Role of phototherapy in the era of biologics.

Phototherapy is a safe and effective treatment for many dermatologic conditions. With the advent of novel biologics and small molecule inhibitors, it is important to critically evaluate the role of phototherapy in dermatology. Surveys have shown that many dermatology residency programs do not dedicate time to teaching residents how to prescribe or administer phototherapy. Limitations of phototherapy include access to a center, time required for treatments, and insurance approval. Home phototherapy, a viable option, is also underused. However, it should be emphasized that modern phototherapy has been in use for over 40 years, has an excellent safety profile, and does not require laboratory monitoring. It can be safely combined with many other treatment modalities, including biologics and small molecule inhibitors. In addition, phototherapy costs significantly less than these novel agents. Dermatologists are the only group of physicians who have the expertise and proper training to deliver this treatment modality to our patients. Therefore, to continue to deliver high-quality, cost-effective care, it is imperative that phototherapy be maintained as an integral part of the dermatology treatment armamentarium.

Biological Retention Rates, the Reasons of Switching, and Prognostic Factors in Patients with Psoriasis Treated Biologics.

OBJECTIVE: To review patients who were treated at Tokai University Hospital with biologic agents for psoriasis vulgaris and psoriatic arthritis and analyze the biological retention rate, reasons for switching biologics, and investigate possible clinical prognostic factor which may affect whether a patient preferred one biologic to another. METHODS: Clinical courses of 63 patients who received biologic agents between Sep of 2010 to June of 2019 were investigated. Biological retention rate of each biologic agents, reasons of switching to another biologic agent, and prognostic factors, if any, between switched and non-switched patients were examined. RESULTS: The biological retention rate of ustekinumab (UST) was significantly longer than that of infliximab (IFX) or adalimumab (ADA). The major reason of switching was due to secondary loss of efficacy. Patients being treated with UST were more likely to switch to another biologic when they exhibited nail lesions. CONCLUSION: These results suggested that biological retention rate of UST was superior than that of IFX or ADA. Furthermore, with patients administered UST, nail symptom suggested possible clinical prognostic factor for switching to other biologic agents.

Personalized rheumatic medicine through dose reduction reduces the cost of biological treatment - a retrospective intervention analysis.

Objective: The effects of a dose-reduction intervention of biological disease-modifying anti-rheumatic drugs (bDMARDs) in patients in remission were analysed with epidemiology and health economics strategies. The aims were to analyse changes in bDMARD dosage, evaluate potential disease worsening, and estimate cost reduction. Method: This uncontrolled single-centre observational study analysed bDMARD-treated patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and spondyloarthritis (SpA). bDMARD expenditure constituted a proxy for bDMARD doses, which enabled group-level analysis. Interrupted time-series regression was used to analyse changes in treatment cost due to the dose reduction. Disease activity and treatment durations were monitored to investigate disease worsening. Results: In total, 997 biological treatment cases were analysed. This involved 527 bDMARD patients, where an unknown fraction of patients was given reduced doses. Disease activity of RA and PsA patients decreased from 2001 to 2009 and remained stable after that, while disease activity for SpA patients was unchanged, indicating no disease worsening from the intervention. The dose tapering resulted in decreased bDMARD expenditure, indicating a decrease in bDMARD consumption, which led to an accumulated cost reduction of 4 178 000 EUR. Conclusions: The results suggest that dose reduction can be safely performed in patients in treatment remission on a group level without compromising treatment efficacy. Subcutaneous bDMARDs, including abatacept, adalimumab, and etanercept, were observed to be well suited to customizing dosage. This study highlights the potential for individualized and personalized rheumatic medicine by providing dose reduction to individual patients, while monitoring disease activity.

Cost-effectiveness of abatacept, tocilizumab and TNF-inhibitors compared with rituximab as second-line biologic drug in rheumatoid arthritis.

OBJECTIVES: The objective of this study was to evaluate the cost-effectiveness of abatacept, tocilizumab, and tumor necrosis factor (TNF) inhibitors as compared with rituximab in Finnish rheumatoid arthritis patients, who have previously been treated with TNF inhibitors. METHODS: A patient-level simulation model was developed to predict costs and outcomes associated with four biological drugs (abatacept, tocilizumab, rituximab and TNF inhibitors) in the treatment of rheumatoid arthritis. Following lack of efficacy or adverse events, the patients were switched to another biological drug until all four options were exhausted. After that, the patients were assumed to receive a 6th line treatment until death. The patients' baseline characteristics and regression models used in the simulation were based on observational data from the National Register for Biological Treatments in Finland. Direct costs comprised drug costs, administration costs, costs of switching, and outpatient and inpatient care, while indirect costs included disability pension and sick leaves due to rheumatoid arthritis. Several subgroup and deterministic sensitivity analyses were conducted. RESULTS: Drug costs were the lowest for rituximab, but when administration costs and costs of switching were included, drug costs were the lowest for TNF inhibitors. Abatacept was associated with the highest drug costs, whereas rituximab was associated with the highest healthcare costs. In total, TNF inhibitors had the lowest direct costs, while rituximab had the highest direct costs. The amount of quality-adjusted life years (QALY) gained ranged from 9.405 for rituximab to 9.661 for TNF inhibitors. TNF inhibitors, abatacept, and tocilizumab were dominant in comparison to RTX. CONCLUSIONS: TNF inhibitors, abatacept, and tocilizumab had lower costs and higher QALYs than rituximab, and therefore, they were dominant in comparison to rituximab. As TNF inhibitors had the lowest costs and highest QALYs, they were the most cost-effective treatment option.

Tapering biologic therapy for people with rheumatoid arthritis in remission: A review of patient perspectives and associated clinical evidence.

OBJECTIVES: Biologic therapies have increased the control of disease activity in rheumatoid arthritis (RA). Questions remain about tapering biologics when remission is achieved in RA. The patient perspective has to be incorporated in pragmatic applications of tapering but is rarely accounted for in clinical studies of tapering. The aim of the present review was to summarize the evidence about RA patient perspectives on biologic tapering. METHODS: We provided a narrative summary of the currently small body of research on patient perspectives retrieved through systematic searches with an emphasis on seeking qualitative research. In addition, we provided an update on relevant clinical research and financial considerations that frame the findings on patient perspectives. RESULTS: Financial considerations around commencing/continuing on biologic therapies in RA vary internationally and have implications for patient perspectives. Recent clinical studies indicate that the benefit of tapering biologic therapy when in remission are predicted by drug concentration and aspects of disease activity, severity and duration. Three major concerns have been identified from studies of patient perspectives on biologic tapering: (a) disease relapse; (b) access to treatment in the case of disease flare when tapering; and (c) local motivation for dose reduction (i.e., driven by funding or health benefit). CONCLUSIONS: More research is needed on tapering biologics, and should include studies of patient perspectives as well as health economic evaluations. Patient decision aids are a potential way of applying clinical and patient-focused evidence to help all parties come to a decision, but require developmental research and pragmatic evaluation.

Concordance Rate between Clinicians and Watson for Oncology among Patients with Advanced Gastric Cancer: Early, Real-World Experience in Korea.

Backgrounds/Aims: Watson for Oncology (WFO) is a cognitive technology that processes medical information by analyzing the latest evidence and guidelines. However, studies of the concordance rate between WFO and clinicians for advanced gastric cancer (AGC) are lacking. Methods: We retrospectively reviewed 65 patients with AGC who consulted WFO and the Gachon Gil Medical Center multidisciplinary team (GMDT) in 2016 and 2017. The recommendations of WFO were compared with the opinions of the GMDT. WFO provided three treatment options: recommended (first treatment option), for consideration (second treatment option), and not recommended. Results: In total, 65 patients (mean age 61.0 years; 44 males and 21 females) were included in the study. The concordance rate between WFO and the GMDT was 41.5% (27/65) at the recommended level and 87.7% (57/65) at the for consideration level. The main causes of discordance between WFO and the GMDT were as follows. First, WFO did not consider the medical history. Second, WFO recommended the use of agents that are considered outdated in Korea. Third, some patients wanted to be involved in a clinical trial. Fourth, some patients refused to use the biologic agents recommended by WFO for financial reasons as they were not covered by medical insurance. Conclusions: The concordance rate at the recommended level was relatively low but was higher at the for consideration level. Discordances arose mainly from the different medical circumstances at the Gachon Gil Medical Center (GMC) and the Memorial Sloan Kettering Cancer Center (MSKCC), the main WFO consulting center. The utility of WFO as a tool for supporting clinical decision making could be further improved by incorporating regional guidelines.

Cost evolution of biological agents for the treatment of spondyloarthritis in a tertiary hospital: influential factors in price.

Background Spending on biological agents has risen dramatically due to the high cost of the drugs and the increased prevalence of spondyloarthritis. Objective To evaluate the annual cost per patient and cost for each biological drug for treating patients with spondyloarthritis from 2009 to 2016, and to calculate factors that affect treatment cost, such as optimizing therapies by monitoring drug serum levels, the use of biosimilar-TNF inhibitors, and official discounts or negotiated rebates in biologicals acquired by the pharmacy department. Method Retrospective, observational study in a Spanish tertiary hospital. Main outcome Annual cost per patient and per drug. Factors that influenced the costs and socio-demographic parameters and disease activity. Results A total of 129, 215, and 224 patients were treated in 2009, 2013, and 2016, respectively. The annual cost per patient decreased: EUR11,604 in 2009, EUR8513 in 2013, and EUR7464 in 2016. The introduction of new drugs drives economic competition, leading to total savings per drug, with discounts reaching 5.8, 12.4, 16.7, 17.7, 13.7, and 24.8% for original infliximab, etanercept, adalimumab, ertolizumab, golimumab, and secukinumab, respectively, while rebates for biosimilar infliximab reached 31.90% in 2016. The number of patients with optimized therapies reached 47.5% in 2016, which led to cost savings of EUR798,614, in addition to savings from official discounts and rebates of EUR252,706 and savings from optimized therapies of EUR545,908 in 2016. Conclusion The cost of biological treatments declined after official discounts, negotiated rebates, and optimized therapies, leading to a significant decrease in the annual cost per patient. The greatest contribution to economic savings in biological therapy according to our study was biological therapy optimization.

Cost-effectiveness analysis of sequential biologic therapy with ixekizumab versus secukinumab as first-line treatment of moderate-to-severe psoriasis in the UK.

AIMS: Patients with psoriasis often undergo treatment with a sequence of biologic agents because of poor/loss of response to initial therapy. With the availability of newer agents like ixekizumab and secukinumab, there is a need for cost-effectiveness analyses to better reflect current clinical practice. This study aimed to assess the cost-effectiveness of a sequence of biologic therapies containing first-line ixekizumab vs first-line secukinumab in patients with moderate-to-severe plaque psoriasis in the UK. MATERIALS AND METHODS: A Markov model with a lifetime horizon was developed to compare the cost-effectiveness of ixekizumab and secukinumab treatment sequences: ixekizumab → ustekinumab → infliximab → best supportive care (BSC) vs secukinumab → ustekinumab → infliximab → BSC. The model used monthly cycles, and included four health states: trial period, treatment maintenance, BSC, and death. At the end of the trial period, responders transitioned to maintenance therapy; non-responders transitioned to the next biologic in the sequence. An annual discontinuation rate of 20% was assumed for maintenance therapy. RESULTS: The ixekizumab sequence provided cost savings of £898 (£176,203 vs 177,101) [year 2015 values] and gained 0.03 more quality-adjusted life-years (QALYs: 1.45 vs 1.42) vs the secukinumab sequence over the lifetime horizon. Probabilistic sensitivity analysis showed an 89.8% likelihood that the ixekizumab sequence would be cost-effective at a threshold of £20,000 per QALY gained. LIMITATIONS: The analysis used list prices for drugs rather than confidential, preferentially priced Patient Access Scheme costs. In addition, efficacy input data were based on a network meta-analysis, as there were no head-to-head trials comparing ixekizumab and secukinumab. CONCLUSION: First-line treatment with ixekizumab as part of a specific sequential biologic therapy for moderate-to-severe plaque psoriasis in the UK provided slight advantages in cost savings and QALYs gained over a similar treatment sequence initiated with secukinumab. In view of the small magnitude of these differences, factors such as patient preferences (e.g. for number of injections) and long-term safety (e.g. related to time on the market) may also be important for clinical decision-making.

Availability and affordability of biologic versus non-biologic anticancer medicines: a cross-sectional study in Punjab, Pakistan.

OBJECTIVES: Prime focus of this study was to evaluate the availability and affordability of originator brands (OBs) and lowest price generics (LPGs) of prescribed biologic and non-biologic anticancer medicines. DESIGN, SETTINGS AND PARTICIPANTS: A descriptive, cross-sectional survey was conducted in 22 cancer-care hospitals (18 public hospitals and 4 private hospitals) and 44 private pharmacies in Punjab, Pakistan. Sampling population consisted of 4483 patients with cancer aged ≥18 years. The availability was determined by classifying anticancer medicines in four categories: absent/unavailability (medicines not present in any surveyed facility), low availability (medicines present in <50% of surveyed facilities), fairly high availability (medicines present in 50%-74% of surveyed facilities) and high availability (medicines present in >75% of surveyed facilities). Medicines were affordable if overall cost of all the prescribed anticancer medicines were 20% of the household capacity to pay. Data were analysed by using Statistical Packages for Social Sciences (IBM SPSS Statistics for Windows, V.21.0). RESULTS: A total of 5060 patients with cancer were approached out of which 4483 patients were included in the survey. Overall, 10 103 anticancer drugs were prescribed. Among them, 96.3% were non-biologics and 3.7% were biologics. Oncologists were reluctant to prescribe biologics due to high prices. 58.1% of non-biologics were affordable; whereas, the affordability of biologics was 3.3%. A total of 43.9% of both biologic and non-biologic OBs were available; whereas, their affordability was 44.2%. On the other hand, the availability of LPGs was 21.3%, and their affordability was 66.1%. For low-income patients, the affordability of non-biologics was 31.6% and the affordability of biologics was 1.1%. CONCLUSIONS: Most of the patients with cancer were prescribed non-biologics due to their low price and better affordability. In contrast to OBs, LPGs of both biologics and non-biologics had less availability but more affordability.

Direct medical costs and their predictors in the EMAR-II cohort: "Variability in the management of rheumatoid arthritis and spondyloarthritis in Spain". / Costes médicos directos y sus predictores en la cohorte "Variabilidad en el manejo de la artritis reumatoide y las espondiloartritis en España".

OBJECTIVE: To analyze the resource utilization in rheumatoid arthritis (RA) patients and predictive factors in and patients treated with biological drugs and biologic-naïve. METHODS: A cross-sectional study was performed in a sample including all regions and hospitals throughout the country. Sociodemographic data, disease activity parameters and treatment data were obtained. Resource utilization for two years of study was recorded and we made costs imputation. Correlation analyzes were performed on all RA patients and those treated with biological and biological naïve, to estimate the differences in resource utilization. Factors associated with increased resources utilization (costs) attending to treatment was analyzed by linear regression models. RESULTS: We included 1,095 RA patients, 26% male, mean age of 62±14 years. Mean of direct medical costs per patient was €24,291±€45,382. Excluding biological drugs, the average cost per patient was €3,742±€3,711. After adjustment, factors associated with direct medical costs for all RA patients were biologic drugs (P=.02) and disease activity (P=.004). In the biologic-naïve group, the predictor of direct medical costs was comorbidity (P<.001). In the biologic treatment group predictors were follow-up length of the disease (P=.04), age (P=.02) and disease activity (P=.007). CONCLUSION: Our data show a remarkable economic impact of RA. It is important to identify and estimate the economic impact of the disease, compare data from other geographic samples and to develop improvement strategies to reduce these costs and increase the quality of care.

Estimating preferences for modes of drug administration: The case of US healthcare professionals.

BACKGROUND: There are hidden drug administration costs that arise from a mismatch between end-user preferences and how manufacturers choose to formulate their drug products for delivery to patients. The corollary of this is: there are "intangible benefits" from considering end-user preferences in manufacturing patient-friendly medicines. It is important then to have some idea of what pharmaceutical manufacturers should consider in making patient-friendly medicines and of the magnitude of the indirect benefits from doing so. OBJECTIVES: This study aimed to evaluate preferences of healthcare professionals in the US for the non-monetary attributes of different modes of drug administration. It uses these preference orderings to compute a monetary valuation of the indirect benefits from making patient-friendly medicines. METHODS: A survey collected choice preferences of a sample of 210 healthcare professionals in the US for two unlabelled drug options. These drugs were identical except in the levels of attributes of drug administration. Using the choice data collected, statistical models were estimated to compute gross welfare benefits, measured by the expected compensating variation, from making drugs in a more patient-friendly manner. RESULTS: The monetary value of end-user benefits from developing patient-friendly drug delivery systems is: (1) as large as the annual acquisition costs per full treatment episode for some biologic drugs; and (2) likely to fall in the "high end" of the distribution of the direct monetary costs of drug administration. CONCLUSIONS: An examination of end-user preferences should help manufacturers make more effective and efficient use of limited resources for innovations in drug delivery system, or manufacturing research in general.

Comparing biologic persistence and healthcare costs in rheumatoid arthritis patients initiating subcutaneous biologics.

AIM: Comparing biologic persistence and healthcare costs between rheumatoid arthritis (RA) patients initiating first- or second-line subcutaneous abatacept, adalimumab, or etanercept. MATERIALS & METHODS: Retrospective, observational cohort study, which included adults with RA who initiated either of the three treatments between 29 July 2011 and 1 July 2015. Total healthcare costs were measured during baseline and follow-up. Biologic persistence was compared using multivariable Cox proportional hazards regression. RESULTS: Subcutaneous abatacept-treated patients had numerically lowest adjusted hazards of nonpersistence and increase from baseline in total healthcare costs. Sensitivity analyses measuring outcomes over an alternative follow-up definition produced consistent results. CONCLUSION: Abatacept-treated RA patients appeared to have the poorest health status yet often had the lowest increase from baseline in healthcare costs and longest duration of biologic persistence.

Triple Therapy Versus Biologic Therapy for Active Rheumatoid Arthritis: A Cost-Effectiveness Analysis.

Background: The RACAT (Rheumatoid Arthritis Comparison of Active Therapies) trial found triple therapy to be noninferior to etanercept-methotrexate in patients with active rheumatoid arthritis (RA). Objective: To determine the cost-effectiveness of etanercept-methotrexate versus triple therapy as a first-line strategy. Design: A within-trial analysis based on the 353 participants in the RACAT trial and a lifetime analysis that extrapolated costs and outcomes by using a decision analytic cohort model. Data Sources: The RACAT trial and sources from the literature. Target Population: Patients with active RA despite at least 12 weeks of methotrexate therapy. Time Horizon: 24 weeks and lifetime. Perspective: Societal and Medicare. Intervention: Etanercept-methotrexate first versus triple therapy first. Outcome Measures: Incremental costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). Results of Base-Case Analysis: The within-trial analysis found that etanercept-methotrexate as first-line therapy provided marginally more QALYs but accumulated substantially higher drug costs. Differences in other costs between strategies were negligible. The ICERs for first-line etanercept-methotrexate and triple therapy were $2.7 million per QALY and $0.98 million per QALY over 24 and 48 weeks, respectively. The lifetime analysis suggested that first-line etanercept-methotrexate would result in 0.15 additional lifetime QALY, but this gain would cost an incremental $77 290, leading to an ICER of $521 520 per QALY per patient. Results of Sensitivity Analysis: Considering a long-term perspective, an initial strategy of etanercept-methotrexate and biologics with similar cost and efficacy is unlikely to be cost-effective compared with using triple therapy first, even under optimistic assumptions. Limitation: Data on the long-term benefit of triple therapy are uncertain. Conclusion: Initiating biologic therapy without trying triple therapy first increases costs while providing minimal incremental benefit. Primary Funding Source: The Cooperative Studies Program, Department of Veterans Affairs Office of Research and Development, Canadian Institutes for Health Research, and an interagency agreement with the National Institutes of Health-American Recovery and Reinvestment Act.

Is there potential for therapeutic drug monitoring of biologic agents in rheumatoid arthritis?

The use of biologics has significantly changed the management of rheumatoid arthritis over the last decade, becoming the cornerstone treatment for many patients. The current therapeutic arsenal consists of just under 10 biologic agents, with four different mechanisms of action. Several studies have demonstrated a large interindividual pharmacokinetic variability, which translates to unpredictability in clinical response among individuals. The present review focuses on the pharmacokinetics and pharmacodynamics of biologic agents approved for rheumatoid arthritis. The literature relating to their concentration-effect relationship and the use of pharmacokinetic-pharmacodynamic modelling to optimize drug regimens is analysed. Due to the scarcity and complexity of these studies, the current dosing strategy is based on clinical indexes/aspects. In general, dose individualization for biologics should be implemented increasingly in clinical practice as there is a direct benefit for treated rheumatoid arthritis patients. Moreover, there is an indirect benefit in terms of cost-effectiveness.