THIS MEDICAL COVERAGE GUIDELINE IS NOT AN AUTHORIZATION, CERTIFICATION, EXPLANATION OF BENEFITS, OR A GUARANTEE OF PAYMENT, NOR DOES IT SUBSTITUTE FOR OR CONSTITUTE MEDICAL ADVICE. ALL MEDICAL DECISIONS ARE SOLELY THE RESPONSIBILITY OF THE PATIENT AND PHYSICIAN. BENEFITS ARE DETERMINED BY THE GROUP CONTRACT, MEMBER BENEFIT BOOKLET, AND/OR INDIVIDUAL SUBSCRIBER CERTIFICATE IN EFFECT AT THE TIME SERVICES WERE RENDERED. THIS MEDICAL COVERAGE GUIDELINE APPLIES TO ALL LINES OF BUSINESS UNLESS OTHERWISE NOTED IN THE PROGRAM EXCEPTIONS SECTION.
|Dosage/ Administration||Position Statement||Billing/Coding||Reimbursement||Program Exceptions||Definitions|
Humira® (adalimumab) is a recombinant human IgG1 monoclonal antibody specific for human tumor necrosis factor (TNF). Humira® was created using phage display technology resulting in an antibody with human derived heavy and light chain variable regions and human IgF1:k constant regions. Adalimumab is produced by recombinant DNA technology in a mammalian cell expression system and is purified by a process that includes specific viral inactivation and removal steps. It consists of 1330 amino acids and has a molecular weight of approximately 148 kilodaltons.
Adalimumab binds specifically to TNF-alpha and blocks its interaction with the p55 and p75 cell surfact TNF receptors. Adalimumab also lyses surface TNF expressing cells in vitro in the presence of complement. Adalimumab does not bind or inactivate lymphotoxin (TNF-beta). TNF is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. Elevated levels of TNF are found in the synovial fluid of rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis patients and play an in important role in both the pathologic inflammation and the joint destruction that are hallmarks of these diseases. Increased levels of TNF are also found in psoriasis plaques. In plaque psoriasis, treatment with Humira® may reduce the epidermal thickness and infiltration of inflammatory cells. The relationship between these pharmacodynamic activities and the mechanism by which adalimumab exerts its clinical effects is unknown.
Adalimumab also modulates biological responses that are induced or regulated by TNF, including changes in the levels of adhesion molecules responsible for leukocyte mitration.
NOTE: The attached Certificate of Medical Necessity should be completed and submitted with the request for adalimumab, in order to facilitate medical review. To access the certificate of medical necessity, click on the link below, complete the required fields, and print
Adalimumab (Humira®) meets the definition of medical necessity when administered for the following indications (SEE TABLE 1 FOR SPECIFIC CRITERIA):
- Rheumatoid Arthritis
- Juvenile Idiopathic Arthritis
- Psoriatic Arthritis
- Ankylosing Spondylitis
- Crohn’s Disease
- Plaque Psoriasis.
|SPECIFIC CRITERIA FOR HUMIRA® (ADALIMUMAB) THERAPY|
|1. Rheumatoid Arthritis||
|2. Juvenile Idiopathic Arthritis||
|3. Psoriatic Arthritis||
|4. Ankylosing Spondylitis||
|5. Crohn’s Disease||
|6. Plaque Psoriasis||
NOTE: concomitant use of adalimumab and anakinra is NOTrecommended since serious infections have been seen in clinical studies with concurrent use of anakinra and another TNF-blocking agent with no added benefit.
NOTE: Safety and efficacy of adalimumab in pediatric patients for uses other than juvenile arthritis have not been established.
Adalimumab is considered experimental or investigationalfor all other indications since safety and effectiveness have not been established.
THIS INFORMATION IS PROVIDED FOR INFORMATIONAL PURPOSES ONLY AND SHOULD NOT BE USED AS A SOURCE FOR MAKING PRESCRIBING OR OTHER MEDICAL DETERMINATIONS. PROVIDERS SHOULD REFER TO THE MANUFACTURER’S FULL PRESCRIBING INFORMATION FOR DOSAGE GUIDELINES AND OTHER INFORMATION RELATED TO THIS MEDICATION BEFORE MAKING ANY CLINICAL DECISIONS REGARDING IT’S USAGE.
The recommended dose of adalimumab for adult patients with rheumatoid arthritis is 40 mg administered every other week as a subcutaneous injection. Methotrexate, glucocorticoids, salicylates, nonsteroidal anti-inflammatory drugs (NSAIDs), analgesics OR other DMARDsmay be continued during treatment with adalimumab. The dose of adalimumab can be increased to 40 mg per week if methotrexate is not used concomitantly.
Juvenile Idiopathic Arthritis
The recommended dose of adalimumab for patients weighing between 15 kg (33 lbs) to <30 kg (66 lbs) is 20 mg every other week and those weighing >30 kg (66 lbs) the dose is 40mg every other week.
The recommended dose of adalimumab for adult patients with psoriatic arthritis is 40 mg subcutaneously every other week alone or in combination with other disease-modifying anti-rheumaticdrugs.
The recommended dose of adalimumab for adult patients with ankylosing spondylitis is 40 mg subcutaneously every other week alone or in combination with NSAIDS, glucocorticoids, methotrexate or other DMARDs.
The recommended dose of adalimumab for adult patients with Crohn’s disease is 160 mg initially at week 0, 80 mg at week 2, followed by a maintenance dose of 40 mg every other week beginning at week 4. Initial dose may be given as 4 injections on 1 day, or divided over 2 days.
The recommended dose of adalimumab for adult patients with plaque psoriasis is 80 mg initial dose, followed by 40 mg every other week starting one week after initial dose.
Patients treated with adalimumab 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. HUMIRA should be discontinued if a patient develops a serious infection or sepsis. Reported infections include:
The risks and benefits of treatment with adalimumab 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 HUMIRA, including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy.
Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers, of which adalimumab is a member.
Hepatitis B virus reactivation: Use of TNF blockers, including adalimumab, may increase the risk of reactivation of HBV in patients who are chronic carriers of this virus. In some instances, HBV reactivation occurring in conjunction with TNF-blocker therapy has been fatal. The majority of these reports have occurred in patients concomitantly receiving other medications that suppress the immune system, which also may contribute to HBV reactivation. Evaluate patients at risk for HBV infection for prior evidence of HBV infection before initiating TNF-blocker therapy. Exercise caution in prescribing TNF blockers for patients identified as carriers of HBV. Adequate data are not available on the safety or efficacy of treating patients who are carriers of HBV with antiviral therapy in conjunction with TNF-blocker therapy to prevent HBV reactivation. Closely monitor patients who are carriers of HBV and require treatment with TNF blockers for clinical and laboratory signs of active HBV infections throughout therapy and for several months following termination of therapy. In patients who develop HBV reactivation, stop adalimumab and initiate effective antiviral therapy with appropriate supportive treatment. The safety of resuming TNF-blocker therapy after HBV reactivation is controlled is not known. Therefore, exercise caution when considering resumption of adalimumab therapy in this situation and monitor patients closely.
Neurologic effects: Use of TNF-blocking agents, including adalimumab, has been associated with rare cases of new onset or exacerbation of clinical symptoms and/or radiographic evidence of demyelinating disease. Exercise caution in considering the use of adalimumab in patients with preexisting or recent-onset CNS demyelinating disorders.
Hematologic effects: Rare reports of pancytopenia, including aplastic anemia, have been reported with TNF-blocking agents. Adverse reactions of the hematologic system, including medically significant cytopenia (e.g., leukopenia, thrombocytopenia), have been reported infrequently with adalimumab. The causal relationship of these reports to adalimumab remains unclear. Advise patients to seek immediate medical attention if they develop signs and symptoms suggestive of blood dyscrasias or infection (e.g., bleeding, bruising, pallor, persistent fever) while on adalimumab. Consider discontinuation of adalimumab therapy in patients with confirmed significant hematologic abnormalities.
Congestive heart failure: Cases of worsening congestive heart failure (CHF) and new-onset CHF have been reported with TNF blockers. Cases of worsening CHF have also been observed with adalimumab. Adalimumab has not been formally studied in patients with CHF; however, in clinical trials of another TNF blocker, a higher rate of serious CHF-related adverse reactions was observed. Exercise caution when using adalimumab in patients who have heart failure and monitor them carefully.
Autoimmunity: Treatment with adalimumab may result in the formation of autoantibodies and, rarely, in the development of a lupus-like syndrome. If a patient develops symptoms suggestive of a lupus-like syndrome following treatment with adalimumab, discontinue treatment.
Immunizations: In a placebo-controlled clinical trial of patients with RA, no difference was detected in antipneumococcal antibody response between adalimumab and placebo treatment groups when the pneumococcal polysaccharide vaccine and influenza vaccine were coadministered with adalimumab. Similar proportions of patients developed protective levels of anti-influenza antibodies between adalimumab and placebo treatment groups; however, titers in aggregate to influenza antigens were moderately lower in patients receiving adalimumab. The clinical significance of this is unknown.
Patients on adalimumab may receive concurrent vaccinations, except for live vaccines. No data are available on the secondary transmission of infection by live vaccines in patients receiving adalimumab. It is recommended that juvenile idiopathic arthritis patients, if possible, be brought up to date with all immunizations in agreement with current immunization guidelines prior to initiating adalimumab therapy.
Immunosuppression: The possibility exists for TNF-blocking agents, including adalimumab, to affect host defenses against infections and malignancies because TNF mediates inflammation and modulates cellular immune responses.
In a study of 64 patients with RA treated with adalimumab, there was no evidence of depression of delayed-type hypersensitivity, depression of immunoglobulin levels, or change in enumeration of effector T and B cells and NK cells, monocyte/macrophages, and neutrophils. The impact of treatment with adalimumab on the development and course of malignancies as well as active and/or chronic infections is not fully understood. The safety and efficacy of adalimumab in patients with immunosuppression have not been evaluated.
Immunogenicity: Patients in studies RA-I, RA-II, and RA-III were tested at multiple time points for antibodies to adalimumab during the 6- to 12-month period. Approximately 5% (58/1,062) of adult RA patients receiving adalimumab developed low-titer antibodies to adalimumab at least once during treatment, which were neutralizing in vitro. Patients treated with concomitant methotrexate had a lower rate of antibody development than patients on adalimumab monotherapy (1% vs. 12%). No apparent correlation of antibody development to adverse reactions was observed. With monotherapy, patients receiving every-other-week dosing may develop antibodies more frequently than those receiving weekly dosing. In patients receiving the recommended dosage of 40 mg every other week as monotherapy, the American College of Rheumatology (ACR) 20 response was lower among antibody-positive patients than among antibody-negative patients. The long-term immunogenicity of adalimumab is unknown.
In patients with juvenile idiopathic arthritis, adalimumab antibodies were identified in 16% of adalimumab-treated patients. In patients receiving concomitant methotrexate, the incidence was 6% compared with 26% receiving adalimumab monotherapy.
In patients with ankylosing spondylitis, the rate of development of antibodies to adalimumab in adalimumab-treated patients was comparable with patients with RA. In patients with psoriatic arthritis, the rate of antibody development in patients receiving adalimumab monotherapy was comparable with patients with RA; however, in patients receiving concomitant methotrexate, the rate was 7% compared with 1% in RA. In patients with Crohn disease, the rate of antibody development was 2.6%. The immunogenicity rate was 8% for plaque psoriasis patients who were treated with adalimumab monotherapy.
The data reflect the percentage of patients whose test results were considered positive for antibodies to adalimumab in an enzyme-linked immunosorbent assay and are highly dependent on the sensitivity and specificity of the assay. The observed incidence of antibody (including neutralizing antibody) positivity in an assay is highly dependent on several factors, including assay sensitivity and specificity, assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to adalimumab with the incidence of antibodies to other products may be misleading.
Hypersensitivity reactions: In postmarketing experience, anaphylaxis and angioneurotic edema have been reported rarely following adalimumab administration. If an anaphylactic or other serious allergic reaction occurs, discontinue administration of adalimumab immediately and institute appropriate therapy. In adults in clinical trials of adalimumab, allergic reactions (e.g., allergic rash, anaphylactoid reaction, fixed drug reaction, nonspecified drug reaction, urticaria) have been observed in approximately 1% of patients.
Children: Safety and effectiveness of adalimumab in children for uses other than juvenile idiopathic arthritis have not been established.
In the juvenile idiopathic arthritis study, adalimumab was shown to reduce signs and symptoms of active polyarticular juvenile idiopathic arthritis in patients 4 to 17 years of age.
Adalimumab has not been studied in children younger than 4 years of age, and there are limited data on adalimumab treatment in children weighing less than 15 kg.
Safety of adalimumab in children was generally similar to that observed in adults, with certain exceptions.
Elderly: A total of 519 RA patients 65 years of age and older, including 107 patients 75 years of age and older, received adalimumab in clinical studies RA-I through RA-IV. No overall difference in effectiveness was observed between these subjects and younger subjects.
The frequency of serious infection and malignancy among adalimumab-treated subjects older than 65 years of age was higher than for those younger than 65 years of age. Because there is a higher incidence of infections and malignancies in the elderly population in general, use caution when treating elderly patients.
Monitoring: Closely monitor patients who develop a new infection while undergoing treatment with adalimumab. Monitor patients for signs and symptoms of active TB, including patients who had a negative tuberculin skin test. Monitor heart failure patients carefully. Closely monitor patients who are carriers of HBV and require treatment with TNF blockers for clinical and laboratory signs of active HBV infections throughout therapy and for several months following termination of therapy.
|96372||Therapeutic, prophylactic, or diagnostic injection (specify substance or drug); subcutaneous or intramuscular|
|J0135||Adalimumab (Humira®) Injection 20 mg|
ICD-9 Diagnoses Codes That Support Medical Necessity:
|555.0 – 555.9||Crohn’s disease|
|714.0 – 714.2||Rheumatoid arthritis|
|714.30 – 714.33||Juvenile chronic polyarthritis|
|714.4||Chronic postrheumatic arthropathy|
|714.81||Other specified inflammatory polyarhtropathies|
|714.9||Unspecified inflammatory polyarthropathy|
|K50.00||Crohn’s disease of small intestine without complications|
|K50.10||Crohn’s disease of large intestine without complications|
|K50.80||Crohn’s disease of both small and large intestine without complications|
|K50.90||Crohn’s disease, unspecified, without complications|
|L40.54||Psoriatic juvenile arthropathy|
|L40.59||Other psoriatic arthropathy|
|M05.00||Felty’s syndrome, unspecified site|
|M05.10||Rheumatoid lung disease with rheumatoid arthritis of unspecified site|
|M05.30||Rheumatoid heart disease with rheumatoid arthritis of unspecified site|
|M05.60||Rheumatoid arthritis of unspecified site with involvement of other organs and systems|
|M06.1||Adult-onset Still’s disease|
|M06.9||Rheumatoid arthritis, unspecified|
|M08.00||Unspecified juvenile rheumatoid arthritis of unspecified site|
|M08.3||Juvenile rheumatoid polyarthritis (seronegative|
|M08.40||Pauciarticular juvenile rheumatoid arthritis, unspecified site|
|M12.00||Chronic postrheumatic arthropathy [Jaccoud], unspecified site|
|M45.9||Ankylosing spondylitis of unspecified sites in spine|
Refer to section entitled POSITION STATEMENT.
Federal Employee Program (FEP): Follow FEP guidelines.
State Account Organization (SAO): Follow SAO guidelines.
Medicare Part D: BCBSF has delegated to Prime Therapeutics authority to make coverage determinations for the Medicare Part D services referenced in this guideline.
Antirheumatic: An agent that relieves or prevents musculoskeletal pain.
Crohn’s diseasse: A chronic granulomatous inflammatory disease of unknown etiology, involving any part of the gastrointestinal tract from mouth to anus, but commonly involving the terminal ileum with scarring and thickening of the bowel wall.
DMARDs: An acronym for disease-modifying antirheumatic drugs.
Psoriatic arthritis: a severe form of arthritis accompanied by inflammation, psoriasis of the skin or nails, and a negative test for rheumatoid factor.
Rheumatic: A term referring to a disorder or condition that causes pain or stiffness in the joints, muscles, or bone of the musculoskeletal system.
Rheumatoid arthritis: An inflammatory disease of the synovium, or lining of the joint, that results in pain, stiffness, and swelling of multiple joints. The inflammation may extend to other joints and cause bone and cartilage erosion, joint deformities, movement problems, and activity limitations.
Etanercept (Enbrel®), 09-J0000-38
Infliximab (Remicade®), 09-J0000-39
Anakinra (Kineret®), 09-J0000-45
Rituximab (Rituxan®), 09-J0000-59
Abatacept (Orencia®), 09-J0000-67
Certolizumab Pegol (Cimzia®), 09-J0000-77
Alefacept (Amevive®), 09-J0000-78
Rilonacept (Arcalyst™), 09-J0000-89
Golimumab (Simponi™), 09-J1000-11
Canakinumab (Ilaris®) Injection, 09-J1000-14
Ustekinumab (Stelara™), 09-J1000-16
Tocilizumab (Actemra®) IV, 09-J1000-21
|DMARD Generic Name||DMARD Brand Name|
|Auranofin (oral gold)||Ridaura®|
|Gold sodium thiomalate (injectable gold)||Myochrysine®|
|Sulfasalazine||Azulfidine®, Azulfidine EN-Tabs®|
- Abbott Laboratories. Letter, “IMPORTANT DRUG WARNING” dated 11/05/04.
- Abbott Laboratories. Press Release. Abbott Seeks U.S. and E.U. Regulatory Approval for Humira® (adalimumab) in Psoriasis. 04/02/07.
- American Journal of Respiratory and Critical Care Medicine (2003; 167:603-62).
- American Medical Association CPT Coding, 2009 professional edition.
- Behm BW, Bickston SJ. Tumor necrosis factor-alpha antibody for maintenance of remission in Crohn’s disease. Cochrane Database of Systematic Reviews 2008, Issue 1. Art. No.: CD006893. DOI: 10.1002/14651858.CD006893.
- Clinical Pharmacology, copyright® 2009.
- Cush JJ, Biologic Treatments for Rheumatoid Arthritis. American College of Rheumatology 2006.
- DRUGDEX®, accessed 06/24/10.
- eHealth MD: Autoimmune Disorders, 2005.
- Facts & Comparisons, 4.0, accessed 06/24/10.
- Food and Drug Administration (FDA). Orphan designations and approvals list. 2005.
- Gordon KB et. al. Clinical response to adalimumab treatment in patients with moderate to severe psoriasis. J Am Acad Dermatol 10.1016/j, haad. 05/27/06.
- Guidelines for the Management of Rheumatoid Arthritis 2002 Update. American College of Rheumatology Subcommittee on Rheumatoid Arthritis Guidelines. ARTHRITIS & RHEUMATISM Vol. 46, No. 2, February 2002, pp 328 – 346.
- HAYES, Inc. New Drug for Crohn’s Disease Approved. Lansdale, PA: HAYES, Inc. 03/06/07.
- HIPAA Space, HCPCS Codes Lookup, Copyright® 2004 – 2010. Accessed 06/29/10.
- Humira® Prescribing Information, November 2009.
- ICD-9 Data.com. Accessed 06/29/10.
- Mease PJ, Gladman DD, Ritchlin CT et al. Adalimumab for the treatment of patients with moderately to severely active psoriatic arthritis: Results of a double-blind, randomized, placebo-controlled trial. Arthritis Rheum. 2005 Oct; 52(10): 3279-89.
This Medical Coverage Guideline (MCG) was approved by the BCBSF Pharmacy Policy Committee on 07/14/10.
|01/01/05||New Medical Coverage Guideline.|
|08/15/05||Revised and Updated: Updated description, dosage/administration. Deleted precautions, updated when services are not covered, billing/coding information, and definitions, table 1, references.|
|11/15/05||Updated when services are covered for psoriatic arthritis, updated ICD-9 codes, definitions, and references.|
|11/15/06||Scheduled review: added indication of ankylosing spondylitis, added ICD-9 code, corrected CPT-4 coding and updated references.|
|01/01/07||MCG revised to include Medicare Part D as program exception.|
|04/15/07||Revision; consisting of adding Crohn’s disease indication and ICD-9 code, related guidelines and definitions.|
|06/15/07||Review and revision; consisting of reformatting, updating related guidelines and references.|
|03/15/08||Revision; consisting of adding plaque psoriasis and juvenile idiopathic arthritis (JIA) as covered indications, rewording coverage criteria for Crohn’s disease, updated dosage and administration section, added ICD-9 codes and updated references.|
|05/15/08||Review and revision; consisting of reformatting, adding a black box warning under “PRECAUTIONS”, adding related guideline and updating references.|
|09/15/08||Revision of guideline; consisting of adding 3 ICD-9 codes.|
|01/01/09||Annual HCPCS coding update: deleted code 90772; added code 96372.|
|09/15/09||Review and revision; consisting of updating references, boxed warning and ICD-9 coding.|
|04/15/10||Revision; consisting of adding specific continuation criteria.|
|08/15/10||Review and revision; consisting of adding age criteria to all indications, updated precautions and references.|
|01/15/11||Revision; consisting of adding ICD-10 codes.|
|04/01/11||Revision; consisting of adding dosage limitations.|
Data from: http://mcgs.bcbsfl.com/index.cfm