abatacept (Orencia)
Subject: abatacept for intravenous injection (Orencia®)
Date revised: 12/02/2009
Description
Abatacept inhibits T lymphocyte activation. Activated T lymphocytes are implicated in the pathogenesis of rheumatoid arthritis. Abatacept is approved by the Food and Drug Administration (FDA) for the following indications.
Rheumatoid arthritis (RA).
Polyarticular juvenile idiopathic arthritis (JIA).
Abatacept is available as a preservative-free lyophilized powder in single-use vials containing 250 mg. Each vial must be reconstituted with 10 mL of sterile water for injection using a silicone-free disposable syringe. After reconstitution in the vial, the concentration of abatacept is 25 mg/mL (250 mg/10 mL). The dose is diluted to 100 mL in a bag or bottle and is infused intravenously (IV) over a period of 30 minutes. It must be administered using a low protein binding filter with pore size 0.2 to 1.2 micrometers.
Indications, Medically Necessary
1. RA in adults: Indicated for the treatment of moderate to severe active RA in patients who meet all of the following criteria.
· Abatacept is prescribed by a rheumatologist, and
· Patient has had an inadequate response to at least 2 months of therapy with one of the following non-biologic DMARDs: methotrexate, hydroxychloroquine, leflunomide (Arava®), or sulfasalazine, and
Exceptions to having tried a non-biologic DMARD for 2 months can be made if the patient could not tolerate the non-biologic DMARDs or if there are contraindications to all four of these agents.
· Patient has tried a TNF antagonist, adalimumab (Humira), certolizumab pegol (Cimzia), etanercept (Enbrel), golimumab (Simponi) or infliximab (Remicade) and had an inadequate response after at least 2 months of therapy or was intolerant to one of these TNF antagonists.
For patients who are continuing with abatacept there must be documentation that the patient is or is not on another DMARD in conjunction with abatacept and the other drug therapies that have been used to treat RA.
Dosing in RA in adults: An initial weight-based dose is followed by additional similar doses at 2 and 4 weeks after the first infusion, then every 4 weeks thereafter. See table 1. The maximum dose is 1000 mg. Some clinical trials used 10 mg/kg dosing, but the dosing in table 1 is recommended.
Table 1. Dose of Abatacept in Adults with RA.
Patient’s Body Weight / Dose / Number of 250 mg Vials< 60 kg / 500 mg / 2
60 to 100 kg / 750 mg / 3
> 100 kg / 1000 mg / 4
Initial approval/extended approval: Initial approval is for 3 months (5 doses). This is for the initial dose, doses at weeks 2 and 4, and then doses at week 8 and 12. Patients are evaluated for response after the fifth dose. After 3 months (5 doses), approve for an additional 12 months of therapy if the patient has responded (e.g., less joint pain, morning stiffness, or fatigue; improved function or activities of daily living; decreased soft tissue swelling in joints or tendon sheaths; improved laboratory values; reduced dosage of corticosteroids), as determined by the prescribing rheumatologist. The patient may not have a full response after 5 doses, but there should be some response. Approval for continued therapy is not recommended in patients who have no response by week 16.
Duration of therapy in RA: indefinite in patients who are responding.
Labs/Diagnostics required: Patient should be screened for latent tuberculosis (TB) infection prior to starting therapy and then every year while on abatacept. Screening may include any one of the following: history, tuberculin skin testing, interferon gamma release assay (IGRA), chest x-ray. In general, patients with latent TB infection should begin preventive therapy before starting abatacept.
Waste management: For adults with RA the dose is 500 mg (2 vials) for those weighing < 60 kg; 750 mg (3 vials) for 60 to 100 kg; and 1000 mg (4 vials) for > 100 kg. This dose is given initially and then at weeks 2 and 4 and then every 4 weeks.
Exclusions:
· Concomitant use with anakinra (Kineret); a TNF antagonist (such as etanercept, adalimumab, golimumab, certolizumab pegol, infliximab; or rituximab (Rituxan). When a TNF antagonist is stopped, abatacept can be given at the time when the next dose of a TNF antagonist agent would normally have been given.
· Significant active infection.
· Plaque psoriasis unless the patient also has rheumatoid arthritis.
· Psoriatic arthritis
· Ankylosing spondylitis
· Crohn’s disease
· Ulcerative colitis
· Reactive arthritis
· Systemic lupus erythematosus (SLE).
2. JIA, polyarticular course (regardless of type of onset) in patients 6 years of age and older. Indicated for the treatment of moderate to severe active polyarticular course JIA in patients who meet all of the following criteria.
· Abatacept is prescribed by a rheumatologist, and
· Patient has had an inadequate response to at least 2 months of therapy with one of the following non-biologic DMARDs: methotrexate, hydroxychloroquine, leflunomide, or sulfasalazine, and
Exceptions to trying a non-biologic DMARD for 2 months of therapy can be made if the patient could not tolerate the non-biologic DMARDs or if there are contraindications to all four of these agents.
· Patient has tried adalimumab (Humira), etanercept (Enbrel) or infliximab (Remicade) and had an inadequate response after at least 2 months of therapy or was intolerant to one of these TNF antagonists.
Note: infliximab is not FDA approved in the treatment of JIA, but it has been used extensively for this indication.
Dosing in JIA: In patients aged 6 to 17 years who weigh less than 75 kg, an initial dose of 10 mg/kg is followed by additional similar doses at 2 and 4 weeks after the first infusion, and then every 4 weeks thereafter. The dose should be calculated at each administration. Pediatric patients who weigh 75 kg or greater should follow the adult RA dosing regimen. See table 1. The maximum dose is 1000 mg. JIA may continue into adulthood.
Initial approval/extended approval: Initial approval is for 3 months (5 doses). This is for the initial dose, doses at weeks 2 and 4, and then doses at week 8 and 12. Patients are evaluated for response after the fifth dose. After 3 months (5 doses), approve for an additional 12 months of therapy if the patient has responded (e.g., has improvement in limitation of motion; less joint pain or tenderness; improved function or activities of daily living; decreased duration of morning stiffness or fatigue; reduced dosage of corticosteroids; decreased soft tissue swelling in joints or tendon sheaths; improved laboratory values), as determined by the prescribing rheumatologist. The patient may not have a full response by 3 months, but there should be some response.
Duration of therapy in JIA: indefinite in patients who are responding.
Labs/Diagnostics required: Patient should be screened for latent tuberculosis (TB) infection prior to starting therapy and then every year while on abatacept. Screening may include any of the following: history, tuberculin skin testing, interferon gamma release assay (IGRA), chest x-ray. In general, patients with latent TB infection should begin preventive therapy before starting abatacept.
Waste management: The initial dose in patients aged 6 to 17 years who weigh less than 75 kg is an initial dose of 10 mg/kg is followed by additional similar doses at 2 and 4 weeks after the first infusion, then every 4 weeks thereafter. The dose should be calculated at each administration. Pediatric patients who weigh 75 kg or greater should follow the adult RA dosing regimen. See table 1 for adult dosing. The maximum dose is 1000 mg (4 vials).
Table 2. Dose of Abatacept in Children with JIA.
Patient’s Body Weight / Number of 250 mg Vials≤ 25 kg / 1
> 25 to ≤ 50 kg / 2
> 50 to < 75 kg / 3
≥ 75 kg to 100 kg / 3
> 100 kg / 4
Exclusions:
· Concomitant use with anakinra (Kineret), a TNF antagonist (such as etanercept, adalimumab, golimumab, certolizumab pegol, infliximab), rituximab (Rituxan), or natalizumab (Tysabri). When a TNF antagonist is stopped, abatacept can be given at the time when the next dose of a TNF antagonist agent would normally have been given.
· Significant active infection.
· Plaque psoriasis, unless the patient also has JIA.
· Psoriatic arthritis
· Ankylosing spondylitis
· Crohn’s disease, unless the patient also has JIA.
· Ulcerative colitis
· Reactive arthritis
· Systemic lupus erythematosus (SLE).
References
1. Orencia for injection [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; August 2009.
Rheumatoid arthritis
2. 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;52:2263-2271.
3. Kremer JM, Westhovens R, Leon M, et al. Treatment of rheumatoid arthritis by selective inhibition of T-cell activation with fusion protein CTLA4Ig. N Engl J Med. 2003;349:1907-1915.
4. 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;144:865-876.
5. Genovese MC, Becker JC, Schiff M, et al. Abatacept for rheumatoid arthritis refractory to tumor necrosis factor alpha inhibition. N Engl J Med. 2005;353:1114-1123.
6. Genovese MC, Schiff M, Luggen M, et al. Efficacy and safety of the selective co-stimulation modulator abatacept following 2 years of treatment in patients with rheumatoid arthritis and an inadequate response to anti-TNF therapy. Ann Rheum Dis. 2008;67:547-554.
7. Kremer JM, Genant HK, Moreland LW, et al. Results of a two-year followup study of patients with rheumatoid arthritis who received a combination of abatacept and methotrexate. Arthritis Rheum. 2008;58:953-963.
8. Kremer J, Westhovens R, Luggen M, et al. Long-term efficacy and safety of abatacept through 3 years of treatment in rheumatoid arthritis patients in AIM and ATTAIN trials [abstract 699]. Arthritis Rheum. 2007;56(suppl):S300.
9. Westhovens R, Kremer JM, Moreland LW, et al. Safety and efficacy of the selective costimulation modulator abatacept in patients with rheumatoid arthritis receiving background methotrexate: A 5-year extended phase IIB study. J Rheumatol. 2009;36:736-742.
10. 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;67:1084-1089.
11. Russell AS, Wallenstein GV, Li T, et al. Abatacept improves both the physical and mental health of patients with rheumatoid arthritis who have inadequate response to methotrexate treatment. Ann Rheum Dis. 2007;66:189-194.
12. Westhovens R, Cole JC, Li T, et al. Improved health-related quality of life for rheumatoid arthritis patients treated with abatacept who have inadequate response to anti-TNF therapy in a double-blind, placebo-controlled, multicentre randomized clinical trial. Rheumatology (Oxford). 2006;45:1238-1246.
13. Schiff MH, 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-TNF therapy or were directly switched to abatacept: the ARRIVE trial. Ann Rheum Dis. 2009;68:1708-1714.
14. 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;68:1870-1877.
15. 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;67:1096-1103.
16. Weinblatt M, Schiff M, Goldman A, et al. Selective costimulation modulation using abatacept in patients with active rheumatoid arthritis while receiving etanercept: a randomised clinical trial. Ann Rheum Dis. 2007;66:228-234.
17. 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;54:2807-2816.
· Furst DE, Keystone EC, Kirkham B, et al. Updated consensus statement on biological agents for the treatment of rheumatic diseases, 2008. Ann Rheum Dis. 2008;67 Suppl 3:iii2-25.
· Saag KG, Teng GG, Patkar NM, et al; 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;59:762-784. Available at: http://www.rheumatology.org/publications/guidelines/recommendations.asp?aud=mem Accessed 11/16/2009.
· American College of Rheumatology Subcommittee on Rheumatoid Arthritis Guidelines. Guidelines for the management of rheumatoid arthritis. Arthritis Rheum. 2002;46:328-346. Available at http://www.rheumatology.org/publications/guidelines/raguidelines02.asp?aud=mem. Accessed on 11/16/2009.
· Maxwell L, Singh JA. Abatacept for rheumatoid arthritis. Cochrane Database Syst Rev. 2009 Oct 7;(4):CD007277
Juvenile idiopathic arthritis
18. 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;372:383-391.
Abbreviations
DMARD = disease modifying antirheumatic drug Kg = kilograms
FDA = Food and Drug Administration mL = milliliter
IGRA = interferon gamma release assay RA = rheumatoid arthritis
IV = intravenous TNF = tumor necrosis factor
JIA = juvenile idiopathic arthritis
Overview
Abatacept is a recombinant fully human fusion protein that selectively inhibits T lymphocyte activation by competitively binding to CD80 and CD86, thereby blocking interaction with CD28.1 This provides a co-stimulation signal that is necessary for full activation of T lymphocytes. Activated T lymphocytes are implicated in the pathogenesis of rheumatoid arthritis (RA).
Abatacept is Food and Drug Administration (FDA)-approved for the following indications:1
· reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in adult patients with moderately to severely active RA. Abatacept may be used as monotherapy or concomitantly with traditional disease modifying antirheumatic drugs (DMARDs).
· for reducing signs and symptoms in pediatric patients ≥ 6 years of age with moderately to severely active polyarticular juvenile idiopathic arthritis (JIA). Abatacept may be used alone or in combination with methotrexate.
12/02/2009
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