Blue Cross of Idaho Logo

Express Sign-on

Thank you for registering with Blue Cross of Idaho

If you are an Individual or Family Member under age 65, please register here.

If you are an Medicare or Medicare Supplement member, please register here.

New Options for Affordable Health Insurance
MP 5.01.99 Treatment of Arthropathies with Biologic-Response Modifiers

Medical Policy
Section
Prescription Drugs
 
Original Policy Date
03/18/2008
Last Review Status/Date
Revised Local Policy/4:2011
Issue
4:2011
Return to Medical Policy Index

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.


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); and the spondyloarthropathy, ankylosing spondylitis (AS).

Rheumatoid Arthritis (RA)

RA is a chronic, progressive, inflammatory autoimmune disease affecting about 1% of the US adult population and occurs approximately 2 to 3 times or more frequently in women than men  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 (messenger proteins), including tumor necrosis factor-alpha (TNF-a). 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 popluation

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 and may be as high as 6 per 100,000. Men and women are equally affected. There is similarity in the histopathogenesis of PsA and RA, including the role of cytokines such as tumor necrosis factor alpha (TNF-a), 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, dactlytitis, 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

JIA refers to a number of different conditions, all of which affect children, and all of which have immune-mediated joint inflammation as their major manifestation.  The prevalence is estimated at 13.9 per 100,000 per year.  Males are affected approximately 1.5 times more than females.

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 20-40% of patients with PsA may have some degree of sacroiliitis 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.

As of the date of this policy the following biologic-response moderators have FDA marketing approvals as specified.

Table 1. U.S. Food and Drug Administration (FDA) Marketing Approvals for the Biologic-Response Modifiers [3-10]

Drug

Rheumatoid
Arthritis

Psoriatic
Arthritis

Ankylosing
Spondylitis

Juvenile
Idiopathic
Arthritis

Etanercept (Enbrel®)

√*

√*

adalimumab (Humira®)

√*

√*

certolizumab pegol (Cimzia®)

 

 

 

golimumab (Simponi®)

 

anakinra (Kineret®)

 

 

 

infliximab (Remicade®)

 

abatacept (Orencia®)

 

 

rituximab (Rituxan®)

 

 

 

Tocilizumab (Actemra®)

 

 

√ (ages 2 and up)

 

*pediatric indication

Drug monitoring recommendations include[16, 30-33]:

  • Evaluation for the development of signs and symptoms of infection during and after treatment 
  • Signs and symptoms of anaphylaxis, anaphylactoid reaction, and hypersensitivity reactions (hypotension, urticaria, and dyspnea) 
  • Signs and symptoms of new or worsening heart failure 
  • Signs and symptoms of malignancy 
  • For infliximab (Remicade®), abatacept (Orencia®), certolizumab pegol (Cimzia®), golimumab (Simponi®), and etanercept (Enbrel®), patients should be evaluated for latent tuberculosis prior to therapy and periodically during therapy and checked for evidence of prior Hepatitis B virus infection in those with Hepatitis B risk factors before initiating therapy.
  • During anakinra (Kineret®) therapy, it is recommended to get a neutrophil count prior to initiating therapy, monthly for the first 3 months of therapy, and after 6, 9, and 12 months.

The American College of Rheumatology16 has recommended

  • Generally, for mild-to-moderate rheumatoid arthritis, oral nonbiologic DMARDs prior to biologic DMARDs.
  • Tumor-necrosis-factor-α (TNF-α) inhibitors such as etanercept (Enbrel®), adalimumab (Humira®), and infliximab (Remicade®) for longer duration and more severe disease that is unresponsive to nonbiologic DMARDs or when the nonbiologic DMARDs are not tolerated.
  • Abatacept (Orencia®) 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.
  • Rituximab (Rituxan) in patients for whom methotrexate in combination with DMARDs or sequential administration of other nonbiologic DMARDs led to an inadequate response, with high disease activity and features of a poor prognosis.


Policy

Identified Biologic-Response Modifiers for Specific Conditions/Uses

Rheumatologic Condition/Use

Biologic-Response Modifier

Rheumatoid Arthritis

adalimumab (Humira®)

infliximab (Remicade®) plus methotrexate

etanercept (Enbrel®)

certolizumab pegol (Cimzia®)

golimumab (Simponi®) plus methotrexate
abatacept (Orencia®)

anakinra (Kineret®)
rituximab (Rituxan®)
Tocilizumab (Actemra®)

Juvenile Idiopathic Arthritis

etanercept (Enbrel®)

adalimumab (Humira®)
abatacept (Orencia®) plus methotrexate

Tocilizumab (Actemra®)

Ankylosing Spondylitis

adalimumab (Humira®)

infliximab (Remicade®)

etanercept (Enbrel®)
golimumab (Simponi®)

Psoriatic Arthritis

adalimumab (Humira®)

etanercept (Enbrel®)

golimumab (Simponi®)
infliximab (Remicade®)

 

For each specific condition/use and specific biologic-response modifiers listed in each category, there are no studies indicating that any of the medication is more effective than any other in the treatment of inflammatory arthropathies with the following exceptions:

  • Indirect evidence exists that anakinra may be less effective than other agents in rheumatoid arthritis
  • Only poor quality evidence supports the use of rituximab in the treatment of rheumatoid arthritis.

Since there is no evidence of greater effectiveness of one biologic as compared to any others, products with the lowest cost may be considered preferred as most cost-effective.

  • Inclusion of multiple treatment options is recommended: 
    • Individual responses and tolerability to biologic-response modifiers are unpredictable and may vary between patients. Products also vary in their mechanism of action. 
    • Because responses vary, if one of the biologic DMARDs provides an inadequate response, another biologic medication may be effective. 
  • Combination therapy: 
    • In rheumatoid arthritis, the best response is seen when methotrexate is used concomitantly with any of the biologics. Infliximab and golimumab have been shown to be effective only when used with methotrexate. 
    • There is no evidence that concomitant administration of multiple biologic medications is safe or more effective than when administered alone. 
  • Dosing considerations: 
    • There are no reliable clinical data to suggest that doses or frequencies exceeding those recommended in each product’s prescribing information are safe or more effective than recommended doses. 
    • The efficacy of doses of adalimumab higher than 40 mg every other week in rheumatologic conditions (including rheumatoid arthritis) has not been proven to be more effective than 40 mg every other week. The benefit of increasing the dose of adalimumab from 40 mg every other week to 40 mg weekly as monotherapy is uncertain. 

-  Although one study reported a modest improvement in ACR50, it did not find a significant difference in ACR20 or ACR70. [29] 
-  Importantly, the study was not designed to evaluate the comparative effectiveness of higher doses, so the comparison between    weekly and every other week adalimumab, done through post hoc analysis, is exploratory.
-  Significant rates of subjects failed to complete the clinical trial, ranging from 26% to 56% per treatment arm, eroding confidence in the results. [29]

 

 

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
    • For rheumatoid arthritis or juvenile idiopathic arthritis: Prior treatment with methotrexate is ineffective after at least a 6- to 12-week treatment course.
      • Quantity limitations:
      • For rheumatologic conditions adalimumab may be utilized in quantities of 40 mg every 2 weeks. 
      • The evidence does not support use of adalimumab in maintenance doses exceeding 40 mg every 2 weeks. 

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).

  • For rheumatoid arthritis
    • Prior treatment with methotrexate is ineffective …
    • Infliximab must be administered with an oral DMARD (such as methotrexate). 
    • Consideration may be given to using infliximab without a concomitant oral DMARD when etanercept, adalimumab, and abatacept each have been ineffective, contraindicated, or not tolerated, as these medications have been proven to be effective when given without the concomitant administration of an oral DMARD. 
  • Quantity limitations: Up to 6 infusions in a 6-month period. 
    • The maximum number of infusions that may be utilized per year is based on the diagnosis being treated.
    • Rheumatoid arthritis, a maximum of 12 infusions in a 1-year period, based on a recommended infusion interval of up to every 4 to 8 weeks. 
    • Ankylosing spondylitis, a maximum of 9 infusions in a 1-year period, based on a recommended infusion interval of every 6 weeks. 
    • Psoriatic arthritis, a maximum of 7 infusions in a 1-year period, based on a recommended infusion interval of every 8 weeks. 

Etanercept (Enbrel®) 

  • For rheumatoid arthritis or juvenile idiopathic arthritis: Prior treatment with methotrexate is ineffective after at least a 6- to 12-week treatment course.
  • Quantity limitations: The evidence does not support use of etanercept at a dose greater than 50 mg per week for rheumatologic conditions.

Anakinra (Kineret®) 

  • For rheumatoid arthritis: Prior treatment with methotrexate is ineffective after at least a 6- to 12-week treatment course.
  • Quantity limitations: Anakinra may be utilized in quantities of 28 syringes (1 syringe dispensing pack) every 4 weeks up to 100 mg of anakinra subcutaneously once daily. 

 

Certolizumab pegol (Cimzia®)

  • For rheumatoid arthritis: Prior treatment with methotrexate is ineffective after at least a 6- to 12-week treatment course
  • Quantity limitations: 
    • Initially, certolizumab pegol may be utilized in quantities up to 10 of the 200 mg vials in the first 12 weeks.
    • Certolizumab pegol may be utilized in quantities of 2 of the 200 mg vials or syringes each month.

Golimumab (Simponi®)

  • For rheumatoid arthritis:
    • Prior treatment with methotrexate is ineffective after at least a 6- to 12-week treatment course.
    • Golimumab is administered with an oral DMARD (such as methotrexate).
    • Consideration may be given to using golimumab without a concomitant oral DMARD when etanercept, adalimumab, and abatacept each have been ineffective, contraindicated, or not tolerated, as these medications have been proven to be effective when given without the concomitant administration of an oral DMARD. 
  • Quantity limitations: Golimumab may be utilized in quantities of 50 mg per month. 

Tocilizumab (Actemra®)Tocilizumab (Actemra®) may be considered medically necessary for rheumatoid arthritis (RA) who have had an inadequate response to treatment with tumor necrosis factor (TNF)-inhibitors and for the treatment of systemic juvenile idiopathic arthritis for patients ages 2 years and older

  • The adult recommended starting dosage for rheumatoid arthritis is 4mg/Kg every 4 weeks followed by an increase to 8mg/Kg based upon clinical response. Infusions of greater than 800 mg are not recommended. 
  • The recommended dosage for systemic juvenile idiopathic arthritis for patients less than 30 kg weight is 12 mg/kg and for patients at or above 30 kg weight 8 mg/kg.

Abatacept (Orencia®)
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.

Orencia® may be considered medically necessary for the arthropathy indication of combination therapy with MTX in moderate to severe active rheumatoid arthritis (RA) or juvenile idiopathic arthritis when prior treatment with MTX is ineffective after at least a 6-12 week treatment course.

Initially, Orencia®, may be utilized in quantities up to 8 infusions in a 6-month period.

The maximum number of infusions that may be utilized per year is 13 infusions.

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 erythematosus is considered investigational.

Rituximab (Rituxan®) may be considered medically necessary arthropathy indication of combination therapy with MTX in moderate to severe active rheumatoid arthritis (RA) when prior treatment with MTX is ineffective after at least a 6-12 week treatment course, and there was inadequate response with one or more tumor-necrosis-factor (TNF) antagonist therapies.

Rituximab 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.


Policy Guidelines

Retreatment with infliximab may be approved based on the following criteria:

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

  • 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-a 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.

Recommended 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 not sooner than every six months. Authorizations will be limited to 4 infusions (2 courses) per year.

Psoriatic Arthritis

Etanercept (Enbrel®)

Enbrel®, self administered by subcutaneous injection, is a preferred TNF-a antagonist product for this indication; prescribers are encouraged to consider initial TNF-a antagonist therapy with etanercept after careful consideration of potential risks and benefits for the patient. Coverage for PsA may be approved at 50mg once weekly.

Adalimumab (Humira®)

Humira® is also a preferred TNF-a antagonist product for the treatment of patients with PsA. Prescribers are encouraged to consider initial TNF-a 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)

Etanercept (Enbrel®)

Enbrel®, self-administered by subcutaneous injection, is the preferred TNF-a antagonist product for this indication, prescribers are encouraged to consider initial TNF-a 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-a antagonist product for the treatment of patients with ankylosing spondylitis. Coverage of adalimumab may be approved in patients with spondylarthropathy after 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®)

Spondyloarthropathy patients may be approved for therapy with Remicade®, if they have have failed treatment with Enbrel® 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 5 mg/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 must be submitted with every prior authorization, so that treatment efficacy can be evaluated. 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.

Other Arthropathies

The medical necessity of etanercept (Enbrel®), infliximab (Remicade®), adalimumab (Humira®), abatacept (Orencia®), or rituximab (Rituxan®) for use in patients with other arthropathies is considered investigational. However, those patients refractory to treatment with recognized conventional therapies may be considered on a case-by-case basis.


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

Policy History

03/18/08 Policy added to Prescription Drug section New Policy
10/06/09 Policy updated with new drug only Added Ustekinumab (Stelara®) to policy 
08/20/10 Replace policy (remains local) policy guidelines revised; policy statement unchanged. Stelara removed
4/18/11 local policy updated JIA indication added to Actemra

Search for Policies

Policy Feedback