Original article
`
`Biologics utilization for rheumatoid
`arthritis in the United States: An
`observational longitudinal study
`
`Journal of Medical Marketing
`13(2) 74–81
`! The Author(s) 2013
`Reprints and permissions:
`sagepub.co.uk/journalsPermissions.nav
`DOI: 10.1177/1745790413480520
`mmj.sagepub.com
`
`Maria Goutsou1,*, Ozgecan Uluscu1,*, Angela Amend Kwasnik2,
`Robert Stianchi2, Paul M Peloso3 and Gillian Cannon2,*
`
`Abstract
`We describe patterns of treatment of rheumatoid arthritis with biologics in the United States during
`2000–2010 using longitudinal data in the IMS LifeLinkTM health plan claims database. Rheumatoid arthritis
`prevalent and incident cases were identified by ICD-9 diagnostic codes. The proportion of prevalent rheuma-
`toid arthritis cases using biologics increased from 18.7% in 2005 to 26.3% in 2010. Tumor necrosis factor a
`antagonists constituted 99.1% of biologics in 2005 and 84.4% in 2010. During 2000–2010, 58.1% of incident
`cases were treated with 1st-line non-steroidal anti-inflammatory drugs and/or corticosteroids and 36.5%
`were treated with 1st-line synthetic disease-modifying anti-rheumatic drugs. Biologics constituted 5.4% of
`1st-line therapies for incident rheumatoid arthritis cases and 30.9%–56.3% of 2nd-to-5th line therapies. For
`those who started on 1st-line non-steroidal anti-inflammatory drugs/corticosteroids, the duration of pharma-
`cotherapy before switching to biologics was 7.2 years for those starting biologics in 2005–2007 and 4.2 years
`for those starting biologics in 2008–2010. In summary, the use of biologics as 1st-line treatment for rheuma-
`toid arthritis remained relatively constant at about 5%, but the durations of treatment with other pharma-
`cotherapies before starting biologics shrank.
`
`Keywords
`Rheumatoid arthritis, biologics, time trends, TNF-a antagonists, line of therapy, longitudinal
`
`Introduction
`
`Rheumatoid arthritis (RA) is an autoimmune disease
`in which chronic inflammation in the synovium causes
`pain, progressive destruction of the joints, and disabil-
`ity.1 Estimates of the prevalence of RA in the US adult
`population range from 0.6% to 1.1%.2,3 The age of
`disease onset is typically in the fifth decade of life
`and both prevalence and incidence rates are 2- to
`4-fold higher in women than in men.4,5 The direct
`and indirect societal costs of RA in the United States
`are estimated to be $8.4 billion and $10.9 billion,
`respectively, in 2005 dollars, totalling $19.3 billion.6
`Non-steroidal anti-inflammatory drugs (NSAIDs)
`are frequently used to control pain in early or mild dis-
`ease.7 Low-dose corticosteroids, i.e., prednisone, pred-
`nisolone, or methylprednisolone usually administered
`orally, but occasionally via intra-articular, intramuscu-
`lar, or intravenous routes, are used in short courses to
`reduce inflammation.7,8 Drugs that slow the progres-
`sion of joint erosion are known as disease-modifying
`
`anti-rheumatic drugs (DMARDs). The traditional
`DMARDs are synthetic chemicals—methotrexate,
`hydroxychloroquine,
`leflunomide, sulfasalazine, and
`parenteral gold.7,8 More recently, several biologic
`drugs have been approved for the treatment of RA,
`and they also have demonstrated disease-modifying
`abilities. The biologics are protein macromolecules
`that act at various points in the immune and inflamma-
`tory responses. They belong to several classes,
`most prominently the tumor necrosis factor (TNF)-a
`
`1C1 Consulting Summit, NJ, USA
`2Merck & Co., Inc., Whitehouse Station, NJ, USA
`3Merck & Co., Inc., Kenilworth, NJ, USA
`
`*Currently at Otsuka America Pharmaceutical Inc., Princeton, NJ,
`USA.
`
`Corresponding author:
`Gillian Cannon, Otsuka America Pharmaceutical Inc., 1 University
`Square Drive Suite 500, Princeton, NJ 08540, USA.
`Email: gillian.cannon@otsuka-us.com
`
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`Goutsou et al.
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`75
`
`antagonists. The TNF-a antagonists—adalimumab,
`certolizumab pegol, etanercept, golimumab, and
`infliximab—produce their primary effect by blocking
`TNF from interacting with cell surface TNF receptors.
`There are several other classes of biologics. Anakinra
`and tocilizumab are inhibitors of the cytokines interleu-
`kin-1 and interleukin-6, respectively. Abatacept inhibits
`T-cell activation, while rituximab acts to reduce circu-
`lating CD20 + B-cells.
`Guidelines in the United States recommend bio-
`logics as 2nd-line treatment, following traditional syn-
`thetic DMARDs, for established RA.9,10 Biologics are
`also recommended as an option for 1st-line treatment
`of early RA in patients with high disease activity and
`features of poor prognosis.9,10 Cross-sectional studies
`of US health insurance claims data in 2001–2004 indi-
`cated that 12%–14% of RA patients used biologics,
`predominantly TNF-a antagonists,11,12 but there is
`comparatively little information about how biologics
`are used to treat RA in the United States.
`The objective of this study was to determine pat-
`terns of biologic use by RA patients, in terms of: (1)
`time trends in the prevalence of biologics use; (2) bio-
`logic, synthetic DMARD, and symptom-modifying
`drug use by line of treatment of incident RA cases;
`and (3) the duration of treatment of incident RA
`cases with non-biologics (NSAIDs, corticosteroids,
`and synthetic DMARDs) before beginning a biologic.
`
`Methods
`Study design
`
`This is a descriptive analysis of longitudinal data in the
`IMS LifeLinkTM health plan claims database for years
`2000–2010. IMS LifeLinkTM is a database of fully
`adjudicated medical and pharmaceutical claims for
`over 70 million patients in 75 health plans across the
`United States. The database comprises linked data sets
`of patient demographics and eligibility information,
`diagnostic (ICD-9-CM) and procedural (CPT-4 and
`HCPCS) codes for each patient encounter, and retail
`and mail order prescription records containing the
`NDC code and the quantity of
`the medication
`dispensed.
`
`Study sample
`
`Biologic utilization was determined for two patient
`samples: the prevalent sample,
`in which RA cases
`were identified for each calendar year from 2005 to
`2010, and an incident sample,
`in which incident
`cases occurring between January 1, 2001, and
`December 31, 2009, were followed longitudinally.
`For both samples, the date of the first occurrence of
`
`an RA diagnostic code was designated the index date.
`Prevalent RA cases were identified as of January 1 of
`each calendar year from 2005 to 2010. Incident RA
`cases had an index RA diagnosis between January 1,
`2001, and December 31, 2009.
`RA cases were identified by an ICD-9 diagnostic
`code for RA (ICD-9 714, 714.0, 714.2, 714.4,
`714.9). Prevalent RA cases were adults at least 18
`years of age on January 1 of the measurement year,
`with continuous enrolment and no RA medical claim
`for the 6 months prior to the index date. Incident cases
`were adults at least 18 years of age on the index date,
`with continuous enrolment and no RA medical claims
`for 12 months prior to the index date. Both prevalent
`and incident cases were also required to have either
`an RA medical claim or a prescription for an RA
`medication (a corticosteroid, DMARD, or biologic,
`identified by NDC code as well as HCPCS and
`Õ
`Drug and Product Codes) in the 12 months
`CPT
`following the index date.
`
`Data analysis
`
`The proportions of RA prevalent cases using biologics
`were computed for each calendar year from 2005 to
`2010 and projected onto the US population of RA
`patients. Drug category (NSAIDs/corticosteroids, syn-
`thetic DMARDs, biologics) use by incident RA cases
`
`was calculated by treatment line (1st through 5th
`
`line). The duration of treatment before commencing
`biologic drug therapy was computed for RA incident
`cases by 1st-line drug category (NSAIDs/corticoster-
`oids, synthetic DMARDs, biologics).
`Prevalent cases were analyzed for each calendar
`year from 2005 to 2010. Patient age was calculated
`from the patient’s date of birth. The presence of
`selected co-morbidities was based on pharmacy and/
`or medical claims in the period between the index
`date and the end of
`the measurement year(s).
`Pharmacy claims were used for medications
`for
`hypertension, hyperlipidemia, diabetes, and depres-
`sion. Rates of use of biologics were projected from
`prevalent cases to the US population of adults with
`RA. This projection was based on sales of biologics in
`the United States, using data in the IMS MIDASÕ
`drug sales database for 2005–2010. The projection
`was based on a four-step calculation as follows. In
`step 1, the average cost per patient of each biologic
`was determined for each year. The average cost per
`patient
`represented actual utilization taking into
`account medication adherence, persistency,
`and
`dose changes. In step 2, the number of patients in
`the United States taking each biologic was calculated
`by dividing the total US sales of each biologic by
`the average cost per patient determined in step 1.
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`76
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`Journal of Medical Marketing 13(2)
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`In step 3, the percent of patients using each biologic
`who had RA was calculated from the US prevalence
`of adult RA3 and number of US patients taking each
`biologic calculated in step 2. Finally, in step 4, the
`numbers of US RA patients taking each biologic were
`summed to calculate their total biologic use.
`Incident cases of RA were followed from the index
`date to either the end of the study period (December
`31, 2010), disenrollment from the health plan, or
`death. The sequence of drug therapies following the
`index date was determined by drug category,
`i.e.,
`NSAIDs/corticosteroids, synthetic DMARDs, and bio-
`logics. If patients used drugs from more than one cat-
`egory
`concomitantly,
`a hierarchical
`system of
`assignment was applied:
`if NSAIDs/corticosteroids
`and synthetic DMARDs were used concomitantly, the
`treatment was assigned to DMARDs; if biologics were
`used concomitantly with synthetic DMARDs and/or
`NSAIDs/corticosteroids, the treatment was assigned
`
`to biologics. In the first analysis, the percentage of
`patients on each category of RA drug was determined
`
`by line of therapy: 1st through 5th line. In the second
`
`treatment with
`the average duration of
`analysis,
`NSAIDs/corticosteroids
`and/or DMARDs before
`progressing to a biologic drug was determined.
`Kaplan-Meier survival plots with right censoring were
`conducted for time-to-event analyses, to estimate mean
`durations of biologic and non-biologic treatments.
`To examine time trends, this analysis was conducted
`for years 2000–2010, 2005–2007, and 2008–2010.
`
`Results
`Patient characteristics
`
`The characteristics of the prevalent RA population
`samples
`for years 2005–2010 are presented in
`Table 1. Patient characteristics remained relatively
`
`Table 1. Characteristics of prevalent rheumatoid arthritis (RA) cases in the IMS LifeLinkTM database in 2005–2010,
`by year
`
`2005
`(N¼ 16,093)
`
`2006
`(N¼ 27,636)
`
`2007
`(N¼ 42,628)
`
`2008
`(N¼ 67,544)
`
`2009
`(N¼ 82,683)
`
`2010
`(N¼ 76,049)
`
`Female (%)
`Age (years)
`Mean
`Median
`Age category (%)
`18–25
`26–35
`36–45
`46–55
`56–65
`>65
`Geographic region (%)
`East
`Midwest
`South
`West
`Comorbidities (%)
`Hypertension
`Hyperlipidemia
`Depression
`Arthralgia
`Osteoarthritis
`Psoriatic arthritis
`Diabetes
`Fibromyalgia
`Anemia
`Ankylosing spondylitis
`
`72.4
`
`57.4
`57.0
`
`1.7
`4.1
`12.1
`25.8
`32.9
`23.4
`
`25.2
`40.3
`24.1
`10.4
`
`34.7
`25.9
`10.0
`16.4
`15.9
`4.0
`13.8
`4.8
`7.2
`1.6
`
`72.3
`
`57.2
`57.0
`
`1.8
`4.3
`12.3
`26.0
`32.4
`23.2
`
`25.9
`36.6
`26.6
`10.9
`
`35.9
`27.6
`11.6
`17.8
`16.3
`3.7
`14.0
`5.0
`7.5
`1.8
`
`72.4
`
`56.7
`57.0
`
`2.0
`4.7
`12.9
`26.5
`31.9
`22.1
`
`28.1
`33.0
`27.4
`11.5
`
`36.8
`29.2
`12.5
`19.6
`16.8
`3.6
`14.7
`5.5
`8.3
`1.9
`
`72.4
`
`56.2
`56.0
`
`2.1
`5.2
`13.4
`26.8
`30.9
`21.6
`
`26.3
`32.5
`29.6
`11.6
`
`37.0
`29.6
`12.4
`21.1
`17.3
`3.6
`14.9
`6.1
`8.9
`2.0
`
`72.6
`
`57.1
`57.0
`
`2.0
`4.9
`12.9
`25.6
`30.2
`24.5
`
`28.5
`28.1
`33.5
`10.0
`
`38.5
`31.6
`12.9
`22.4
`18.3
`3.5
`15.3
`6.6
`9.5
`2.1
`
`72.7
`
`56.4
`56.0
`
`2.0
`5.2
`13.2
`26.5
`31.0
`22.1
`
`14.9
`32.7
`40.5
`11.9
`
`37.9
`31.1
`14.5
`24.0
`17.5
`3.8
`14.9
`7.3
`9.5
`2.2
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`Goutsou et al.
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`77
`
`constant during this time period. The proportion of
`female patients stayed with the range of 72.3%–
`72.7% and the mean age in the range 56.2–57.4
`years. Comorbidities varied little, with the most fre-
`quent comorbidity, hypertension, remaining in the
`range of 34.7%–38.5% of patients. The patient N
`increased from 16,093 in 2005 to 76,049 in 2010
`and the geographic distribution of patients varied,
`reflecting changes in the health plan composition of
`the IMS LifeLinkTM database.
`The characteristics of incident RA cases treated
`with biologics in time periods 2000–2010, 2005–
`2007, and 2008–2010 are presented in Table 2. In
`the period 2000–2010 the proportion of female RA
`patients was 71.6%, the mean age at diagnosis was
`54.0 years, and the most common comorbidity was
`hypertension (37.0%). The characteristics of RA inci-
`dent cases treated with biologics remained essentially
`the same in the two time periods 2005–2007 and
`2008–2010.
`
`Table 2. Characteristics of incident rheumatoid arthritis
`(RA) cases treated with biologics in the IMS LifeLinkTM
`database in 2000–2010, 2005–2007, and 2008–2010
`
`2000–2010
`(N¼ 131,797)
`
`2005–2007
`(N¼ 46,440)
`
`2008–2010
`(N¼ 62,009)
`
`71.6
`Female (%)
`54.0
`Age at diagnosis, years
`54.0
`Mean
`54.0
`Median
`Age category at diagnosis (%)
`18–25
`2.2
`26–35
`7.3
`36–45
`16.4
`46–55
`28.6
`56–65
`27.5
`>65
`17.9
`Geographic region (%)
`East
`Midwest
`South
`West
`Comorbidities (%)
`Hypertension
`Hyperlipidemia
`Arthralgia
`Depression
`Osteoarthritis
`Diabetes
`Anemia
`Fibromyalgia
`Psoriatic arthritis
`Ankylosing spondylitis
`
`37.0
`30.5
`25.6
`19.4
`18.3
`14.3
`9.3
`7.6
`3.8
`2.4
`
`21.6
`33.2
`35.8
`9.5
`
`71.9
`53.8
`53.8
`54.0
`
`2.3
`7.3
`16.4
`29.1
`28.2
`16.6
`
`23.6
`30.5
`35.8
`10.2
`
`37.2
`30.5
`23.3
`18.9
`17.3
`14.4
`8.9
`6.5
`3.5
`2.3
`
`71.2
`54.3
`54.3
`54.0
`
`2.2
`7.3
`16.0
`28.2
`27.3
`19.1
`
`21.5
`31.4
`37.2
`10.0
`
`38.6
`32.8
`29.7
`20.0
`20.2
`14.8
`10.2
`9.3
`4.0
`2.6
`
`Time trends in use of biologics
`
`The proportion of prevalent RA cases using biologics,
`projected to the US population, increased from 18.7%
`in
`2005
`to
`26.3% in
`2010
`
`(N¼ 249,611)
`(N¼ 370,142) (Figure 1). TNF-a antagonists were
`
`frequently used biologics, constituting
`the most
`99.1% of biologics in 2005 and 84.4% in 2010, as
`projected to the US population. Among the TNF-a
`antagonists, the most frequently used were etanercept
`(9.4%), infliximab (6.2%), and adalimumab (5.4%),
`with golimumab (0.6%) and certolizumab (0.6%)
`beginning to be used in 2009 (Figure 2). Other bio-
`logics used in 2010 were abatacept (2.5%), rituximab
`(1.2%), anakinra (0.1%), and tocilizumab (0.3%).
`
`Use of biologics by line of treatment
`
`The use of biologics and other drug categories by line
`of therapy is shown in Figure 3. The 1st-line therapies
`of most incident cases were NSAIDs/steroids (58.1%)
`or synthetic DMARDs (36.5%). Biologics constituted
`5.4% of 1st-line therapies for incident RA cases, and
`30.9%, 49.5%, 56.3%, and 55.2%, respectively, of
`
`2nd-, 3rd-, 4th-, and 5th-line therapies.
`
`Time until initiating biologics
`
`The time lapse between RA diagnosis and initiation of
`biologics is shown in Figure 4, by category of 1st-line
`treatment. In the period 2000–2010 (Figure 4, upper
`panel), there was an initial period of 0.1–0.3 years
`without any pharmacological treatment for RA. The
`most common treatment strategy (58.1% of patients)
`was 1st-line treatment with NSAIDs/corticosteroids,
`for an average of 5.7 years, followed by treatment
`with synthetic DMARDs, for an average of 4.1 years,
`totalling 9.8 years of pharmacotherapy before begin-
`ning biologics. Patients who were treated with
`DMARDs as 1st-line therapy (36.5%) spent an aver-
`age of 4.8 years on DMARDs before initiating
`biologics.
`The percentage of incident RA cases using biologics
`as 1st-line therapy was 5.4% in 2000–2010 and
`remained constant at 5.4% in the periods 2005–2007
`and 2008–2010. However, the durations of pharmaco-
`
`therapy before initiating biologics as 2nd-line treat-
`
`in the
`ment decreased during the decade. Hence,
`period 2008–2010, patients who initiated pharmaco-
`therapy with an NSAID/corticosteroid spent a total of
`only 4.2 years on pharmacotherapies (2.2 years on
`NSAIDs/corticosteroids, 2.0 years on synthetic
`DMARDs) before initiating biologics
`(Figure 4,
`lower panel), and those who initiated with a synthetic
`DMARD spent only 2.4 years before initiating a bio-
`logic (Figure 4, lower panel). This is compared to 7.2
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`78
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`Journal of Medical Marketing 13(2)
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`Biologic No biologic
`
`81.3
`
`78.1
`
`77.1
`
`76.1
`
`75.9
`
`73.7
`
`18.7
`
`2005
`
`21.9
`
`2006
`
`22.9
`
`2007
`
`23.9
`
`2008
`
`24.1
`
`2009
`
`26.3
`
`2010
`
`Year
`
`100
`90
`80
`70
`60
`50
`40
`30
`20
`10
`0
`
`Percent RA patients
`
`Figure 1. Proportion of prevalent rheumatoid arthritis (RA) cases using biologics in 2005–2010, by year, projected to the
`US population.
`
`Tocilizumab
`Anakinra
`Rituximab
`Abatacept
`Certolizumab
`Golimumab
`Adalimumab
`Infliximab
`Etanercept
`
`21.9%
`0.2
`0.3
`0.5
`
`22.9%
`0.1
`0.5
`1.1
`
`23.9%
`0.1
`0.8
`
`1.9
`
`4.8
`
`5.1
`
`5.3
`
`7.7
`
`7.1
`
`6.3
`
`18.7%
`0.2
`
`3.3
`
`7.0
`
`26.3%
`0.3
`0.1
`1.2
`
`2.5
`
`0.6
`0.6
`
`5.4
`
`6.2
`
`24.1%
`0.1
`1.0
`
`2.4
`0.2
`0.4
`
`5.5
`
`5.8
`
`8.2
`
`8.4
`
`8.8
`
`9.4
`
`8.8
`
`9.4
`
`2005
`
`2006
`
`2007
`
`2008
`
`2009
`
`2010
`
`Year
`
`30
`
`25
`
`20
`
`15
`
`10
`
`5
`
`0
`
`Percent RA patients
`
`Figure 2. Proportion of prevalent rheumatoid arthritis (RA) cases using biologics in 2005–2010, by biologic and by year,
`projected to the US population.
`
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`Goutsou et al.
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`79
`
`Biologics
`DMARDs
`NSAIDs/Steroids
`
`N=131,797
`5.4
`
`N=30,802
`
`N=8,112
`
`N=2,122
`
`N=719
`
`36.5
`
`58.1
`
`30.9
`
`49.5
`
`56.3
`
`55.2
`
`48.1
`
`11.7
`
`38.8
`
`21.1
`
`25.8
`
`17.9
`
`24.1
`
`20.7
`
`1st line
`
`2nd line
`
`3rd line
`Treatment
`
`4th line
`
`5th+ line
`
`100
`90
`80
`70
`60
`50
`40
`30
`20
`10
`0
`
`Percent RA patients
`
`Figure 3. Drug class utilization by incident rheumatoid arthritis (RA) cases in the IMS LifeLinkTM database in 2001–2010,
`by line of treatment.
`
`years for those who started on NSAIDs/corticosteroids
`and 3.7 years for those who started on synthetic
`DMARDs, before receiving a biologic in the 2005–
`2007 timeframe (Figure 4, middle panel).
`
`Discussion
`
`The data in IMS LifeLinkTM indicate that an increas-
`ing number of prevalent RA cases received biologics
`during the study period, from less than 20% in 2000 to
`over 25% in 2010. This is consistent with a time trend
`of gradually increasing biologic use in the decade since
`year 2000. Cross-sectional studies reporting biologic
`drug use in the earlier part of the decade are consistent
`with this time trend. In studies of MarketScan admin-
`istrative data for 2001–2004 and a state Medicaid pro-
`gram (West Virginia) for 2003, biologics were used to
`treat, respectively, 14.8% (TNF-a antagonists, 13.5%;
`other biologics, 1.3%) and 12% of RA patients.11,12
`These two studies reported data for 7965 and 1157
`RA patients, respectively. In two smaller studies of
`about 300–330 RA patients in the United States, the
`percentages treated with biologics were 28.8% in 2006
`and 33% in 2005–2008.13,14
`In this study, the percentage of patients treated with
`biologics as 1st-line treatment was 5.4%. This percent-
`age remained constant in the periods 2000–2010,
`2005–2007, and 2008–2010, suggesting a consistency
`of use for a select subset of RA patients. This is likely
`in accord with US guidelines recommending biologics
`as 1st-line treatment only for the minority of early RA
`patients with high disease activity and features of poor
`
`prognosis.9,10 Consistent with biologics use as 2nd-
`
`line therapy, cross-sectional studies of patients initiat-
`ing TNF-a antagonists during 2000–2006 showed that
`virtually all patients had previously taken other drug
`
`categories.15,16 In a private health insurance claims
`database analysis of RA patients initiating TNF-a
`antagonists, NSAIDs, corticosteroids, methotrexate,
`and other synthetic DMARDs had been used by
`49%–60%, 45%–53%, 44%–52%, and 29%–41% of
`patients, respectively,
`in the prior 3 months (the
`ranges depending on the specific TNF-a antagon-
`infliximab, adalimumab).16 And in
`ist—etanercept,
`the CORRONA registry, two thirds (67.8%) of RA
`patients initiating a TNF-a antagonist had previously
`received methotrexate and one third (36.9%) had
`received prednisone.15
`The present longitudinal study shows that the dur-
`ation of
`treatment with other pharmacotherapies
`before initiating biologics decreased sharply during
`the decade 2000–2010. In 2008–2010, RA patients
`spent an average of 2.2 years on NSAIDs/steroids
`and 2.0–2.4 years on synthetic DMARDs before initi-
`ating biologics, values about half the average for the
`decade 2000–2010. The data also suggest that patients
`spent less time on NSAIDs/steroids prior to initiating a
`synthetic DMARD, which is consistent with American
`College of Rheumatology guidelines recommending
`treatment with DMARDs soon after diagnosis.
`Analyses of administrative health claims data sets
`have inherent limitations. Administrative claims data-
`bases do not include the detailed clinical information
`that would explain treatment decisions. Patients in the
`LifeLinkTM Health Plan Claims Database are gener-
`ally demographically representative of the national,
`commercially insured population, but the database
`does not
`include Medicare or Medicaid patients
`(other than Medicare Risk plans) and is not necessarily
`socioeconomically or geographically reflective of the
`US population of RA patients. Furthermore, the diag-
`nosis of RA is often difficult and may take time to fully
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`80
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`Journal of Medical Marketing 13(2)
`
`Figure 4. Treatment time (years) since rheumatoid arthritis (RA) diagnosis until commencing biologic treatment, by
`category of initial treatment, in 2000–2010 (upper panel), 2005–2007 (middle panel), and 2008–2010 (lower panel).
`aPercentages to the right of the bars indicate the proportion of patients with a given treatment flow. Numbers within bars
`are the years of treatment with the indicated drug class. Upper panel, 2000–2010 (N¼ 131,797); middle panel; 2005–2007
`(N¼ 46,440); lower panel, 2008–2010 (N¼ 62,009).
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`Goutsou et al.
`
`81
`
`study has
`confirm. However, a Veterans Affairs
`demonstrated that ICD-9 and pharmacy codes can
`be reliably used to diagnose RA.17
`In conclusion, the use of biologics to treat estab-
`lished RA increased during 2000–2010. Use of bio-
`logics
`as 1st-line
`treatment
`remained relatively
`constant at about 5%, in accord with treatment guide-
`lines, but the durations of treatment with NSAIDs/
`corticosteroids or conventional DMARDs prior to
`starting biologics decreased.
`
`Acknowledgements
`
`The authors thank medical writers Lauren Weisenfluh and
`Alan Morrison, PhD, for assistance in the preparation of this
`manuscript, and Puneet K. Singhal at Merck & Co., Inc. for
`input on research methods and earlier versions of this
`manuscript.
`
`Funding
`
`Study funding was provided by Merck & Co., Inc.
`
`Conflict of interest
`
`The authors declare that they do not have any conflicts of
`interest.
`
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