Description:
Simponi is a recombinant human monoclonal antibody specific for human tumor necrosis factor alpha (TNFα). Simponi neutralizes the biological activity of TNFα and inhibits binding of TNFα with its receptors. TNF, a naturally occurring cytokine, mediates inflammation and modulates cellular immune responses. Increased levels of TNF are found in the synovial fluid of patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). TNF has an important role in both the pathologic inflammation and the joint destruction that are characteristic of these diseases. 

Simponi is indicated for the following uses:

• Treatment of adults with moderately to severely active RA in combination with methotrexate (MTX)
• Treatment of adults with active PsA either alone or in combination with MTX or other non-biologic disease modifying antirheumatic drugs (DMARDs)
• Treatment of adults with active AS either alone or in combination with MTX or other non-biologic DMARDs
• Inducing and maintaining clinical response, improving endoscopic appearance of the mucosa during induction, inducing clinical remission, and achieving and sustaining clinical remission in induction responders in adults with moderate-to-severe ulcerative colitis (UC) who have demonstrated corticosteroid dependence or who have had an inadequate response to or failed to tolerate oral aminosalicylates, oral corticosteroids, azathioprine or 6-mercaptopurine

Policy:
Rheumatoid Arthritis
The use of Golimumab (Simponi) may be considered MEDICALLY NECESSARY for the treatment of rheumatoid arthritis when the following criteria is met:

• Patient is 18 years of age or older; and
• Patient has moderately to severely active rheumatoid arthritis; and
• Golimumab (Simponi) is used in combination with methotrexate unless there is a contraindication to taking methotrexate or a history of methotrexate intolerance; and
• Patient has failed treatment to one or more disease-modifying anti-rheumatic drugs (DMARDs); and 

Psoriatic Arthritis
The use of Golimumab (Simponi) for the treatment of Psoriatic Arthritis may be considered MEDICALLY NECESSARY when the following criteria is met:. 

• Patient is 18 years of age or older
• Patient has active psoriatic arthritis
• Golimumab (Simponi) is used alone or in combination with methotrexate
• Patient has failed treatment to one or more disease-modifying anti-rheumatic drugs (DMARDs)

Ankylosing Spondylitis
The use of Golimumab (Simponi) may be considered MEDICALLY NECESSARY when the following criteria is met: 

• Patient is 18 years of age or older.
• Patient has active ankylosing spondylitis.
• Patient has failed treatment with at least two nonsteroidal anti-inflammatory drugs (NSAIDs) or has documented contraindications to non steroidal anti-inflammatory drug usage

Ulcerative Colitis
The use of Golimumab (Simponi) may be considered MEDICALLY NECESSARY when the following criteria is met:

• Patient is 6 years of age or older; and
• Patient has moderately to severely active ulcerative colitis; and
• Patient has demonstrated corticosteroid dependence OR has failed treatment with oral aminosalicylates, oral corticosteroids, azathioprine, or 6-mercaptopurine; and

Polyarticular Juvenile Idiopathic Arthritis (PJIA)
The use of Golimumab (Simponi) may be considered MEDICALLY NECESSARY when the following criteria is met:

• Patient is 18 years of age or older
• Patient has moderate to severe PJIA
• Prescribed by or in consultation with a rheumatologist
• Trial and failure, contraindication, or intolerance to one of the following non-biologic disease-modifying antirheumatic drugs (DMARDS): Arava (leflunomide), methotrexate (Rheumatrex/Trexall)

Note: The FDA approved prescribing information recommends: 

• Simponi should not be prescribed with other biologic products approved to treat rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, or ulcerative colitis (including, but not limited to tumor necrosis factor blockers, anakinra, and abatacept). 

Use of Golimumab (Simponi) for indications other than those listed above is considered investigational/unproven therefore is considered NOT MEDICALLY NECESSARY. 

Use of Golimumab (Simponi) if the criteria for the indications listed above are not met is considered NOT MEDICALLY NECESSARY.

NOTE: Please see CAM 149 Simponi ARIA for intravenous indications and uses.

Rationale:
Simponi is a tumor necrosis factor (TNF) blocker approved for the treatment of rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), and ulcerative colitis (UC). Tumor necrosis factor is a naturally occurring cytokine that is involved with the inflammatory and immune responses. Excessive activation of immune effector cells and overproduction of TNF can cause severe inflammation and tissue damage. Inhibition of TNF activity in certain inflammatory diseases may alleviate symptoms and prevent disease progression. 

Simponi is a human IgG1қ monoclonal antibody specific for human tumor necrosis factor-α (TNF- α) that binds to both the soluble and transmembrane bioactive forms of human TNF-α. This interaction prevents the binding of TNF-α to its receptors, thereby inhibiting the biological activity of TNF-α (a cytokine protein). Elevated TNF-α levels in the blood, synovium and joints have been implicated in the pathophysiology of several chronic inflammatory diseases such as RA, PsA and AS. TNF-α is an important mediator of the articular inflammation that is characteristic of these diseases. 

Simponi is the first anti-TNF agent administered subcutaneously (SC) and dosed once a month for the treatment of RA, PsA and AS and has a loading period for UC followed by a monthly dose. The Simponi drug product is a sterile solution of the golimumab antibody supplied as either a single dose prefilled syringe (with a passive needle safety guard) or a single dose prefilled autoinjector. Simponi does not contain preservatives. The solution is clear to slightly opalescent, colorless to light yellow with a pH of approximately 5.5. Simponi is provided in one strength: 

• 50mg of the golimumab antibody in 0.5 mL of solution. Each 0.5mL of Simponi contains 50 mg of the golimumab antibody, 0.44 mg of L-histidine and L-histidine monohydrochloride monohydrate, 20.5 mg of sorbitol, 0.08 mg of polysorbate 80 and Water for Injection. 

Disease-Modifying Anti-Rheumatic Drugs (DMARDS)
Disease-modifying anti-rheumatic drugs are used as a second line defense for the treatment of RA, AS, PsA and lupus. These drugs slow the disease process by modifying the immune system: 

• Methotrexate
• Cyclosporine
• Sulfasalazine
• Mercaptopurine
• Gold Compounds 

For patients with RA, Simponi should be given in combination with methotrexate (MTX) and for patients with PsA or AS, Simponi may be given with or without MTX or other non-biologic DMARDs. For patients with RA, PsA, UC or AS, corticosteroids, non-biologic DMARDs, and/or non steroidal anti-inflammatory drugs (NSAIDs) may be continued during treatment with Simponi. 

Rheumatoid Arthritis
Simponi, in combination with MTX, has been shown to improve RA signs and symptoms according to the American College of Rheumatology (ACR) responses, including tender and swollen joint count, pain, physician and patient global assessment scores, as well as disability index (HAQ-DI), and acute markers of inflammation, compared to MTX alone. Simponi + MTX efficacy in these parameters has been observed in MTX-naïve, MTX inadequate responders and patients previously treated with ≥ anti-TNF agent. Simponi dosing for RA is 50mg subQ once per month 

Psoriatic Arthritis
Available data from a Phase III clinical trial (GO-REVEAL) including patients with active PsA who had an inadequate response to NSAIDS or DMARDS suggests that Simponi provides dramatic improvement in both arthritis and psoriasis symptoms. Substantial efficacy of Simponi in patients with PsA has been observed using a dose of 50 mg once monthly, with or without concomitant MTX, significantly reduced clinical signs and symptoms of PsA. 

Ankylosing Spondylitis 
Available data from a Phase III clinical trial (GO-RAISE) including adult patients with active AS despite current or previous NSAID or DMARD therapy suggests that Simponi provides dramatic improvement in spondylitis symptoms, including total back pain and morning stiffness as well as improvement in patient’s global assessment of disease activity and physical function according to the BASFI. Substantial efficacy of Simponi in patients with AS has been observed using a dose of 50mg once monthly. Results of this study indicate that Simponi significantly reduced clinical signs and symptoms of AS. Simponi dosing for AS is 50mg subQ once per month. 

Ulcerative Colitis
Available date from Phase III trials (UC-1 and UC-2) in adult patients with moderately to severely active ulcerative colitis show that a greater proportion of patients achieved clinical response, clinical remission and had improvement of endoscopic appearance of the mucosa. Simponi dosing for UC is 200mg subq at week 0, followed by 100mg at week 2, and then 100mg every 4 weeks. 

FDA or Other Governmental Regulatory Approval
U.S. Food and Drug Administration (FDA) 

Simponi is a TNF blocker indicated for the treatment of adult patients with: 

• Moderately to severely active RA, in combination with MTX.
• Active PsA, alone or in combination with MTX.
• Active AS.
• Moderately to severely active ulcerative colitis. 

WARNING RISK OF SERIOUS INFECTIONS
Patients treated with Simponi are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. 

Simponi should be discontinued if a patient develops a serious infection. 

Reported infections include: 

• Active tuberculosis, including reactivation of latent tuberculosis. Patients with tuberculosis have frequently presented with disseminated or extrapulmonary disease. Patients should be tested for latent tuberculosis before Simponi use and during therapy. Treatment for latent infection should be initiated prior to Simponi use.
• Invasive fungal infections, including histoplasmosis, coccidioidomycosis, and pneumocystosis. Patients with histoplasmosis or other invasive fungal infections may present with disseminated, rather than localized, disease. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. Empiric antifungal therapy should be considered in patients at risk for invasive fungal infections who develop severe systemic illness.
• Bacterial, viral, and other infections due to opportunistic pathogens. 

The risks and benefits of treatment with Simponi should be carefully considered prior to initiating therapy in patients with chronic or recurrent infection.

Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with Simponi, including the possible development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy.

References:

1. Food and Drug Administration .Labeling of the Drug Simponi www.fda.gov
2. FDA Simponi Formulary Dossier
3. Oldfield V, Plosker GL. Golimumab: in the treatment of rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. BioDrugs. 2009; 23(2):125-35.
4. Kavanaugh A, McInnes I, Mease P, Krueger GG, Gladman D, Gomez-Reino J, Papp K, Zrubek J, Mudivarthy S, Mack M, Visvanathan S, Beutler A. Golimumab, a new human tumor necrosis factor alpha antibody, administered every four weeks as a subcutaneous injection in psoriatic arthritis: Twenty-four-week efficacy and safety results of a randomized, placebo-controlled study. Arthritis Rheum. 2009 Apr; 60(4):976-86.
5. Keystone EC, Genovese MC, Klareskog L, Hsia EC, Hall ST, Miranda PC, Pazdur J, Bae SC, Palmer W, Zrubek J, Wiekowski M, Visvanathan S, Wu Z, Rahman MU; GO-FORWARD Study. Golimumab, a human antibody to tumour sic necrosis factor {alpha} given by monthly subcutaneous injections, in active rheumatoid arthritis despite methotrexate therapy: the GO-FORWARD Study. Ann Rheum Dis. 2009 Jun; 68(6):789-96. Epub 2008 Dec 9.
6. Inman RD, Davis JC Jr, Heijde D, Diekman L, Sieper J, Kim SI, Mack M, Han J, Visvanathan S, Xu Z, Hsu B, Beutler A, Braun J. Arthritis Rheum. Efficacy and safety of golimumab in patients with ankylosing spondylitis: results of a randomized, double-blind, placebo-controlled, phase III trial. 2008 Nov; 58(11):3402-12.
7. Hutas G. Golimumab, a fully human monoclonal antibody against TNF alpha. Curr Opin Mol Ther. 2008 Aug; 10(4):393-406.
8. Zhou H, Jang H, Fleischmann RM, Bouman-Thio E, Xu Z, Marini JC, Pendley C, Jiao Q, Shankar G, Marciniak SJ, Cohen SB, Rahman MU, Baker D, Mascelli MA, Davis HM, Everitt DE. Pharmacokinetics and safety of golimumab, a fully human anti-TNF-alpha monoclonal antibody, in subjects with rheumatoid arthritis. J Clin Pharmacol. 2007 Mar; 47(3):383-96.

Coding Section

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, Blue Cross Blue Shield Association technology assessment program (TEC) and other nonaffiliated technology evaluation centers, reference to federal regulations, other plan medical policies and accredited national guidelines.

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