Abatacept (Orencia^®_, Bristol-Myers Squibb Company, Princeton, NJ) is a selective costimulation modulator which inhibits T cell (T lymphocyte) activation. Activated T lymphocytes are implicated in the development of rheumatoid arthritis (RA) and are found in the synovium of individuals with RA. This document addresses the indications for the use of abatacept.

Note: Please see the following document for information on additional drugs which may be used in the treatment of RA:

• DRUG.00002 Tumor Necrosis Factor Antagonists
• DRUG.00041 Rituximab (Rituxan^®)
• DRUG.00043 Tocilizumab (Actemra^®)

Medically Necessary: 

Abatacept is considered medically necessary for the treatment of moderately to severely active rheumatoid arthritis (RA) when all of the following criteria are met:

• Individual is 18 years of age or older; and
• Is being used to reduce signs and symptoms, induce major clinical response, inhibit the progression of structural damage, and improve physical function; and
• Has had an inadequate response to a trial of one or more non-biologic or biologic disease modifying anti-rheumatic drugs (DMARDs), such as methotrexate (MTX), or a tumor necrosis factor (TNF) antagonist; and
• May be used alone or in combination with non-biologic DMARDs; and
• Is not used in combination with a biologic DMARD (e.g. TNF antagonist).

Abatacept is considered medically necessary for the treatment of moderately to severely active polyarticular juvenile idiopathic arthritis (JIA) when all of the following criteria are met:

• Individual is six years of age or older, and
• Is being used to reduce signs and symptoms of the disease; and
• Has had an inadequate response to a trial of one or more non-biologic or biologic DMARDs, such as MTX, or a TNF antagonist; and
• May be used alone or in combination with MTX; and
• Is not used in combination with a biologic DMARD (e.g. TNF antagonist).

Not Medically Necessary:

Abatacept is considerednot medically necessary for an individual with any of the following:

• Using abatacept in combination with TNF antagonists or other biologic RA therapy, such as anakinra (Kineret^®_,Amgen, Thousand Oaks, CA);
• Tuberculosis or other active serious infections or a history of recurrent infections;  
• Individual has not had a tuberculin skin test (TST) or Centers for Disease Control (CDC)-recommended equivalent to rule out latent tuberculosis.

Investigational and Not Medically Necessary:

Abatacept is considered investigational and not medically necessary for all other indications, including, but not limited to treatment of psoriatic arthritis, scleroderma and systemic lupus erythematosus.

Abatacept was first approved on December 23, 2005 by the U.S. Food and Drug Administration (FDA) for reducing signs and symptoms, inducing major clinical response, slowing the progression of structural damage, and improving physical function in adults with moderately to severely active RA who have had an inadequate response to one or more DMARDs, such as MTX, or a TNF antagonist. Abatacept may be used as monotherapy or concomitantly with DMARDs other than TNF antagonists. Subsequently, the label was updated with the FDA approved indication "for reducing signs and symptoms in pediatric patients six years and older with moderately to severely active polyarticular JIA" and by the removal of the requirement of an inadequate response to one or more DMARDs, such as MTX, or a TNF antagonist in adult RA. However, the majority of clinical trials for abatacept were conducted in individuals (pediatric and adult) who had an inadequate response to one or more DMARDs. There is insufficient published peer reviewed medical literature available to support the use of abatacept as first line therapy.

Adult Rheumatoid Arthritis (RA)

Genovese and colleagues (2005) evaluated the safety and efficacy of abatacept in a randomized, double-blind, phase three trial of adults at least 18 years of age with active RA and an inadequate response to at least three months of a TNF antagonist (also known as anti–TNF alpha therapy). From December 10, 2002 to June 2, 2004, 258 individuals were randomly assigned and treated with abatacept and 133 were randomly assigned and received a placebo. At the time of randomization, subjects had to have increased C-reactive protein levels, at least 10 swollen joints and at least 12 tender joints. They also had to have been taking an oral DMARD or anakinra for at least three months with a stable dose for at least 28 days. Use of oral corticosteroids, but no more than 10 mg of prednisone or its equal per day was allowed if there had been a stable dose for at least 28 days. Dose changes of the background DMARDs were not allowed except to avoid adverse effects. Abatacept or placebo was administered on days 1, 15, and 29 and every 28 days thereafter for 6 months. Anti–TNF alpha therapy was discontinued prior to randomization. The rates of American College of Rheumatology (ACR) 20 responses (indicating a clinical improvement of 20 percent or greater) and improvement in functional disability, as reflected by scores for the Health Assessment Questionnaire (HAQ) disability index, were assessed. After six months, the rates of ACR 20 responses were 50.4 percent in the abatacept group and 19.5 percent in the placebo group (P<0.001); the respective rates of ACR 50 and ACR 70 responses were also significantly higher in the abatacept group than in the placebo group (20.3 percent vs 3.8 percent, P<0.001; and 10.2 percent vs 1.5 percent, P=0.003). At six months, a greater number of subjects in the abatacept group than in the placebo group had a clinically meaningful improvement in physical function, as reflected by an improvement from baseline of at least 0.3 in the HAQ disability index (47.3 percent vs 23.3 percent, P<0.001). The incidence of adverse events and peri-infusional adverse events was 79.5 percent and 5.0 percent, respectively, in the abatacept group and 71.4 percent and 3.0 percent, respectively, in the placebo group. The incidence of serious infections was 2.3 percent in each group. The authors concluded results showed evidence that abatacept is clinically effective and has an acceptable safety profile in those with RA and an inadequate response to anti–TNF alpha therapy.

Kremer and colleagues (2005) in a 12 month, multicenter, randomized, double-blind, placebo-controlled study investigated the safety, efficacy, and immunogenicity of abatacept in individuals with active RA despite treatment with MTX. A total of 339 subjects meeting selection criteria were randomly assigned to receive either 2 mg/kg abatacept (n = 105), 10 mg/kg abatacept (n = 115), or placebo (n = 119). Concomitant therapy of MTX was also administered. Study results reported included that a greater percentage of individuals treated with 10 mg/kg abatacept met the ACR 20% improvement criteria (achieved an ACR20 response) at one year as compared with the percentage who received placebo (62.6% vs 36.1%; P < 0.001). In addition, greater percentages of individuals treated with 10 mg/kg abatacept achieved ACR50 responses (41.7% vs 20.2%; P <0.001) and ACR70 responses (20.9% vs 7.6%; P = 0.003) as compared to those who received a placebo. Adverse events were comparable between the groups and no significant formation of neutralizing antibodies was noted. The authors concluded that abatacept was associated with sustained and significant clinical reduction in disease activity and improvements in physical function.

In a phase III, double-blind, randomized, placebo controlled trial (the AIM study), Kremer and colleagues (2006) studied abatacept in individuals with active RA who had an inadequate response to MTX. Six hundred fifty two adults were randomized in a 2:1 ratio to receive a monthly administration of abatacept at 10mg/kg or placebo, while continuing the background DMARD, most often MTX. Efficacy was assessed with measurements of ACR 20, 50, and 70 which refer to the percentage of improvement (20%, 50%, and 70%, respectively) in tender and swollen joint counts. After 1 year of treatment, ACR 20, 50, and 70 response rates were significantly higher in the abatacept group than the placebo group (80% vs 60%, 53.3 vs 33.8, and 26.7% vs 12% respectively, p<.001). The study also showed that abatacept significantly slowed radiographic progression of joint damage. In 2008, Kremer and colleagues reported on a two year follow-up of this study. Individuals who received placebo during year one were switched to abatacept and those taking abatacept continued with it. The authors noted that those who continued to take abatacept at two years maintained their ACR response rates.

In "the abatacept study of safety in use with other RA therapies (ASSURE trial)", Weinblatt and colleagues (2006) studied the safety of abatacept in individuals who had been receiving traditional nonbiologic or biologic DMARDs. This was a one year, multicenter, randomized, double blind trial in which treatment consisting either of abatacept or placebo was administered on days 1, 15, and 29 and every four weeks after for 14 total doses. All study subjects were required to continue to receive their background RA therapies consisting of biologic DMARDs, non biologic DMARDs, or both. A total of 1,456 subjects were randomized and 1,441 received at least one dose of study medication. The frequency of adverse events in the abatacept and placebo groups were similar; however, when evaluated according to background therapy, serious adverse events occurred more often in the subgroup receiving abatacept with a biologic agent (22.3%) than in the other subgroups (11.7-12.5%). The authors concluded that abatacept in combination with synthetic DMARDs improved physical function and were well tolerated; however, abatacept in combination with biologic background therapies was associated with increased serious adverse events.

Westhovens and colleagues (2006) assessed the safety and efficacy of abatacept in individuals with early RA with poor prognostic factors who had not previously been treated with MTX. In this double blind, phase IIIb study, 509 individuals with RA for two years or less were randomized to receive abatacept plus methotrexate (n=256), or placebo plus methotrexate (n=253) for one year. At one year, a significantly greater number of abatacept plus methotrexate treated subjects achieved disease remission (41.4% vs 23.3%) and the frequency of adverse events was comparable between both groups. The authors concluded that the combination of abatacept plus methotrexate was more effective than methotrexate alone, but noted the study may have been limited by its short term duration of one year.

In an open label extension of the AIM trial, Genant and colleagues (2008) assessed the progression of structural damage after 2 years of abatacept treatment. Five hundred thirty nine individuals were treated with abatacept in the open-label period (378 initially randomized to abatacept and 161 to placebo). A high retention rate was maintained, with 90% of the subjects who entered the extension completing two years. Radiographic assessment of the hands and feet was performed at baseline, one year and two years. Following two years of treatment with abatacept, 50% of subjects had no progression of structural damage, 56% of those treated with abatacept had no progression during the first year compared with 45% of those treated with placebo. In the second year of treatment with abatacept more individuals had no progression than in the first year (66% vs 56%).

Schiff and colleagues (2008) evaluated the safety and efficacy of abatacept or infliximab vs placebo in a multicenter, randomized, double blind, and placebo controlled trial. A total of 431 individuals with RA and an inadequate response to MTX were randomized in a 3:3:2 ratio to abatacept (approximately 10 mg/kg every 4 weeks, n = 156), infliximab (3 mg/kg every 8 weeks, n = 165), or placebo (every 4 weeks, n = 110) by intravenous infusion. At randomization, individuals had active disease despite background MTX. Similar clinical demographics and clinical characteristics were present at baseline between groups. The primary endpoint of the study was to evaluate a reduction in disease activity, measured by Disease Activity Score 28 (based on erythrocyte sedimentation rate levels; DAS28 (ESR) with abatacept versus placebo at six months. Secondary endpoints included reduction in DAS28 (ESR) with infliximab versus placebo at six months. Additional secondary endpoints at six months and one year included a mean reduction in DAS28 (ESR) with abatacept vs infliximab. Study results included a reduction in DAS28 (ESR) at day 197 which was significantly greater with abatacept vs placebo, reduction in DAS28 (ESR) at day 197 was greater in the infliximab vs placebo groups, and also a greater reduction in DAS28 (ESR) at day 365 with abatacept vs infliximab. The authors concluded abatacept and infliximab both offer clinical improvements to those with an inadequate response to MTX; however, abatacept had a relatively more acceptable safety and tolerability profile than the infliximab group.

Schiff and colleagues (2009) reported on "the six month safety and efficacy of abatacept in patients with RA who underwent a washout after anti-tumour necrosis factor therapy or were directly switched to abatacept: ARRIVE trial". In this international open label trial, the safety, tolerability and efficacy of abatacept in RA subjects who had failed anti- TNF therapy and were either switched directly to abatacept or after completing a washout were assessed. A total of 1046 (449 washout, 597 direct switch) with similar baseline characteristics between groups were evaluated. At six months, adverse events and discontinuations due to adverse events were comparable in both groups and there were no opportunistic infections. There were also similar clinically meaningful improvements seen in both groups at six months. The authors conclusions included: "these results demonstrate the acceptable safety and tolerability and clinically meaningful efficacy benefits of abatacept in patients with an inadequate response to anti-TNF therapy, a population representative of those encountered in clinical practice."

The ACR (2008) issued recommendations for the use of nonbiologic and biologic disease-modifying antirheumatic drugs in RA. For each final recommendation, the strength of evidence was assigned using the methods of the American College of Cardiology (i.e. level of evidence A, data were derived from multiple RCTs or meta-analyses). Recommendations issued for abatacept state: "The TFP (Task Force Panel) recommends the use of abatacept in patients for whom methotrexate in combination with DMARDs or sequential administration of other nonbiologic DMARDs led to an inadequate response, and with at least moderate disease activity and features of a poor prognosis (level A evidence for high disease activity)."

Polyarticular Juvenile Idiopathic Arthritis (JIA) 

The FDA approval of abatacept for use in reducing signs and symptoms of moderately to severely active polyarticular juvenile RA in individuals age six years and older was based on a three-part study including an open-label extension in children with polyarticular JIA. Ruperto and colleagues (2008) reported on the study which was conducted at 45 pediatric rheumatology centers in Europe, Latin America, and the USA. One hundred ninety children and adolescents age six to 17 years with moderately to severely active polyarticular JIA who had an inadequate response to one or more DMARDs, such as MTX or TNF antagonists, were enrolled. Criteria for enrollment included at least five active joints (those with swelling or limited range of motion, accompanied by either pain or tenderness) and active disease (at least two active joints and two joints with limited range of motion). All DMARDs, except methotrexate, were withdrawn and not given during the trial. At study entry, 74% of subjects were receiving MTX and remained on a stable dose of MTX. Those not receiving MTX did not initiate MTX treatment. Clinical assessments were completed prior to drug administration at all visits.

In Period A (open-label, lead-in), subjects received 10 mg/kg (maximum 1000 mg per dose) of abatacept intravenously on days one, 15, 29, and monthly thereafter. Response was assessed according to the ACR Pediatric definition of improvement, defined as greater than or equal to 30% improvement in at least three of the six JIA core set variables and greater than or equal to 30% worsening in not more than one of the six JIA core set variables. At the end of Period A, 122 subjects who had improved by 30% according to ACR pediatric definitions were randomized into the double-blind phase (Period B) and received either abatacept or placebo for six months or until disease flare. Disease flare was defined as worsening of 30% or more in at least three of the six JIA core response variables and at least 30% worsening in not more than one of the six variables. Improvement was defined as an improvement of 30% or more in at least three of six ACR core response variables and at least 30% worsening in not more than one variable. Improvements were also defined by 50%, 70%, and 90% improvements in the ACR pediatric criteria. At the conclusion of Period A (at day 113), two-thirds of the 190 enrolled subjects had improved by 30% or more according to ACR pediatric response criteria. Similar proportions of subjects with different disease subtypes improved by 30% or more. During the double-blind randomized withdrawal phase (Period B), abatacept treated subjects experienced significantly fewer disease flares compared to those treated with placebo (20% vs 53%); 95% CI of the difference (15%, 52%). The risk of disease flare among individuals continuing on abatacept was less than one third than that for those withdrawn from abatacept treatment (hazard ratio=0.31, 95% CI [0.16, 0.59]). Among subjects who received abatacept throughout the study (Period A, Period B, and the open-label extension Period C), the proportion of pediatric ACR responders has remained consistent for 1 year (Product Information, 2009).

Ruperto and colleagues (2010a) studied health-related quality of life (HRQOL) in children and adolescents with JIA treated with abatacept in periods A and B of the previously reported on trial. HRQOL assessments performed included a parent-administered 50 item Child Health Questionnaire (CHQ) used to assess physical, social and emotional aspects in children plus physical and psychosocial summary scores, and also parent-administered pain, sleep, and daily activity assessments. A total of 190 subjects from period A and 122 from period B were analyzed. In period A, there were improvements demonstrated across all of the CHQ domains (greatest improvement was in pain and discomfort) with abatacept. At the end of period B, children treated with abatacept had greater improvements versus placebo in all domains (except behavior) and both summary scores. Similar improvement was seen with pain and sleep. For daily activity participation, an additional 2.6 school days per month and 2.3 parents' usual activity days per month were gained in period A responders with abatacept, and additional gains were made in period B (1.9 vs 0.9 [P = 0.033] and 0.2 vs -1.3 [P = 0.109] school days per month and parents' usual activity days per month, respectively, in abatacept- versus placebo-treated subjects). A significant study limitation was that HRQOL assessments were parent or caregiver reported evaluations. The authors concluded that the results of this study demonstrated that abatacept provided significant and meaningful improvements in HRQOL.

Ruperto and colleagues (2010b) described results from the third phase (Period C) of their long-term, open-label double-blind, controlled, randomized withdrawal trial. A total of 153 (90%) of the 170 children completing the open-label lead-in phase (Period A) entered the open-label long term extension (LTE). All children in the LTE phase were treated with 10 mg/kg abatacept administered intravenously every four weeks, with or without methotrexate. Efficacy results were based on data obtained from the 153 participants who entered the open-label LTE phase and reflect greater than or equal to 21 months (589 days) of treatment. By day 589, 90%, 88%, 75%, 57%, and 39% of those treated with abatacept during the double-blind and LTE phases achieved responses according to the ACR Pediatric 30 % (Pedi 30), Pedi 50, Pedi 70, Pedi 90, and Pedi 100 improvement criteria, respectively. Similar response rates were observed by day 589 among those previously treated with a placebo. Among children who had not achieved an ACR Pedi 30 response at the end of the open-label lead-in phase and who advanced directly into the LTE, 73%, 64%, 46%, 18%, and 5% achieved ACR Pedi 30, Pedi 50, Pedi 70, Pedi 90, and Pedi 100 responses, respectively, by day 589 of the LTE. The authors concluded that the results of this study suggest that abatacept is a promising treatment of JIA in children and adolescents.

In 2011, the ACR issued recommendations for the treatment of JIA which included initiation of abatacept as a treatment approach in certain individuals with history of JIA of five or more joints who have previously received a TNF antagonist inhibitor for four months or who have received more than one TNF antagonist inhibitor sequentially. Abatacept was also recommended for certain individuals with JIA who have received methotrexate and a TNF antagonist inhibitor.

Other Proposed Uses 

There has been some interest in the use of abatacept for individuals with scleroderma (Ong 2010), systemic lupus erythematosus (Merrill 2010) and psoriatic arthritis (Mease 2011). Published evidence regarding the use of abatacept for these conditions is limited and further investigation in large randomized controlled clinical trials is needed.

RA is a chronic inflammatory and progressive disease characterized by symmetrical joint involvement, which causes pain, swelling, stiffness, and loss of function in the joints. If left untreated it may lead to joint destruction and progressive disability. The disease affects over two million Americans usually striking people between the ages of 20 and 60, and people in their mid to late fifties are especially vulnerable. RA is three times more common in women than in men.

JIA (formerly known as juvenile RA) is a form of RA in children that generally occurs prior to the age of 16, favors one or more large joints and can interfere with normal bone growth. It is the most common chronic pediatric rheumatic disease.

Polyarticular JIA is a form of JIA affecting five or more joints. It often affects the same joints on both sides of the body (symmetrical arthritis). Girls are more frequently affected by polyarticular JIA than boys. In teenagers, it often resembles RA.

Typical treatment of adult RA and JIA includes treatment with DMARDs, such as methotrexate. However, not all individuals respond to such treatments. Clinical studies support the safety and efficacy of abatacept for the treatment of RA and polyarticular JIA in certain individuals who have had an inadequate response to one or more DMARDs.

The following are important limitations of use from the Product Information Label (2009):

• Abatacept should not be administered concomitantly with TNF antagonists.
• Abatacept is not recommended for use concomitantly with other biologic RA therapy, such as anakinra.

 The following are warnings and precautions from the Product Information Label (2009): 

• Concomitant use with a TNF antagonist can increase the risk of infections and serious infections
• Hypersensitivity, anaphylaxis, and anaphylactoid reactions
• Individuals with a history of recurrent infections or underlying conditions predisposing to infections may experience more infections
• Discontinue if a serious infection develops
• Screen for latent TB infection prior to initiating therapy. Those testing positive should be treated prior to initiating abatacept
• Live vaccines should not be given concurrently or within 3 months of discontinuation
• Individuals with juvenile idiopathic arthritis should be brought up to date with all immunizations prior to abatacept therapy
• Based on its mechanism of action, abatacept may blunt the effectiveness of some immunizations
• Individuals with COPD may develop more frequent respiratory adverse events

Biologic DMARDs: A class of drugs thought to work by targeting components of the immune system by blocking specific immune cytokines, blocking other cytokines, binding with cytokines suppressing Il-12 and IL-23, or by directly suppressing lymphocytes; includes the anti-CD20 monoclonal antibodies (e.g. rituximab), interleukin-1 receptor antagonists (IL-1Ra) (e.g. anakinra), interleukin-6 (IL-6) receptor antagonists (e.g. tocilizumab), interleukin-(IL)-12 and IL-23 antagonists (e.g. ustekinumab), selective co-stimulation modulators (e.g. abatacept), and the tumor necrosis factor (TNF) antagonists (inhibitors).

Disease modifying anti-rheumatic drugs (DMARDs): A variety of medications which work by altering the immune system function to halt the underlying processes that cause certain forms of inflammatory arthritis including RA, ankylosing spondylitis, and psoriatic arthritis.

Interferon gamma (IFN- γ) release assay (IGRA): A test that aids in detecting Mycobacterium tuberculosis infection, both latent infection and infection manifesting as active tuberculosis that may be used for surveillance purposes and to identify persons likely to benefit from treatment. FDA-approved IGRAs include the 1) QuantiFERON-TB Gold test (GFT-G), 2) QuantiFERON-TB Gold In-Tube test (QFT-GIT), and the 3) T-SPOT.TB test (T-Spot).

Nonbiologic DMARDs: A class of drugs, also referred to as synthetic DMARDs, thought to work by altering the immune system function to halt the underlying processes that cause certain forms of inflammatory conditions, although their exact mechanisms of action are unknown. Drugs in this class include azathioprine, hydroxychloroquine, leflunomide, methotrexate (MTX), minocycline, organic gold compounds, penicillamine, and sulfasalazine.

Psoriatic arthritis: A form of arthritis that can affect any joint within the body, either in a single joint or in the same joint on both sides of the body.

Scleroderma: A systemic disorder of connective tissue characterized by induration and thickening of the skin, abnormalities of the blood vessels, and fibrotic degenerative changes in various body organs

Systemic lupus erythematosus: A chronic multi-system autoimmune disease which can range from mild, single organ disease to severe, multiple-organ disease, which can lead to organ failure.

Tumor Necrosis Factor (TNF) antagonists: A class of biologic DMARDs designed to neutralize inflammatory cytokines that target specific pathways of the immune system and either enhance or inhibit immune response. Drugs in this class include adalimumab (Humira^®_, Abbott Laboratories, North Chicago, IL), certolizumab pegol (Cimzia^®_, UCB, Inc., Smyrna, GA), etanercept (Enbrel^®_, Immunex Corporation, Thousand Oaks, CA), golimumab (Simponi^™_, Centocor Ortho Biotech Inc., Horsham, PA), and infliximab (Remicade^®_, Centocor Ortho Biotech Inc., Horsham, PA).

The following codes for treatments and procedures applicable to this document are included below for informational purposes.  Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy.  Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member. 

When services may be Medically Necessary when criteria are met:

When services are Not Medically Necessary:
For the procedure and diagnosis codes listed above in those instances described in the Position Statement as not medically necessary

When services are Investigational and Not Medically Necessary:
For the procedure and diagnosis codes listed above when criteria are not met, and for all other diagnoses not listed.

Future ICD-10 coding (effective 10/01/2013)
A draft of ICD-10 Coding related to this document, as it might look today, is available for reference and comments at: Appendix 1: Future ICD-10 coding

Peer Reviewed Publications: 

1. Genant HK, Peterfy CG, Westhovens R, et al. Abatacept inhibits progression of structural damage in rheumatoid arthritis: results from the long-term extension of the AIM trial. Ann Rheum Dis. 2008; 67(8):1084-1089.
2. Genovese MC, Becker JC, Schiff M, et al. Abatacept for rheumatoid arthritis refractory to tumor necrosis factor alpha inhibition. N Engl J Med. 2005; 353(11):1114-1123.
3. Hampton T. Trials reveal promising options for treating juvenile rheumatoid arthritis. JAMA. 2008; 299(1):27-28.
4. Kremer JM, Dougados M, Emery P, et al. Treatment of rheumatoid arthritis with the selective costimulation modulator abatacept: twelve-month results of a phase iib, double-blind, randomized, placebo-controlled trial. Arthritis Rheum. 2005; 52(8):2263-2271.
5. Kremer JM, Genant HK, Moreland LW, et al. Effects of abatacept in patients with methotrexate-resistant active rheumatoid arthritis: a randomized trial. Ann Intern Med. 2006; 144(12):865-876.
6. Kremer JM, Genant HK, Moreland LW, et al. Results of a two-year follow up study of patients with rheumatoid arthritis who received a combination of abatacept and methotrexate. Arthritis Rheum. 2008; 58(4):953-963.
7. Lutt JR, Deodhar A. Rheumatoid arthritis: strategies in the management of patients showing an inadequate response to TNF alpha antagonists. Drugs. 2008; 68(5):591-606.
8. Massarotti EM. Clinical and patient-reported outcomes in clinical trials of abatacept in the treatment of rheumatoid arthritis. Clin Ther. 2008; 30(3):429-442.
9. Mease P, Genovese MC, Gladstein G, et al. Abatacept in the treatment of patients with psoriatic arthritis: Results of a six-month, multicenter, randomized, double-blind, placebo-controlled, phase II trial. Arthritis Rheum. 2011; 63(4):939-948.
10. Merrill JT, Burgos-Vargas R, Westhovens R, et al. The efficacy and safety of abatacept in patients with non-life-threatening manifestations of systemic lupus erythematosus: results of a twelve-month, multicenter, exploratory, phase IIb, randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2010; 62(10):3077-3087.
11. Ong VH, Denton CP. Innovative therapies for systemic sclerosis. Curr Opin Rheumatol. 2010; 22(3):264-272.
12. Rindfleisch JA, Muller D. Diagnosis and management of rheumatoid arthritis. Am Fam Physician. 2005; 72(6):1037-1047.
13. Ruperto N, Lovell DJ, Li T, Paediatric Rheumatology International Trials Organisation (PRINTO); Pediatric Rheumatology Collaborative Study Group (PRCSG). Abatacept improves health-related quality of life, pain, sleep quality, and daily participation in subjects with juvenile idiopathic arthritis. Arthritis Care Res (Hoboken). 2010a; 62(11):1542-1551.
14. Ruperto N, Lovell DJ, Quartier P, et al. Paediatric Rheumatology International Trials Organization; Pediatric Rheumatology Collaborative Study Group. Abatacept in children with juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled withdrawal trial. Lancet. 2008; 372(9636):383-391.
15. Ruperto N, Lovell DJ, Quartier P, et al; Paediatric Rheumatology International Trials Organization; Pediatric Rheumatology Collaborative Study Group. Long-term safety and efficacy of abatacept in children with juvenile idiopathic arthritis. Arthritis Rheum. 2010b; 62(6):1792-1802.
16. Schiff M, Keiserman M, Codding C, et al. Efficacy and safety of abatacept or infliximab vs placebo in ATTEST: a phase III, multi-centre, randomised, double-blind, placebo-controlled study in patients with rheumatoid arthritis and an inadequate response to methotrexate. Ann Rheum Dis. 2008; 67(8):1096-1103.
17. Schiff M, Pritchard C, Huffstutter JE, et al. The 6-month safety and efficacy of abatacept in patients with rheumatoid arthritis who underwent a washout after anti-tumour necrosis factor therapy or were directly switched to abatacept: the ARRIVE trial. Ann Rheum Dis. 2009; 68(11):1708-1714.
18. Weinblatt M, Combe B, Covucci A, et al. Safety of the selective costimulation modulator abatacept in rheumatoid arthritis patients receiving background biologic and nonbiologic disease-modifying antirheumatic drugs: A one-year randomized, placebo-controlled study. Arthritis Rheum. 2006; 54(9):2807-2816.
19. Westhovens R, Robles M, Ximenes AC, et al. Clinical efficacy and safety of abatacept in methotrexate-naive patients with early rheumatoid arthritis and poor prognostic factors. Ann Rheum Dis. 2009; 68(12):1870-1877.

Government Agency, Medical Society, and Other Authoritative Publications:

1. Abatacept (systemic). In: DrugPoints^® System [Internet database]. Greenwood Village, CO: Thomson Healthcare. Last modified March 18, 2011. Available at: http://www.thomsonhc.com. Accessed on March 30, 2011.
2. American College of Rheumatology Subcommittee on Rheumatoid Arthritis Guidelines. Guidelines for the management of rheumatoid arthritis: 2002 Update. Arthritis Rheum. 2002; 46(2):328-346.
3. American Hospital Formulary Service^® (AHFS). AHFS Drug Information 2011^®_. Bethesda, MD: American Society of Health-System Pharmacists^®_, 2011.
4. Beukelman T, Patkar NM, Saag KG, et al. 2011 American College of Rheumatology recommendations for the treatment of juvenile idiopathic arthritis: Initiation and safety monitoring of therapeutic agents for the treatment of arthritis and systemic features. Arthritis Care Res (Hoboken). 2011; 63(4):465-482.
5. Bristol-Myers Squibb, BMS-188667 in Children and Adolescents with Juvenile Rheumatoid Arthritis. NLM Identifier: NCT00095173. Last updated on August 3, 2010. Available at: http://www.clinicaltrials.gov/ct2/show/NCT00095173?term=NCT00095173&rank=1. Accessed on March30, 2011.
6. Centers for Disease Control (CDC) and Prevention. Updated guidelines for using interferon gamma release assays to detect Mycobacterium tuberculosis infection - United States, 2010; 59(No. RR 5):1-28. Available at: http://www.cdc.gov/mmwr/pdf/rr/rr5905.pdf. Accessed on March 30, 2011
7. Orencia [Product Information], Princeton, NJ. Bristol-Myers Squibb; August 2009. Available at: http://packageinserts.bms.com/pi/pi_orencia.pdf. Accessed on March 30, 2011.
8. Saag KG, Teng GG, Patkar NM. American College of Rheumatology. American College of Rheumatology 2008 recommendations for the use of nonbiologic and biologic disease-modifying antirheumatic drugs in rheumatoid arthritis. Arthritis Rheum. 2008; 59(6):762-784.

Orencia
PolyarticularJuvenile Idiopathic Arthritis (JIA)
Rheumatoid Arthritis

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