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Supplements Improving Clinical and Managed Care Outcomes in Rheumatoid arthritis: a Focus on Comparative Effecti

Implications for Managed Care and Specialty Pharmacy in Rheumatoid Arthritis

William J. Cardarelli, PharmD
A recent meta-analysis examined the impact of early treatment on radiographic progression in RA.24 Compared with early treatment initiation, delayed treatment initiation was associated with a –0.19 standardized mean difference (95% CI, –0.34 to –0.04), which corresponded to a 33% reduction (95% CI, –50% to –16%) in long-term progression (Figure 1). Patients with more aggressive disease demonstrated a greater benefit from DMARD initiation (P = .04).24 A recent analysis compared the cost-effectiveness of 6 DMARD-based approaches to early treatment, including monotherapy, step-up combination, parallel combination, intensive step-up combination, step-down combination, and a steroid plus monotherapy (Table).25 Step-down combination therapy exceeded monotherapy, step-up, parallel, and steroid combinations, because it was less costly and more effective, and thus dominated the other strategies with the exception of the intensive strategy. Comparing the remaining strategy (intensive DMARD combination) to step-down treatment, the estimated incremental cost-effectiveness ratio (ICER) was £27,392. The authors assumed that decision makers adopt a threshold of £20,000 (approximately US$29,000) per QALY, thus the value of each strategy can be expressed in monetary terms; using QALY to determine a net benefit, the best strategy would be that with the greatest net benefit. In this case, step-down combination therapy (£258k) had the greatest net benefit and could be considered the most cost-effective.25

Another study compared sequential monotherapy, stepup combination, monotherapy with prednisone, and combination therapy with infliximab.26 Figure 2 demonstrates the 2-year costs in 2008 euros (1 euro equals approximately US$1.25) of these regimens using 3 different pharmacoeconomic models. The models show that infliximab had a larger increase in QALYs, but that cost-effectiveness was only improved with work productivity in the human capital method. The friction method only accounts for productivity losses up to 6 months, and assumes an employee is replaced or back to work at that point. The human capital method accounts for sustained productivity. Thus, depending on the model, high-cost items could be cost-effective as long as cost utility is improved and work productivity is associated with an improvement in QALYs.26 Thus, it appears that aggressive treatment of early RA, compared with monotherapy regimens, is cost-effective using step-down combination therapy or combination with a TNF inhibitor due to enhanced efficacy, improvements in QALY, and improved productivity. These results confirm other published findings. 27-29 The lowest direct cost would be from DMARD optimization,27-29 but biologics as monotherapy are also considered cost-effective, with ICERs ranging from $50,000 to $100,000 (Figure 3).28 Consequently, biologics in combination with DMARDs for early RA have mostly proved not to be-cost-effective, due to ICERs greater than $100,000 in 6 of 7 (85.7%) studies.28 Figure 3 also demonstrates that when initial therapy fails, biologics after DMARD failure had ICERs less than $100,000 in 14 of 18 studies (77.8%), and biologics after TNF inhibitor failure had ICERs less than $100,000 in 4 out of 4 studies (100%).28 A separate systematic review of biologics for DMARD failure evaluated several scenarios using 2009 Canadian dollars ($1 Canadian equals approximately US$1.01).30 When methotrexate monotherapy failed, methotrexate monotherapy was compared with biologic combination with methotrexate, and all 20 comparisons found ICER values ranging from $6000 to $92,000, suggesting cost-effectiveness at a willingness to pay threshold of $100,000 per QALY. Seven of 12 (58.3%) of these comparisons conducted from a societal perspective and 2 of 8 (25%) from a payer perspective found the therapy cost-effective at a willingness to pay threshold of $50,000 per QALY. When patients who failed to respond to methotrexate combination therapy or sequential DMARD administration were compared with those who received additional DMARD sequencing or a biologic alone or in combination with a DMARD, 14 of 35 (40%) comparisons had ICERs below the $100,000 threshold. Median ICERs per QALY were $81,000 (range, $63,000-$383,000) for adalimumab, $79,000 (range, $60,000-$175,000) for adalimumab plus methotrexate, $127,000 (range, $45,000-$612,000) for etanercept, $75,000 (range, $72,000-$134,000) for etanercept plus methotrexate, and $133,000 (range, $80,000-$378,000) for infliximab plus methotrexate.30 When biologics were evaluated after TNF inhibitor failure in 4 studies, rituximab and abatacept had ICER values less than $50,000 per QALY, and abatacept and etanercept had ICER values less than $100,000 in 2 of the studies (Figure 3). Thus, biologic agents have the potential to be cost-effective, especially when used in combination with DMARDs for DMARD failure, and are cost-effective for TNF inhibitor failure, particularly when rituximab or abatacept are used.28

Role of Managed Care and Specialty Pharmacy

Given the data on efficacy of pharmaceuticals in RA, managed care organizations have been left with a difficult decision regarding the most effective allocation of agents for optimal disease management. Historically, specialty items like the biologics were covered under the medical benefit. Under the medical benefit, where agents were primarily given in the physician’s office, it was difficult to track agent selection and sequence, as it was done for adjudicated claims through a pharmacy benefit management (PBM) company.31 However, costs for specialty drugs have been increasing while those for traditional medications remain static, and the market for RA medications is expected to increase.32,33 In an effort to control selection and sequence of agents, PBM companies acquired or contracted with specialty pharmacies to manage administration of high-cost medications. By managing these medications as part of the pharmacy benefit, specialty pharmacies ensure safe handling, restrict drug distribution, and can contract with pharmaceutical companies to get better acquisition rates and pass the savings along to the payers and patients compared with physician offices and clinics.31 An important factor in treatment adherence, and hence efficacy of an agent, is the amount of cost-sharing a patient has to bear. A recent study indicated that for patients with RA or multiple sclerosis (MS), out-of-pocket (OOP) expenses of more than $100 for TNF inhibitors (RA OOP $0-$100, 4.7% abandonment; RA OOP >$100, 10.5%- 26.4% abandonment; P <.001), or $200 for MS medications (MS OOP $0-$200, 5.3%-10.6% abandonment; RA OOP >$200, 25.8%-28.5%; P <.001 compared with $0-$100) were associated with increased risk of prescription abandonment.34 A systematic review identified that the 2 most important factors in adherence to RA treatment were the relationship between the patient and the provider, and the belief that the medication was necessary.35 In another study, factors important in filling the initial DMARD prescription included communication with, and trust in, the rheumatologist, and perceptions about the medication, such as perceived adverse effects. Factors associated with subsequent adherence included experience with the medication (eg, development of adverse effects), ability to fit the medication schedule into daily life, and level of engagement in decision making.36 The final factor determining adherence appears to be the medication itself. One recent study identified differences in adherence and discontinuation between anakinra, infliximab, and etanercept.37 The proportion of days covered (goal ≥0.8) was 0.36 for anakinra, 0.57 for etanercept, and 0.64 for infliximab, with respective adherence rates of 11%, 32%, and 43%, and discontinuation rates of 76%, 41%, and 41%.37 These data highlight the importance of the relationship between a patient and their provider, the need for education, and the importance of agent selection in ensuring that the benefit of RA therapy is optimized.

Specialty pharmacies manage utilization, monitor patients, and ensure adherence to reduce the potential for adverse effects or suboptimal treatment. Specialty pharmacies are able to provide these services by obtaining prior authorization for patients, ensuring step-up therapy by documenting patients who have not responded to prior therapy before receiving approval for more expensive agents, providing patient and provider training, determining quantity limits so that reauthorization is needed, determining dosing limits, establishing length of therapy limits, selecting alternative agents, and providing case management services.31 The next section highlights some disease management programs in RA that have successfully improved patient outcomes.

Optimizing Clinical and Economic Outcomes With Disease Therapy Management

A focus group study completed recently in Quebec, Canada, sought to evaluate barriers to optimal care of patients with RA.38 Barriers were divided into 4 categories: prior to primary care contact, speed of referral to a specialist, barriers to treatment, and inadequate resources. In the initial stage, there was a lack of awareness in the general population about RA, and patient demographics (eg, sex, age, socioeconomic status) can affect access to care. Once a patient is seen, primary care physicians may not differentiate the symptoms of RA from other inflammatory processes, and delay referral to a specialist. Patient demographic factors may also affect referral to a specialist. There are also access issues, which are barriers to being seen by rheumatologists. Results demonstrated that during treatment, primary care physicians are not comfortable initiating definitive therapy, communication between physicians and patients is lacking, and the role of the primary care physician in optimizing care is uncertain. The focus group also identified that interdisciplinary care could improve outcomes, but is often lacking, and that patient education is inadequate. In regard to the need for adequate resources, the main need was for a team approach across multiple disciplines.38 Thus, special attention to patients with RA and a multidisciplinary approach may be useful in improving outcomes.

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