -1.01 days [-2.39, 0.37], n = 6 studies). The rapidity of pathogen identification contributes to an overall reduced LOS, reductions in the duration of empiric antiviral utilization, and a nonsignificant reduction in antibiotic therapy.

Preventing rheumatoid arthritis: Preferences for and predicted uptake of preventive treatments among high risk individuals.

OBJECTIVE: To understand preferences for and estimate the likely uptake of preventive treatments currently being evaluated in randomized controlled trials with individuals at increased risk of developing rheumatoid arthritis (RA). METHODS: Focus groups were used to identify key attributes of potential preventive treatment for RA (reduction in risk of RA, how treatment is taken, chance of side effects, certainty in estimates, health care providers opinion). A web-based discrete choice experiment (DCE) was administered to people at-risk of developing RA, asking them to first choose their preferred of two hypothetical preventive RA treatments, and then between their preferred treatment and 'no treatment for now.' DCE data was analyzed using conditional logit regression to estimate the significance and relative importance of attributes in influencing preferences. RESULTS: Two-hundred and eighty-eight first-degree relatives (60% female; 66% aged 18-39 years) completed all tasks in the survey. Fourteen out of fifteen attribute levels significantly influenced preferences for treatments. How treatment is taken (oral vs. infusion ß0.983, p<0.001), increasing reduction in risk of RA (ß0.922, p<0.001), health care professional preference (ß0.900, p<0.001), and avoiding irreversible (ß0.839, p<0.001) or reversible serious side effects (ß0.799, p<0.001) were most influential. Predicted uptake was high for non-biologic drugs (e.g. 84% hydroxycholoroquine), but very low for atorvastatin (8%) and biologics (<6%). CONCLUSION: Decisions to take preventative treatments are complex, and uptake depends on how treatments can compromise on convenience, potential risks and benefits, and recommendations/preferences of health care professionals. This evidence contributes to understanding whether different preventative treatment strategies are likely to be acceptable to target populations.

Perspectives of patients, first-degree relatives and rheumatologists on preventive treatments for rheumatoid arthritis: a qualitative analysis.

BACKGROUND: There is growing evidence that it may be possible to identify people at high risk of developing rheumatoid arthritis (RA). Assuming that effective interventions were available, this could mean that treatments introduced in the pre-symptomatic phase could prevent or delay the onset of the disease. Our study aimed to identify the potential attributes involved in decision-making around whether or not to take preventive treatment for RA, in order to inform the development of a discrete choice experiment (DCE) to ascertain consumer preferences for a preventive treatment program for RA. METHODS: We conducted a focus group study to develop conceptual attributes, refine their meaning, and develop levels. Participants included RA patients, first-degree relatives of RA patients, and rheumatologists who were 18 years of age and over, could read and speak English, and could provide informed consent. Candidate attributes were refined through iterative rounds of data collection and analysis. All focus groups were audio-recorded and transcribed, and then analyzed using the Framework Method to identify, compare, and contrast key conceptual attributes. RESULTS: Attributes identified from analysis included: accuracy of the test, certainty in estimates, method of administration, risk of RA and risk of reduction with treatment, risk and seriousness of side effects, person recommending the test, and opinion of the health care professional. Patients with RA, first-degree relatives of patients, and rheumatologists all valued the accuracy of testing due to concerns about false positives, and valued certainty in estimates of the test and preventive treatment. Patients and first-degree relatives desired this evidence from a range of sources, including discussions with people with the disease and health care professionals, and their preferences were modified by the strength of recommendation from their health care professional. CONCLUSIONS: The role of the person who recommends a test and the opinion of a health care professional are novel potential attributes involved in decisions around whether or not to take preventive treatment for RA, that have not been included in previous DCEs.

Do patients and health care providers have discordant preferences about which aspects of treatments matter most? Evidence from a systematic review of discrete choice experiments.

OBJECTIVES: To review studies eliciting patient and healthcare provider preferences for healthcare interventions using discrete choice experiments (DCEs) to (1) review the methodology to evaluate similarities, differences, rigour of designs and whether comparisons are made at the aggregate level or account for individual heterogeneity; and (2) quantify the extent to which they demonstrate concordance of patient and healthcare provider preferences. METHODS: A systematic review searching Medline, EMBASE, Econlit, PsycINFO and Web of Science for DCEs using patient and healthcare providers. INCLUSION CRITERIA: peer-reviewed; complete empiric text in English from 1995 to 31July 2015; discussing a healthcare-related topic; DCE methodology; comparing patients and healthcare providers. DESIGN: Systematic review. RESULTS: We identified 38 papers exploring 16 interventions in 26 diseases/indications. Methods to analyse results, determine concordance between patient and physician values, and explore heterogeneity varied considerably between studies. The majority of studies we reviewed found more evidence of mixed concordance and discordance (n=28) or discordance of patient and healthcare provider preferences (n=12) than of concordant preferences (n=4). A synthesis of concordance suggested that healthcare providers rank structure and outcome attributes more highly than patients, while patients rank process attributes more highly than healthcare providers. CONCLUSIONS: Discordant patient and healthcare provider preferences for different attributes of healthcare interventions are common. Concordance varies according to whether attributes are processes, structures or outcomes, and therefore determining preference concordance should consider all aspects jointly and not a binary outcome. DCE studies provide excellent opportunities to assess value concordance between patients and providers, but assessment of concordance was limited by a lack of consistency in the approaches used and consideration of heterogeneity of preferences. Future DCEs assessing concordance should fully report the framing of the questions and investigate the heterogeneity of preferences within groups and how these compare.

A survey of gastrointestinal parasites of olive baboons (Papio anubis) in human settlement areas of Mole National Park, Ghana.

Fecal samples from 55 free-ranging olive baboons (Papio anubis) in Mole National Park, Ghana, were collected 22 June-7 July 2008 and analyzed for gastrointestinal parasites. This is the first survey of baboon gastrointestinal parasites in Ghana and provides baseline data for this area. Ninety-three percent of samples were infected, leaving 7% with no parasites observed. Of those infected, there was a 76% prevalence of strongyles, 53% Strongyloides spp., 11% Abbreviata caucasica , 62% prevalence of Balantidium coli (trophozoites and cysts identified), 4% Entomeba hystolytica/dispar, and 47% unidentified protozoan parasites. Of the strongyle infections, 9% were identified as Oesophagostamum sp. One sample contained an unidentified spirurid nematode that resembled Gongylonema sp. Mole has a mixed forest-savanna habitat, and baboons frequently range into human areas, which makes them subject to parasites from each habitat and multiple sources of exposure. We found a high prevalence of nematode parasites, consistent with a wet or cooler forest environment, or high rates of fecal contamination. The presence of Strongyloides sp., E. hystolitica/dispar, and B. coli suggest potential public health risk from baboons, but molecular identification of these parasites, and documentation of their presence in local human populations, would be necessary to confirm zoonotic transmission.