MP 5.01.99

Treatment of Arthropathies with Targeted Immune Modulators

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Medical Policy
Section Prescription Drugs	Original Policy Date 03/18/2008	Last Review Status/Date Created as Local Policy/3:2008
Issue 3:2008		Return to Medical Policy Index

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Disclaimer

Our medical policies are designed for informational purposes only and are not an authorization, or an explanation of benefits, or a contract.  Receipt of benefits is subject to satisfaction of all terms and conditions of the coverage.  Medical technology is constantly changing, and we reserve the right to review and update our policies periodically.

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Description

Arthropathies are a group of heterogeneous connective tissue disorders affecting the joints, which  share certain common features such as inflammation and altered patterns of immune regulation. Those conditions at focus in this policy include rheumatoid arthritis (RA); psoriatic arthritis (PsA); ankylosing spondylitis (AS), and juvenile idiopathic arthritis (JIA).

Rheumatoid Arthritis (RA)
RA is a chronic, progressive, inflammatory autoimmune disease affecting about 1% of the US adult population and occurs aproximately 3 times or more frequently in women than men (ACR Subcommittee on Rheumatoid Arthritis Guidelines, 2002). Almost 80% of RA cases occur in patients between 35 and 50 years of age (Kavanaugh and Lipsky, 1996); usually a time of peak social productivity. The underlying cause of RA is unknown, but the disease is characterized by persistent inflammation of the synovium, cartilage loss, and bone erosion in peripheral joints, usually in a symmetric fashion. This inflammation is believed to be mediated by both B- and T- cells and a variety of cytokines (messanger proteins), including tumor necrosis factor-alpha (TNF-alpha). Research has shown that joint damage occurs within the first two years of symptoms and diagnosis, and progresses rapidly if not treated. Although RA primarily affects the joints, it is a systemic disease and does cause systemic and extra-articular clinical features (e.g., fever, fatigue, anorexia, weight loss and anemia). Patients with RA also have greater mortality than the general population.

Psoriatic Arthritis (PsA)
PsA is characterized as a spondyloarthropathy associated with psoriasis. The true incidence is unknown, and is variably reported to occur in 6-24% of patients with psoriasis, which equates to about 1-3% of the general population. There is similarity in the histopathogenesis of PsA an RA, including the role of cytokines such as tumor necrosis factor alpha (TNF-alpha), with some exceptions. Several subsets of PsA have also been described. PsA is characterized by morning stiffness, neck pain and stiffness, back pain and stiffness, inflamed joints, deformities, daclytitis, sacroiliac stress pain and distal interphalangeal joint disease. The course of PsA is variable, but about 20% of patients may develop a chronic progressive form of the disease that results in severe joint destruction.

Juvenile Idiopathic Arthritis

Juvenile idiopathic arthritis is a triad of rheumatoid diseases that begins at or before age 16. Signs may include arthritis, fever, rash, adenopathy, splenomegaly and iridocyclitis. The etiology is unknown, but there seems to be a genetic predisposition and an autoimmune pathophysiology.

The initial sumptoms and signs of JIA tend to fall into three possible patterns:

• Systemic onset (Still's disease) occurs in about 20% of patients.  High fever, rash, splenomegaly, generalized adenopathy, and serositis with pericarditis or pleuritis are common. These may precede the development of arthritis. Fever (quotidian) is often highest in the afternoon or evening and may persist for up to two weeks. A typical transient rash often appears with the fever or may be diffuse and migratory, with urticarial or macular lesions.
• Pauciarticular onset is characterized by involvement of ≤ four joints. It occurs in about 40% of patients, usually young girls. Iridocyclitis is most common in pauciartiulcar JIA, developing in nearly 20%. Many affected older boys have the HLA-B27 allele. Most of these boyts subsequently develop classic features of one of the spondyloarthropathies (eg, ankylosing spondylitis, psoriatic arthritis, reactive arthritis).
• Polyarticular onset involves ≥ five joints, often ≥ 20. It occurs in the remaining 40% of patients and is often similar to adult RA. Arthritis tends to be symmetric and develop slowly.

Complete remissions occur in 50 to 75% of treated patients. Patients with polyarticular onset and a positive RF have a less favorable prognosis.

Other Spondyloarthropathies (SpAs)

The spondyloarthropathies are a heterogeneous set of disorders characterized by axial skeletal involvement and frequent association with the HLA-B27 antigen. Ankylosing spondylitis (AS) is probably the most familiar spondyloarthropathy, which is characterized not by the inflammation of synovium, as seen in RA, but inflammation of the enthesis, the site where ligaments, tendons and joint capsules insert into bone. Inflammation around the vertebrae, facet joints, and feet can lead to fibrosis, ossification, deformity and ankylosis. Variations in incidence among different racial groups support the hypothesis of a genetic role in AS. In the United States, AS is believed to affect approximately 1-3 persons/1000, or about 350,000 to 1 million individuals.

While peripheral arthritis is commonly seen in association with psoriasis, approximately 20-4-% of patients with PsA may have some degree of sacroilitis with paravertebral ossification. The skin manifestations associated with the arthropathy are not necessarily widespread and may be localized.

About 20% of patients with inflammatory bowel disease may have evidence of sacroiliitis and some 20% of these patients may progress to actual ankylosing spondylitis. The course of the spondylitis does not correlate with the bowel activity.

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Policy

Enbrel® and Humira®

Etanercept (Enbrel®) and Adalimumab (Humira®) are the preferred anti-TNF antagonist products and may be considered medically necessary for the following FDA-approved arthropathy indications, either in combination with methotrexate (MTX) or alone:

• moderate to severe rheumatoid arthritis;
• moderate to severe polyarticular juvenile idiopathic arthritis;
• psoriatic arthritis; and
• ankylosing spondylitis

See Policy Guideline section of this policy for criteria.

Infliximab (Remicade®)

Infliximab (Remicade®) may be considered medically necessary for its FDA-approved arthropathy indication of combination therapy with MTX in moderate to severe active rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS).

Abatacept (Orencia®)

Abatacept (Orencia®) a costimulation modulator, may be considered medically necessary for its FDA-approved indication for treatment of moderately to severely active rheumatoid arthritis (RA) and idiopathic juvenile polyarticular arthritis (JIA) in children 6 years of age and older.

Abatacept (Orencia®) is considered investigational for the treatment of PsA, due to a current lack of adequate published clinical trial evidence for the agent in patients with this condition.

See Policy Guideline section of this policy for criteria.

Rituximab (Rituxan®)

Rituximab (Rituxan®), a chimeric monoclonal antibody targeted at CD20 antigen expressed on B-cells, may be considered medically necessary for its FDA-approved indication for the treatment of moderately to severely active rheumatoid arthritis (RA). Use of Rituximab (Rituxan®) to treat lupus erythematosis is considered investigational.

Rituximab (Rituxan®) is considered investigational for the treatment of PsA, due to a current lack of adequate published clinical trial evidence for the agent in patients with this condition.

Anakinra (Kineret®) 

Anakinra (Kineret®) is an interleukin-1 (IL-1) and Interleukin-1 Receptor Antagonist (IL-1Ra) and may be considered medically necessary for the reduction in signs and symptoms and slowing the progression of structural damage in moderately to severely active rheumatoid arthritis, in patients 18 years of age or older who have failed one or more disease-modifying anti-rheumatic drugs (DMARDs). Kineret®  can be used alone or in combination with DMARDs other than tumor necrosis factor (TNF) blocking agents.

Certulizamab pegol (Cimzia®) 

Certulizamab pegol (Cimzia®) is a tumor necrosis factor (TNF) blocker and may be considered medically necessary for the treatment of adults with moderate to severely active rheumatoid arthritis who have failed conservative therapy with one or more disease-modifying anti-rheumatic drugs (DMARDs).

See Policy Guideline section of this policy for criteria.

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Policy Guidelines

Rheumatoid Arthritis and Juvenile Idiopathic Arthritis

Evidence from randomized controlled trials show that the combination of a TNF blocker and methotrexate yield better results for RA than monotherapy with respect to excellent clinical responses (ACR 70, remission, and radiological outcomes).  Improvement should be apparent in 12-24 weeks of therapy.

Etanercept (Enbrel®)

Raising the dose of etanercept does not seem to have an added benefit in 12 or 24 week studies.

Infliximab (Remicade®)

Retreatment with infliximab administered in conjunction with methotrexate may be approved at a maximum of 6 infusions in a 12 month time period following lack of significant response to one of the self injected TNF blockers based on the following criteria:

An improvement in any one of the following American College of Rheumatology assessment components:

• painful joint count
• swollen joint count
• patient pain assessment
• patient global assessment
• physician global assessment
• patient self-assessed disability
• acute phase reactants (ESR or CRP)

Retreatment should be terminated if the patient develops symptoms of antibody reaction, such as myalgias, rash, fever and polyarthralgia, which have been reported to occur 2 or more years after the initial infusion in patients who continue to receive retreatment.

For patients with an incomplete response, adjusting the dosing frequency to as often as every 4 weeks or increasing the dose to a maximum of 10 mg/kg, but not both concurrently, may be approved.
Patients not responding to TNF-alpha antagonist therapy after 14 weeks are unlikely to respond, and consideration should be given to discontinuing infliximab therapy.

Abatacept (Orencia®)

Coverage of Orencia® may be be approved for the treatment of patients with moderately to severely active RA who have failed one or more preferred TNF antagonist products (Enbrel® or Humira®), or for whom the use of these preferred agents would not be clinically appropriate.

Recommend dosing for Orencia® is weight-based and should not exceed 1000mg per dose. Therapy is initiated with 3 infusions administered 2 weeks apart, followed by 1 infusion every 4 weeks.

Concurrent use of a TNF antagonist or anakinra with Orencia® is not recommended because efficacy was not substantially enhanced and a higher incidence of infections and serious infections were reported in patients receiving a TNF antagonist in combination with abatacept compared with those receiving a TNF antagonist alone in clinical trials.

Rituximab(Rituxan®)

Coverage of Rituxan with MTX may be approved for the treatment of patients with moderately to severely active RA who have failed one or more preferred TNF antagonist products (Enbrel® or Humira®), or for whom the use of these preferred agents would not be clinically appropriate.

Doses should not exceed 1000 mg, and a recommended treatment course consists of 2 infusions administered 2 weeks apart. Authorizations will be limited to 4 infusions (2 courses) per year. Exceptions to this limitation may be considered on a case-by-case basis.

Psoriatic Arthritis

Clinical improvement should be expected within 12 weeks of treatment.

Etanercept (Enbrel®)

Enbrel®, self administered by subcutaneous injection, is a preferred TNF-alpha antagonist product for this indication; prescribers are encouraged to consider initial TNF-alpha antagonist therapy with etanercept after careful consideration of potential risks and benefits for the patient.

Adalimumab (Humira®)

Humira® is also a preferred TNF-alpha antagonist product for the treatment of patients with PsA. Prescribers are encouraged to consider initial TNF-alpha antagonist therapy with Humira® after careful consideration of potential risks and benefits for the patient.

Coverage for PsA may be approved at doses of 40 mg every other week.

Infliximab (Remicade®)

Remicade® therapy studied for this condition consists of a three-infusion course of 5 mg/kg over a 6-week timeframe (weeks 0, 2 and 6), followed by a single infusion every 8 weeks as maintenance. Coverage of Remicade® may be approved in patients with psoriatic arthritis who have failed Enbrel® or Humira®, or for whom the use of these agents would not be clinically appropriate.

Other Spondyloarthropathies (SpAs)

There is no current evidence that dosage increases in TNF blockers are more effective in the treatment of AS.

Etanercept (Enbrel®)

Enbrel®, self-administered by subcutaneous injection, is the preferred TNF-alpha antagonist product for this indication, prescribers are encouraged to consider initial TNF-alpha antagonist therapy with etanercept after careful consideration for potential risks and benefits for the patient. Doses exceeding 50 mg/week may be required in spondylarthropathy patients.

Adalimumab (Humira®)

Humira® is also a preferred TNF-alpha antagonist product for the treatment of patients with ankylosing spondylitis. Coverage of adalimumab may be approved in patients with spondylarthropathy after careful consideration of the potential risks and benefits for the patient. Coverage for spondylarthropathies may be approved at doses of 40 mg every other week.

Infliximab (Remicade®)

SpAs patients may be approved for therapy with Remicade®, if they have failed treatment with Enbrel® or Humira® or they are not clinically appropriate candidates for either agent, and have failed at least 3 standard therapies, such as:

• nonsteroidal anti-inflammatory drugs (NSAIDS);
• immunomodulatory agents (e.g., methotrexate, azathioprine, mercaptopurine, cyclosporine);
• local steroid injections; or
• sulfasalazine

Initial therapy studied in these conditions consists of three-infusion course at 5mg/kg over a 6-week timeframe (weeks 0, 2 and 6). Coverage of retreatment (single 5 mg/kg doses every 6 weeks) will require documentation of maintenance or improvement in disease severity before the first retreatment, and every 12 months thereafter.

Baseline disease severity indices should be submitted so that treatment efficacy can be evaluated after the initial course. Such indices may include tender and swollen joint counts, patient global assessment, physician global assessment, patient pain assessment, levels of acute phase reactants (e.g., ESR, CRP), BASDAI score, or ASAS response.

Abatacept (Orencia®)

Orencia® is considered investigational for the treatment of other spondylarthropathies including AS, due to a lack of adequate published clinical trial evidence for the agent in patients with this condition.

Rituximab (Rituxan®)

Rituxan® is considered investigational for the treatment of other spondylarthropathies including AS, due to a lack of adequate published clinical trial evidence for the agent in patients with this condition.

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Codes

Codes	Number	Description
CPT	90760	Intravenous infusion, hydration; initial, up to 1 hour
	90761	each additional hour, up to 8 hours (list separately in addition to code for primary procedure)
	90765	Intravenous infusion, for therapy, prophylaxis, or diagnosis (specify substance or drug); initial up to 1 hour
	90766	each additional hour, up to 8 hours (list separately in addition to code for primary procedure)
	96413	Chemotherapy administration, intravenous infusion technique; up to 1 hour, single or initial substance/drug
	96415	Chemotherapy administration, intravenous infusion technique; each additional hour, 1 to 8 hours (list separately in addition to code for primary procedure)
	99070	Supplies and materials Note: Medicare, many Medicaid programs, and some private payers do not accept claims for CPT code 99070.
ICD-9 Procedure	99.29	Injection or infusion of other therapeutic or prophylactic substance
HCPCS	C9249	Injection, certolizumab pegol, 1 mg
	J7050	Infusion, normal saline solution, 250 mg.
	J0129	Abatacept injection (Orencia) for rheumatoid arthritis
	J0135	Injection, Adalimumab (Humira), 20mg
	J1438	Injection, Etanercept (Enbrel), 25 mg
	J1745	Injection, infliximab (Remicade), 10mg
	J3590	Unclassified biologics
	J9310	Rituximab, 100mg
ICD-9 diagnosis	714.0	Rheumatoid arthritis
	714.2	Other RA with visceral or systemic involvement
	714.30	Polyarticular juvenile rheumatoid arthritis, chronic or unspecified
	720.0	Ankylosing Spondylitis
	696.0	Psoriasis, Arthriti/Arthropathic

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Policy History

03/18/08

Policy added to Prescription Drug section

New Policy

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