Managed Care Implications in Managing Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a systemic inflammatory form of arthritis characterized by joint inflammation, pain, swelling, and stiffness. While contemporary treatment strategies based on early diagnosis, aggressive treatment, and regular monitoring have helped a significant number of patients achieve evidence-based treatment goals, RA still presents substantial management challenges to both clinicians and patients, and has the potential to lead to severe disability over time. In addition to its significant clinical consequences, RA has important economic implications. Both direct and indirect medical costs associated with RA are significant, including costs of medications, ambulatory and office-based care, and quality-of-life and productivity costs. In addition, a significant proportion of patients with prevalent RA have associated cardiovascular disease and other comorbidities, further compounding healthcare costs and complicating management of this disorder. Clinically favorable and cost-effective management must focus on prevention of disease progression and the improved patient health status and productivity than can result from optimal disease control. With the myriad of treatment options both available and emerging, managed care organizations are faced with difficult decisions surrounding the most clinically and cost-effective allocation of treatments designed to improve disease outcomes for patients with RA. It is vital that managed care clinicians and providers analyze both the overall burden and the specific costs of RA. This will allow a better understanding of how costs and issues relating to healthcare utilization affect the treatment of patients with RA and impact individualized therapy, care coordination, and outcomes.

(Am J Manag Care. 2014;20:S145-S152) http://www.ajmc.com/_media/_upload_image/ACE017_May14_RA-CE_Owens_Figure.pngThe Economic Impact of RA

While the clinical burden of rheumatoid arthritis (RA) is significant in and of itself, the patient and societal costs associated with this disorder are also substantial.¹ Breaking down these outlays using cost-of-illness principles, a spectrum including direct, indirect, and intangible costs, can substantially impact management of RA. Direct costs associated with RA consist of the expenditures directly attributed to healthcare utilization. These expenditures include those for clinical consultation (primary and specialty care), biologic and imaging assessments, outpatient/office-based care, and inpatient care, which includes admissions for disease-related symptoms and/or surgery (such as joint replacement). Other direct costs include those incurred by emergency department visits, physical therapy, pharmaceutical treatments and related expenditures, and medical costs beyond the treatment of joint disease itself.^1-3 The costs of such care may also include those related to nonmedical costs, such as out-of-pocket expenses incurred for caregivers or care that is not reimbursed on a regular basis.² Indirect costs usually refer to loss of productivity, including paid productivity loss associated with employment, and loss of productivity outside the workplace, such as in the community or the home. These indirect costs may be classified in terms of productivity losses borne by the patient, the patient’s family, and the patient’s employer, as well societal costs (morbidity), and costs of lost productivity due to premature death caused by RA-related illness (mortality). Finally, intangible costs should also be considered, relating to the cost of patient suffering from pain or disability associated with RA along with diminished self-esteem and well-being. While such costs may be substantial in addition to the oftenmeasured direct and indirect costs, they are, unfortunately, rarely quantified, and lack the hard data needed for their actual burden to be assessed.^2,4

An early major systematic review, published in 2000 and utilizing 4 computerized literature databases, was performed to assess costs associated with RA, as analyzed by 14 costof- illness studies.⁴ Costs were reported in 1996 dollars based upon the consumer price index for medical care. The actual costs calculated in the different studies included in the review varied across all cost categories. Overall, the analysis revealed that mean annual direct costs associated with RA averaged $5720 per patient per year. Mean costs for outpatient visits and inpatient hospital stays were $1855 and $4944, respectively. Indirect costs usually referred to the number of days absent from work annually, and these ranged from 2.7 to 30 days per year per employed patient. The mean annual indirect cost associated with RA was found to be $5822. The authors noted that by calculating mean cost as the main statistic published to date at that time, it was likely that the study overestimated the annual per-person costs of RA owing to a positively skewed distribution attributed to cost data. It is important to note that, for this analysis, inpatient costs were found to be the largest total annual medical costs associated with RA at that time, accounting for between 17% and 88% of total medical costs. Medication constituted between 8% and 24% of total costs, and physician visits accounted for 8% to 21% of total costs. It must be noted that this study was performed in 2000 and provides a historical perspective of the breakdown of costs associated with RA at that time, which may be compared with more current assessments.

Additional analyses of RA-associated costs have produced very wide ranges of cost estimations. A study published in 2004 estimated that direct medical costs ranged from $2298 to $13,549 per patient.5,6 More recent data have resulted in estimates of annual per patient direct medical costs of RA ranging from $2000 to $10,000, with estimates for indirect costs ranging from $1500 to $22,000.^1,7,8 A large number of cost-of-illness studies have been performed in recent decades, and significant variability among these studies has been found. The main sources of discrepancies between the studies include sample characteristics (study size, RA characteristics such as severity and duration), the healthcare organization involved, and the methodology used to perform the cost calculations. While cost estimations have varied, it is well understood that the economic burden of RA has evolved significantly over the past decade, driven primarily by the launch of biologic therapies for treatment of the disorder and costs associated with the use of these medications rather than the higher inpatient costs identified as the primary cost driver in RA at the beginning of the century.^2,4

Specialty Medication Costs

The US Food and Drug Administration does not designate individual medications or classes of drugs as specialty related; instead, this designation is frequently defined internally by a health plan or pharmacy benefit management service. These designations can vary substantially among different health plans and organizations, but are usually associated with a cost cutoff.⁹ Specialty drugs are often designated as such by the condition they are designed to treat, and these agents have provided new therapeutic options for many chronic conditions.

Such pharmaceuticals have demonstrated great efficacy and promise; however, this effectiveness does not come without cost. Historically, these medications were developed to treat only rare conditions that affected a limited number of patients, and were considered a good value despite their expense because they made treatment possible for patients with difficult-to-treat disorders who otherwise had limited therapeutic options.¹⁰ In recent years specialty drugs have become the designated standard of care for many common chronic diseases, including RA.^9,10 The use of these agents has increased more rapidly than the use of traditional therapies and, because of this, payers are more carefully scrutinizing their associated costs and evidence for their actual value in patient management.9

In 2011 it was estimated that spending on specialty drugs accounted for approximately 25% of the total prescription drug spending processed via the medical and pharmacy benefit.⁹ These specialty agents are expected to account for 50% of the total spending for prescription drugs by 2018.^9,11 As this type of spending continues to grow at a rate faster than that associated with more traditional treatments, payers and policy makers must better comprehend the costs of these drugs along with their clinical benefits so they are better able to implement appropriate therapy decision making for patients with the chronic disorders these agents are designed to treat.⁹ The treatment landscape is complicated by the fact that comparatively little is known about the actual utilization of specialty drugs and related spending in diseases such as RA, for which use of such agents is frequent, especially when assessed in relation to an individual patient’s total healthcare costs. It is challenging to accurately assess the use of specialty drugs and member spending across pharmacy and medical benefit databases due to limited access to these data and differences in how specialty drugs are captured in medical and pharmacy benefits claims.9 One study that attempted to address the issue of health plan utilization and cost of specialty drugs utilized medical and pharmacy administrative claims data from a Midwest healthcare plan to assess prevalence and trends for selected chronic conditions and their associated specialty drug use.⁹ RA was one of the 4 separate study cohorts (along with multiple sclerosis, psoriasis, and inflammatory bowel disease), with data on 4398 individuals identified within the RA cohort. The actual prevalence of RA was the highest among the 4 conditions studied, calculated to be 4489 per million members. Integration of medical and pharmacy benefits claims data was used to obtain a comprehensive understanding of the costs associated with RA and its associated specialty drug costs.⁹

Figure

The general results of the study demonstrated that, in 2010, among persons treated with a specialty drug, the annual specialty drug costs were more than 50% of the overall direct total cost of care. In patients with RA, the annual specialty drugs costs ($18,098) constituted 53% of the total per person per year (PPPY) total direct costs ($34,163). Across the entire population enrolled in that year (N = 979,735), the per member per year cost was highest for RA ($103.82) compared with the other conditions studied. The annual growth in PPPY cost of care from 2008 to 2010 for patients with RA was 8%, with an increase in specialty drug cost PPPY calculated to be 5.6% during the same time period (). A 9.7% increase in RA prevalence was found over the 3 years studied, although the actual use of specialty drugs to treat RA remained fairly stable during this period. Increased use of specialty drugs may not necessarily be associated with a change in disease prevalence, and specialty drug use tends to be condition-specific; however, it must be noted that new specialty drugs continue to emerge and may be expected to have high associated cost. Payers would expect that newer high-cost specialty agents would potentially prevent disability, leading to improved quality of life (QOL) and productivity in patients with chronic diseases. While evidence supporting such an assertion is lacking in some conditions (such as multiple sclerosis), specialty drugs used to treat RA have clinical trial data suggesting significantly delayed disease progression to disability and evidence for disease remission, although their incremental disease-modifying benefit over traditional therapies has not been fully elucidated.^9,12 As specialty drugs are a major factor in the rise in total cost of care of chronic conditions, including RA, both payers and providers must continue to diligently determine the comparative effectiveness of new and emerging agents versus existing therapies, and their appropriate place in the therapy armamentarium. Payers and providers must carefully analyze medical and pharmacy benefit drug cost trends and focus management activities on specialty agents in both benefit categories. Such management activities may include coordinated medical and pharmacy benefit formularies, specialty benefit designs, and specialty drug management programs, along with coordinating care management through the medical and pharmacy benefits to maximize the value and benefits that specialty drugs for RA may provide for patients affected by this disorder.⁹

Clinical and Economic Impact of RA-Associated Comorbidities

Along with considering the clinical impact of RA itself and its associated costs, other medical conditions and costs beyond the treatment of RA-associated joint disease may significantly impact patient management.¹ RA is a chronic disease characterized by both inflammation and alterations in immunity. In addition to the joints and the musculoskeletal system, RA can affect many organs, and its management may be impacted by these comorbidities. One study by Petri et al designed to assess this impact evaluated medical records for 62,681 patients with RA. A total of 6897 different ICD-9 diagnostic codes were recorded, of which 2220 occurred in 20 or more patients diagnosed with RA. The most predominantly identified registered comorbidities were cardiovascular in nature; specifically, hypertension not-otherwise specified (NOS; —20.4%), benign hypertension (19.9%), chest pain NOS (13.9%), and hyperlipidemia not-elsewhereclassified NOS (13.9%).¹³ Cardiovascular disease (CVD) has been recognized as the leading cause of death in patients with RA, with nearly 40% of mortality seen in these patients attributed to CVD.¹⁴ Patients with RA have a 2-fold increased risk for both myocardial infarction (MI) and stroke. This risk increases to nearly 3-fold in patients who have had RA for 10 years or more. The increased risk for CVD appears to occur independent of traditional CV risk factors.¹⁴ Within the Petri study, strong comorbidity associations with RA (relative risk, >3) were also found for psoriatic arthropathy, adverse reaction to medications/biologic agents, reaction to internal joint prosthesis, osteoporosis, idiopathic fibrosing alveolitis, osteomyelitis, immune deficiency, anemia, and Cushing’s syndrome. The spectrum of comorbidities associated with a particular disease is important to address both in terms of treatment of that condition and for potential future drug development. Therapeutic risk management in patients with RA necessitates a complete understanding of associated characteristics and comorbidities specific to these patients for whom a diseasemodifying therapy may be prescribed. A clear description of related comorbidities allows a better understanding of the patient population and potential treatment effectiveness and safety issues associated with therapy.¹³

The economic implications of comorbidities in patients with RA must also be considered for their potential impact on their care and outcomes. Associated CVD and other comorbidities may increase the overall costs associated with the management of RA. A study examining resource utilization and direct healthcare costs associated with comorbid CVD and depression in 10,298 patients with RA was performed by Joyce et al, using analyses of retrospective healthcare claims data.³ Of the patients studied, 8916 (86.6%) had RA alone while 608 (5.9%) were diagnosed with both RA and CVD. A total of 716 patients had RA plus depression (7.0%), with 58 patients diagnosed with all 3 conditions (0.5%). All patients with CVD and/ or depression incurred significantly higher follow-up costs when compared with those patients diagnosed only with RA. Adjusted mean annual healthcare costs were highest for the cohort with RA and CVD, with the next highest expenditures recorded for the patients with RA, CVD, and depression, followed by those with RA plus depression. Patients who had RA alone without these associated comorbidities had the lowest mean annual healthcare costs (Table). While the patients with RA and CVD and/ or depression had a higher rate of RA-related hospitalizations, adjusted RA-related healthcare costs did not reflect statistically significant differences compared with patients who had RA only. Overall, the study results demonstrated that the presence of the comorbidities studied added substantially to annual healthcare costs in patients with RA,³ and underscored the need for managed care clinicians and providers to carefully assess each patient with RA not only for their joint disease but also for coexisting comorbidities that might complicate both therapy and healthcare utilization. Doing so will better individualize patient care plans to optimize outcomes while managing associated costs.

Optimizing Access to Disease-Modifying Therapies

Patients with RA may have rapid declines in function that can begin early in the disease course. Disability increases most rapidly during the early years of the disease course, and, if patients are not accurately diagnosed and do not receive appropriate care early, substantial functional declines may result.¹⁵ However, despite the availability of evidence-based guidelines recommending early and aggressive treatment of active RA, populationbased studies of disease-modifying antirheumatic drug (DMARD) use in patients with RA continue to demonstrate low rates of actual receipt of DMARD therapy for these patients, ranging from only 30% to 71%.^16-22 A recent study examining this issue was conducted by Schmajuk et al to identify sociodemographic, community, and health plan factors associated with DMARD receipt in a Medicare managed care population.16 Individuallevel Healthcare Effectiveness Data and Information Set (HEDIS) statistics were analyzed for 93,143 patients with RA who were at least 65 years of age and had at least 2 diagnoses of RA within a measurement year in the period between 2005 and 2008. The largest difference in performance on the HEDIS RA measure was found to be related to age. Participants 85 years or older had a 30% lower rate of DMARD receipt. Other study categories associated with lower rates of DMARD receipt included male gender, individuals identified as black or “other” with respect to race, location in an area of lower socioeconomic status, and individuals in the middle or South Atlantic regions. Patients who lived in an area characterized by a shortage of healthcare professionals also had slightly lower DMARD performance (—3 percentage points). Of additional interest is the fact that those enrolled in a for-profit health plan also had a 4% lower rate of DMARD receipt compared with patients enrolled in a not-for-profit insurance plan. Performance tended to vary significantly by health plan, with performance rates ranging from 16% to 87% even after adjustments for case mix in the study. Overall, significant differences were found in DMARD receipt based on individual, community, and health plan characteristics. When taken into account with the massive individual and societal costs associated with RA and the increasing body of substantial evidence that DMARDS can reduce such costs, variations based on demographics, socioeconomic status, and location are not acceptable. Both clinicians and patients must be educated to improve therapy uptake and use to eliminate these disparities and potentially improve patient outcomes.¹⁶

Treatment paradigms for the management of RA have continually evolved over time. While past approaches focused on conventional DMARD therapy, the current treatment model centers on earlier, aggressive treatment with biologic DMARD therapies in combination with conventional DMARDs. Algorithms for therapy in early RA based upon both disease activity and features associated with poor disease prognosis to determine whether DMARD monotherapy, combination DMARD therapy (double/triple therapy), or DMARDs in combination with other agents, including biologic therapies, would be the best approach to treating individual patients in order to most effectively delay disease progression and disability (a treatment algorithm for early RA can be found in the companion article within this supplement, “Current Therapeutic Agents and Treatment Paradigms for the Management of Rheumatoid Arthritis”).^15,17

With updated treatment guidelines and protocols, managed care clinicians and providers face new challenges in selecting options for drug therapy for patients with RA. While guidelines recommend early and aggressive treatment, potentially including traditional and biologic DMARDs in combination, cost considerations complicate the therapy landscape.^15,17 The high costs associated with biologic therapies present substantial challenges to healthcare systems faced with limited resources. Despite guidelines and evidence, actual practice recommendations surrounding the use of biologic therapies can vary. Some analyses of the cost-effectiveness of biologic therapies have concluded that such treatments should be used only after therapy with less expensive conventional DMARDs and other agents has failed. This recommendation is based on the concept that optimizing relatively low-cost therapy to prolong disease control and improve patient outcomes in RA may delay the need for use of biologic DMARDs, resulting in cost savings.²³ Data have demonstrated that combination (triple) therapy with conventional agents may provide outcomes similar to those seen with biologic therapies while keeping costs in check. For example, O’Dell and colleagues assessed RA patients with active disease despite methotrexate therapy who were assigned to receive either triple therapy (methotrexate, sulfasalazine, hydroxycholoroquine) or the biologic agent etanercept plus methotrexate.²⁴ Those who did not demonstrate significant improvement in disease activity scores by week 24 were switched in blinded fashion to the other therapy. Results demonstrated that both groups showed significant improvement over the first 24 weeks. A total of 27% of patients in each cohort required a switch in treatment at 24 weeks. The response after switching did not differ significantly between the 2 groups. Overall, the change in the disease activity scores between baseline and 48 weeks was similar in both cohorts. Results suggested that, with respect to clinical benefit, triple therapy with conventional agents was noninferior to combination methotrexate and etanercept. Using triple therapy first and switching to a biologic agent only in those patients who do not respond adequately to triple therapy may allow a significant number of patients to be treated in a more cost-effective manner while still achieving desired outcomes. While costs are a strong consideration, biologic agents are transforming the practice of medicine in general, improving survival rates, delaying or halting disease progression, and improving patient QOL. The expanding indications for use of biologics present several positive aspects for managed care clinicians and providers. These include the potential for increased leverage with contracting as new agents enter an already packed playing field, known pricing based on previous indications for an agent, and large populations of users experienced with the drug, which can help to alleviate safety concerns. In addition, the possibility of accruing multiple clinical benefits from such therapies in patients with multiple comorbid conditions, and the ability to gauge real practice use surrounding issues regarding dosing and concurrent/combination therapies from existing payer databases, may contribute to an ability to incorporate biologic agents into therapy protocols more optimally.5 For example, one landmark study by Greenberg et al examined the association of CV events with tumor necrosis factor (TNF) antagonist therapy compared with non-biological DMARD therapy in patients with RA.25 This study assessed more than 10,000 registry-registered patients in 3 study cohorts of patients receiving a TNF antagonist, methotrexate, or other non-biologic DMARDs. The primary outcome was a composite of non-fatal MI, transient ischemic attack or stroke, and CV-related death. After adjusting for age, gender, CV risk factors, and characteristics of each patient’s RA disease, study results demonstrated that those patients who received a biologic TNF antagonist had a reduced risk of the primary composite CV end point compared with patients in the non-biologic DMARD cohorts. These results suggested the potential advantages of biologic therapy in managing both RA and associated comorbidities.²⁵

Managed care plans can effectively manage use of biologic therapies in several ways. First, all classes of biologic DMARDs should be available for prescribing to patients with RA. Because of limited potential for efficacy, plans should consider limiting the number of switches between agents in the same class.¹⁵ Updated 2012 American College Rheumatology recommendations established an algorithm for drug changes and switches in patients with established RA, including switches among DMARDs, switching to biologic DMARDs, and among biologic DMARDs because of lack or loss of efficacy or adverse events.¹⁷ A disease management approach should be designed to appropriately measure patient outcomes. Managed care payers and providers will also need to follow costs associated with therapy and assist patients with therapy adherence to maximize treatment benefits.¹⁵

Optimizing Adherence to RA Therapy

Adherence to therapy is another important issue for consideration in the context of managed care as the full benefits of therapy, especially with biologic DMARDs, can be achieved only if patients are compliant with therapy and adhere to their prescribed treatment regimens.^26,27 Factors that can negatively impact therapy adherence and persistence include drug efficacy, serious adverse effects/ events, injection site issues, patients’ initial expectations of therapy and perception of the burden of treatment, and out-of-pocket expenses for therapy. Healthcare providers play an important role in influencing patient understanding of therapy and in promoting adherence to proper utilization of treatments for RA.^26,28,29 One method that may assist in promoting adherence to therapy is enrolling patients receiving specialty pharmacy services into RA disease therapy management (DTM) programs. A study by Stockl et al evaluated this technique among patients with an RA diagnosis and a pharmacy claim for an injectable RA agent over a 1-year period between 2007 and 2008. Patients were categorized into 1 of 3 groups: 1) patients prescribed an injectable RA drug though a specialty pharmacy with participation in the DTM program; 2) patients prescribed through a specialty pharmacy without DTM; and, 3) patients prescribed RA treatment at a community pharmacy without specialty pharmacy involvement. Routine services for patients receiving their prescriptions through a specialty pharmacy included a patient welcome brochure detailing drug ordering, storage and monitoring, and proper disposal of ancillary supplies along with direct mail refill service, refill reminders, patient care coordination, and 24-hour/7-day-per-week pharmacist access. The DTM program added a patient-centric model to coordinate care interventions and communications relying on patient self-management, and to provide education and clinician support to allow patients to develop self-management skills surrounding their symptoms and therapy. Of specialty pharmacy patients, 14.2% chose DTM participation. Results demonstrated that adherence to treatment with any injectable RA medication was significantly higher for those patients entering the DTM program, the intent-to-treat (ITT) DTM cohort (mean proportion of days covered [PDC] = 0.83), and for the patients who completed the RA DTM program, the completer cohort (PDC = 0.89) compared with those in the community pharmacy cohort (PDC = 0.60). Compared with those who received specialty pharmacy services without DTM, the DTM completer cohort had significantly greater adherence (P <.001) to treatment, although the ITT DTM group was not significantly different (P = .291). It must, however, be noted that patients in the DTM cohort did incur higher pharmacy costs during the study period, and costs must be taken into consideration with any special adherencedirected programs or efforts. It is also important to note that the DTM cohort consisted of the 14.2% of patients who chose to participate in the DTM program and completed it. As such, there may have been potential selection bias favoring more compliant patients being included within this group.²⁶

Optimizing Patient Outcomes Through Care Coordination

Optimal coordination of care can present a significant conundrum to managed care professionals. As RA is a disease characterized by multiple complications and comorbidities, managed care clinicians and providers must remain aware of the potential for uncomfortable and even unsafe care transitions, lack of communication among a patient’s many care providers, and suboptimal resource utilization in these patients. One set of models that has been suggested involves the synchronization of care via interprofessional coordinated care models rather than the standard rheumatologist-centered treatment paradigm. Such models are focused on shared power and authority and mutual respect for each participant’s professional abilities. Effective cooperation among the patient, providers, health systems, and employers in this coordinated care model offers the unique promise for both improving outcomes and eliminating service duplication and redundancies while minimizing waste. While such models may vary by payer/provider, they should all strive to reduce hospital readmission rates caused by medication errors, improve compliance with and adherence to treatment plans, and provide formal follow-up care to patients. Various interprofessional models may be pertinent to RA management, including³⁰:

• Specialized arthritis programs based on primary care referral to a specialist with additional healthcare referrals as needed to promote high-quality care, education, and access to a varied range of services
• The ongoing management model, in which providers expand their clinical roles, working with specialists and extended role providers (ERPs); other clinicians to facilitate maintenance of care
• The triage model, providing a primary care physician for consultation and ERPs to conduct assessments; this model may include additional rural consultation/telemedicine models to serve specific populations

While the use of such models is supported by the chronic nature of RA and patient needs, there is still a lack of current data surrounding the cost-effectiveness of their outcomes, which prevents definitive conclusions about their potential outcomes. New studies are needed to identify best practices in this area as well as strategies for implementing interprofessional care coordination models to provide appropriate strategies geared toward patients and their care providers to optimize both practices and outcomes, along with cost-effectiveness.³⁰

Conclusion

Management of RA remains a significant challenge for managed care clinicians, providers, and patients with this disease. Comorbidities, multiple therapy choices, and continually evolving recommendations for therapy, along with cost considerations, substantially complicate strategies to optimize care and improve outcomes in patients with RA. Managed care organizations must continue to explore new data and approaches to find the most clinically effective and cost-conscious options designed to improve disease management and care coordination for these patients. By working together with their fellow healthcare professionals to create coordinated care models to optimize management, managed care professionals will be better able to work with their patients with RA to improve collaboration and outcomes of care.Author affiliation: Gary Owens Associates, Ocean View, DE.

Funding source: This activity is supported by an educational grant from Antares Pharma, Inc.

Author disclosures: Dr Owens reports serving as a consultant for AbbVie, Crescendo Bioscience, Inc, and Johnson & Johnson.

Authorship information: Concept and design; drafting of the manuscript; and critical revision of the manuscript for important intellectual content.

Address correspondence to: gowens99@comcast.net

1. Cardarelli WJ. Implications for managed care and specialty pharmacy in rheumatoid arthritis. Am J Manag Care. 2012; 18(suppl 13):S315-S324.
2. Fautrel B, Verstappen SM, Boonen A. Economic consequences and potential benefits. Best Pract Res Clin Rheumatol. 2011;2 5:607-624.
3. Joyce AT, Smith P, Khandker R, Melin JM, Singh A. Hidden cost of rheumatoid arthritis (RA): estimating cost of comorbid cardiovascular disease and depression among patients with RA. J Rheumatol. 2009;36(4):743-752.
4. Cooper NJ. Economic burden of rheumatoid arthritis: a systematic review. Rheumatology (Oxford). 2000;39(1):28-33.
5. Cohen M, Morrow T, Penna P. Managing the expanded use of biologics across therapeutic areas: an example from b-cell targeted therapies. Am J Manag Care. 2006;12(suppl 2):S24-S37.
6. Kvien TK. Epidemiology and burden of illness of rheumatoid arthritis. Pharmacoeconomics. 2004;22(2, suppl 1):1-12.
7. Fautrel B, Clarke AE, Guillemin F, et al. Costs of rheumatoid arthritis: new estimates from the human capital method and comparison to the willingness-to-pay method. Med Decis Making. 2007;27(2):138-150.
8. Bansback N, Marra CA, Finckh A, Anis A. The economics of treatment in early rheumatoid arthritis. Best Prac Res Clin Rheumatol. 2009;23(1):83-92.
9. Gleason PP, Alexander GC, Starner CI, et al. Health plan utilization and costs of specialty drugs within 4 chronic conditions. J Manag Care Pharm. 2013;19(7):542-548.
10. Sullivan SD. The promise of specialty pharmaceuticals: are they worth the price? J Manag Care Pharm. 2008;14(4, suppl S): S3-S6.
11. Johnson S, Gunderson B, Bowen KL, Starner CI, Gleason PP. Specialty drugs are forecasted to be 50% of all drug expenditures in 2018 (abstract). J Manag Care Pharm. 2013;19(2):187.
12. Chen YF, Jobanputra P, Barton P, et al. A systematic review of the effectiveness of adalimumab, etanercept and infliximab for the treatment of rheumatoid arthritis in adults and an economic evaluation of their cost-effectiveness. Health Technol Assess. 2006;10(42):iii-iv,xi-xiii,1-229.
13. Petri H, Maldonato D, Robinson NJ. Data-driven identification of comorbidities associated with rheumatoid arthritis in a large US health plan claims database. BMC Musculoskelet Disord. 2010;11:247. doi:0.1186/1471-2474-11-247.
14. Dhawun SS, Quyyumi AA. Rheumatoid arthritis and cardiovascular disease. Curr Atherscler Rep. 2008;10(2):128-133.
15. Owens GM. New approaches for the management of rheumatoid arthritis. J Manag Care Med. 2013;16(4):31-35.
16. Schmajuk G, Trivedi AN, Solomon DH, et al. Receipt of disease-modifying antirheumatic drugs among patients with rheumatoid arthritis in Medicare managed care plans. JAMA. 2011;305(5):480-486.
17. Singh JA, Furst DE, Bharat A, et al. 2012 Update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken). 2012;64(5):625-639.
18. Edwards CJ, Arden NK. Fisher D, et al. The changing use of disease-modifying anti-rheumatic drugs in individuals with rheumatoid arthritis from the United Kingdom General Practice Research Database. Rheumatology (Oxford). 2005:44(11): 1394-1398.
19. Schmajuk G, Schneeweiss S, Katz JN, et al. Treatment of older adult patients diagnosed with rheumatoid arthritis: improved but not optimal. Arthritis Rheum. 2007;57(6):928-934.
20. Khanna R, Smith MJ. Utilization and costs of medical services and prescription medications for rheumatoid arthritis among recipients covered by a state Medicaid program: a retrospective, cross-sectional, descriptive, database analysis. Clin Ther. 2007;29(11):2456-2467.
21. Grijalva CG, Chung CP, Stein CM, Mitchel EF Jr, Griffin MR. Changing patterns of medication used in patients with rheumatoid arthritis in a Medicaid population. Rheumatology (Oxford). 2008;47(7):1061-1064.
22. Widdifield J, Bernatsky S, Paterson JM, et al. Quality care in seniors with new-onset rheumatoid arthritis: a Canadian perspective. Arthritis Care Res (Hoboken). 2011;63(1):53-57.
23. Fautrel B. Economic benefits of optimizing anchor therapy for rheumatoid arthritis. Rheumatology(Oxford). 2012;51(suppl 4): iv21-iv-26.
24. O’Dell JR, Mikuls TR, Taylor TH, et al; for the CSP 551 RACAT Investigators. Therapies for active rheumatoid arthritis after methotrexate failure. N Eng J Med. 2013;369(4):307-318.
25. Greenberg JD, Kermer JM, Curtis JR, et al. Tumour necrosis factor antagonist use and associated risk reduction of cardiovascular events among patients with rheumatoid arthritis. Ann Rheum Dis. 2011;70(4):576-582.
26. Stockl KM, Shin JS, Lew HC, et al. Outcomes of a rheumatoid arthritis disease therapy management program focusing on medication adherence. J Manag Care Pharm. 2010;16(8):593-604.
27. Grijalva CG, Chung CP, Arbogast PG, et al. Assessment of adherence to and persistence on disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis. Med Care. 2007;45:(10, suppl 2): S66-S76.
28. Brod M, Rousculp M, Cameron A. Understanding compliance issues for daily self-injectable treatment in ambulatory care settings. Patient Prefer Adherence. 2008;2:129-136.
29. Curkendall S, Patel V, Gleeson M, et al. Compliance with biologic therapies for rheumatoid arthritis: do patient out-of-pocket payments matter? Arthritis Rheum. 2008;59(10):1519-1526.
30. Marion CE, Balfe LM. Potential advantages of interprofessional care in rheumatoid arthritis. J Manag Care Pharm. 2011;17(9, suppl B):S25-S29.

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