Print

Date Printed: June 23, 2017: 11:45 AM

Private Property of Blue Cross and Blue Shield of Florida.
This medical policy (medical coverage guideline) is Copyright 2017, Blue Cross and Blue Shield of Florida (BCBSF). All Rights Reserved. You may not copy or use this document or disclose its contents without the express written permission of BCBSF. The medical codes referenced in this document may be proprietary and owned by others. BCBSF makes no claim of ownership of such codes. Our use of such codes in this document is for explanation and guidance and should not be construed as a license for their use by you. Before utilizing the codes, please be sure that to the extent required, you have secured any appropriate licenses for such use. Current Procedural Terminology (CPT) is copyright 2017 American Medical Association. All Rights Reserved. No fee schedules, basic units, relative values, or related listings are included in CPT. The AMA assumes no liability for the data contained herein. Applicable FARS/DFARS restrictions apply to government use. CPT® is a trademark of the American Medical Association. The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

09-J0000-45

Original Effective Date: 01/01/05

Reviewed: 08/10/16

Revised: 10/01/16

Subject: Anakinra (Kineret®)

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 
           
Related Guidelines Other References Updates  
           

DESCRIPTION:

Anakinra (Kineret) is a recombinant, non-glycosylated form of the human Interleukin-1 receptor antagonist (IL-1Ra) that differs from the naturally occurring human interleukin-1 (IL-1) receptor antagonist by the addition of one N-terminal methionine. IL-1, a dominant cytokine associated with rheumatoid arthritis, is produced in response to inflammatory stimuli and mediates inflammatory and immunological responses. IL-1 causes cartilage degradation by its induction of the rapid loss of proteoglycans, stimulation of bone resorption, and inflammation due to prostaglandin and cyclooxygenase-2 production. In normal joints, endogenous IL-1Ra adheres to the IL-1 receptor on target cells and blocks the binding of IL-1 thus inhibiting the effects of IL-1. In joints effected by rheumatoid arthritis (RA), there is an over-expression of IL-1 that cannot be sufficiently countered by endogenous IL-1Ra. Anakinra exerts its action in the same manner as endogenous IL-1Ra by blocking the biologic activity of interleukin-1 (IL-1) due to competitive inhibition of IL-1 binding to the IL-1 type I receptor (IL-1RI).

Anakinra was approved by the US Food and Drug Administration (FDA) in 2001 for treatment of RA in persons 18 years of age or older who have failed one or more disease-modifying anti-rheumatic drugs (DMARDs). While anakinra can be used in combination with DMARDs, it should not be used concomitantly with tumor necrosis factor (TNF) antagonists. The 2015 American College of Rheumatology (ACR) RA guidelines do not discuss the role of anakinra due to infrequent use and/or lack of new data for this agent. In 2012, the FDA expanded the approval of anakinra to include treatment of cryopyrin-associated periodic syndromes (CAPS), specifically neonatal-onset multisystem inflammatory disease (NOMID). NOMID was previously designated by the FDA as an orphan indication in 2010. Anakinra also has an orphan drug designation for “treatment of Still's disease including systemic juvenile idiopathic arthritis and adult-onset Still's disease” (2015).

In the 2015 TACIT pragmatic, non-inferiority, randomized controlled trial, 205 persons with established moderate to severe RA received either an anti-TNF biologic with one DMARD (e.g., methotrexate), or conventional DMARD therapy titrated upward to include combination therapy. Most persons in the DMARD group eventually received 2 or 3 DMARDs in combination (e.g., methotrexate + leflunomide). The DMARD group was shown to be non-inferior to the anti-TNF group for the primary outcome of disability measured by a patient-recorded health assessment questionnaire at 12 months with a numerical advantage towards the DMARD group. Further supporting use of combination DMARD therapy, the 2-year follow-up of the SWEFOT trial (438 persons with methotrexate-refractory RA) showed no difference in utility or QALY gain over 21 months when comparing methotrexate + infliximab vs. methotrexate + sulfasalazine + hydroxychloroquine.

While methotrexate must be avoided in women who are pregnant or trying to become pregnant, sulfasalazine has adequate data supporting safe use (pregnancy Category B), and is consider a preferred DMARD when given with folic acid if treatment is clinically necessary. Hydroxychloroquine, cyclosporine, and anti-TNF biologics are also considered to be low-risk options during pregnancy.

POSITION STATEMENT:

Comparative Effectiveness

The Food and Drug Administration has deemed the drug(s) or biological product(s) in this coverage policy to be appropriate for self-administration or administration by a caregiver (i.e., not a healthcare professional). Therefore, coverage (i.e., administration) in a provider-administered setting such as an outpatient hospital, ambulatory surgical suite, physician office, or emergency facility is not considered medically necessary.

NOTE: etanercept (Enbrel), adalimumab (Humira), golimumab (Simponi), and ustekinumab (Stelara) are preferred self-administered products.

NOTE: if the member has failed previous biologic therapy, other than anakinra, that is FDA-approved for the requested indication listed below, the member is not required to try and fail additional non-biologic prerequisite therapy (e.g., for RA, if member has previously tried and failed etanercept, but does not have a history of combination DMARD failure, they do not have to try and fail two DMARDs in combination to meet medical necessity criteria).

Initiation of anakinra (Kineret) meets the definition of medical necessity when ALL of the following criteria are met:

1. Anakinra is NOT used in combination with ANY of the following:

a. abatacept (Orencia)

b. adalimumab (Humira)

c. apremilast (Otezla)

d. certolizumab (Cimzia)

e. etanercept (Enbrel)

f. golimumab (Simponi)

g. infliximab (Remicade)

h. Ixekizumab (Taltz)

i. secukinumab (Cosentyx)

j. tocilizumab (Actemra)

k. tofacitinib (Xeljanz)

l. ustekinumab (Stelara)

m. vedolizumab (Entyvio)

2. The indication is ANY of the following:

a. Rheumatoid arthritis (RA) when ALL of the following criteria are met:

1. Member’s disease is moderately to severely active

2. Member has tried and failed therapy with at least TWO DMARDs (e.g., hydroxychloroquine, methotrexate, sulfasalazine, leflunomide) used in combination. Failure of only one DMARD is sufficient if member has a contraindication to BOTH methotrexate AND either sulfasalazine or hydroxychloroquine (the specific contraindications must be provided; pregnancy is not considered a contraindication to the use of sulfasalazine or hydroxychloroquine)

3. Member has tried and failed or has a contraindication to TWO or more of the following self-administered biologics (the specific contraindication must be provided):

a. etanercept (Enbrel)

b. adalimumab (Humira)

c. golimumab (Simponi)

4. Member is 18 years of age or older

5. The member’s dosage does not exceed 100 mg daily

b. Neonatal-onset multisystem inflammatory disease (NOMID) [a.k.a., chronic infantile neurologic cutaneous articular (CINCA) syndrome] when BOTH of the following criteria are met:

1. Member has tried and failed ONE or more or has a contraindication to ALL of the following:

a. Non-steroidal anti-inflammatory drugs (NSAIDs) (e.g., ibuprofen, meloxicam)

b. Disease-modifying anti-rheumatic drugs (DMARDs) (e.g., methotrexate, sulfasalazine, cyclosporine, leflunomide)

c. Corticosteroids (e.g., methylprednisolone, dexamethasone, prednisolone)

2. The member’s dosage does not exceed 8 mg/kg/day

c. Multicentric Castleman's disease (CD)

1. Anakinra is used as monotherapy for treatment of the member’s CD

2. Member has tried and failed at least TWO prior treatments for CD

3. The member’s dosage does not exceed 100 mg daily

Approval duration: 6 months

Continuation of anakinra meets the definition of medical necessity when ALL of the following criteria are met:

1. Member has a history of beneficial response to anakinra therapy

2. An authorization/reauthorization for anakinra has been previously approved by Florida Blue or another health plan in the past 2 years for the treatment of RA, NOMID, or CD, OR the member previously met ALL indication-specific initiation criteria.

3. Anakinra is NOT used in combination with ANY of the following:

a. Abatacept (Orencia)

b. Adalimumab (Humira)

c. Apremilast (Otezla)

d. Certolizumab (Cimzia)

e. Etanercept (Enbrel)

f. Golimumab (Simponi)

g. Infliximab (Remicade)

h. Ixekizumab (Taltz)

i. Secukinumab (Cosentyx)

j. Tocilizumab (Actemra)

k. Tofacitinib (Xeljanz)

l. Ustekinumab (Stelara)

m. Vedolizumab (Entyvio)

4. The member’s dosage does not exceed the following based on their indication for use:

a. Rheumatoid arthritis: 100 mg/day

b. CINCA/NOMID: 8 mg/kg/day

c. Multicentric Castleman's disease (CD): 100 mg/day

Approval duration: 1 year

Anakinra (Kineret) meets the definition of medical necessity when used to treat the following orphan indication AND associated criteria are met:

1. Still's disease (including systemic juvenile idiopathic arthritis and adult-onset Still's disease)

a. The member has previously failed first-line treatment

b. The member’s dosage does not exceed 100 mg/day

Approval duration: 1 year

Anakinra is considered experimental or investigational when administered for all other indications as there is insufficient clinical evidence to support its use.

DOSAGE/ADMINISTRATION:

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 ITS USAGE.

FDA-approved: anakinra is indicated for reduction in signs and symptoms and slowing the progression of structural damage in moderately to severely active rheumatoid arthritis in persons 18 years of age and older who have failed 1 or more disease-modifying anti-rheumatic drugs (DMARDs). The recommended dose of anakinra is 100 mg/day administered as subcutaneous (SQ) injection. The dose should be administered at approximately the same time every day.

Dose Adjustments

Renal Impairment: a dose of 100 mg every other day should be used in persons with severe renal insufficiency or end stage renal disease (defined as creatinine clearance [CrCl] less than 30 ml/min)

Drug Availability: anakinra is available as a 100 mg/0.67 mL solution for injection.

PRECAUTIONS:

CONTRAINDICATIONS

Anakinra is contraindicated in persons with a known hypersensitivity to E. coli-derived proteins or in those known to have a hypersensitivity to the active or inactive ingredients.

WARNINGS AND PRECAUTIONS

Serious infections: discontinue if serious infection develops and do no initiate therapy in persons with active infections.

Concomitant TNF-antagonist therapy: do not use in combination with TNF-antagonist therapy (e.g., adalimumab, etanercept, infliximab, certolizumab, golimumab)

Hypersensitivity: hypersensitivity reactions, including anaphylactic reactions and angioedema, have been reported.

Immunosuppression: the impact of treatment with anakinra on active and/or chronic infections and the development of malignancies is unknown.

Neutrophil count: assess neutrophil counts prior to therapy initiation, monthly for 3 months following initiation, and quarterly thereafter for a period up to 1 year.

Vaccinations: do not administer live vaccines in members receiving anakinra.

BILLING/CODING INFORMATION:

HCPCS Coding:

J3590

Unclassified biologics

ICD-10 Diagnoses Codes That Support Medical Necessity: (Effective 10/01/15)

D47.Z2

Castleman disease

G03.1

Chronic meningitis [for neonatal-onset multisystem inflammatory disease (NOMID) only]

L50.8

Urticaria [for NOMID only]

M05.00 – M05.09

Felty's syndrome

M05.10 – M05.19

Rheumatoid lung disease with rheumatoid arthritis

M05.20 – M05.29

Rheumatoid vasculitis with rheumatoid arthritis

M05.30 – M05.39

Rheumatoid heart disease with rheumatoid arthritis

M05.40 – M05.49

Rheumatoid myopathy with rheumatoid arthritis

M05.50 – M05.59

Rheumatoid polyneuropathy with rheumatoid arthritis

M05.60 – M05.69

Rheumatoid arthritis with involvement of other organs and systems

M05.70 – M05.79

Rheumatoid arthritis with rheumatoid factor without organ or systems involvement

M05.80 – M05.89

Other rheumatoid arthritis with rheumatoid factor

M05.9

Rheumatoid arthritis with rheumatoid factor, unspecified

M06.00 – M06.09

Rheumatoid arthritis without rheumatoid factor

M06.1

Adult-onset Still's disease

M06.20 – M06.29

Rheumatoid bursitis

M06.30 – M06.39

Rheumatoid nodule

M06.80 – M06.89

Other specified rheumatoid arthritis

M06.9

Rheumatoid arthritis, unspecified

M08.20 – M08.29

Juvenile rheumatoid arthritis with systemic onset

Q87.89

Other specified congenital malformation syndromes, not elsewhere classified

[for NOMID only]

REIMBURSEMENT INFORMATION:

Refer to section entitled POSITION STATEMENT.

PROGRAM EXCEPTIONS:

Federal Employee Program (FEP): Follow FEP guidelines.

State Account Organization (SAO): Follow SAO guidelines.

Medicare Advantage Products: No National Coverage Determination (NCD) and/or Local Coverage Determination (LCD) were found at the time of the last guideline review date.

Medicare Part D: Florida Blue has delegated to Prime Therapeutics authority to make coverage determinations for the Medicare Part D services referenced in this guideline.

DEFINITIONS:

.

DMARDs: An acronym for disease-modifying antirheumatic drugs.

Neonatal-onset multisystem inflammatory disease (NOMID): also known as chronic infantile neurologic cutaneous articular (CINCA) syndrome, is a rare, congenital, systemic, inflammatory condition distinguished by fever, rash, joint disease, and central nervous system (CNS) disease. The hallmark of NOMID is onset during infancy or early childhood. NOMID is the most severe form of the cryopyrin associated periodic syndromes (CAPS) caused by mutations in the CIAS1/NLRP3 gene.

Rheumatoid arthritis: An inflammatory disease of the synovium, or lining of the joint which 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.

RELATED GUIDELINES:

Abatacept (Orencia®), 09-J0000-67

Adalimumab (Humira®), 09-J0000-46

Apremilast (Otezla), 09-J2000-19

Canakinumab (Ilaris®) Injection, 09-J1000-14

Certolizumab Pegol (Cimzia®), 09-J0000-77

Etanercept (Enbrel®), 09-J0000-38

Golimumab (Simponi™), 09-J1000-11

Infliximab (Remicade®) and Infliximab-dyyb (Inflectra®), 09-J0000-39

Rilonacept (Arcalyst™), 09-J0000-89

Rituximab (Rituxan®), 09-J0000-59

Tocilizumab (Actemra®) Injection, 09-J1000-21

Tofacitinib (Xeljanz®), 09-J1000-86

Vedolizumab (Entyvio), 09-J2000-18

OTHER:

Table 1: DMARDs

DMARD Generic Name

DMARD Brand Name

Auranofin (oral gold)

Ridaura

Azathioprine

Imuran

Chlorambucil

Leukeran

Cyclophosphamide

Cytoxan

Cyclosporine

Neoral, Sandimmune

Gold sodium thiomalate (injectable gold)

Myochrysine

Hydroxychloroquine sulfate

Plaquenil

Leflunomide

Arava

Methotrexate

Rheumatrex, Trexall

Minocycline

Minocin

Penicillamine

Cuprimine, Depen

Sulfasalazine

Azulfidine, Azulfidine EN-Tabs

Grading of Severity of Rheumatoid Arthritis

Severity

Criteria

Mild

Joint pain
Inflammation of at least 3 joints
No inflammation in tissues other than the joints
Usually, a negative result on a rheumatoid factor test
An elevated erythrocyte sedimentation rate (ESR) or C reactive protein (CRP) level
No evidence of bone or cartilage damage on x-rays

Moderate

Between 6 and 20 inflamed joints
Usually no inflammation in tissues other than the joints
An elevated ESR or CRP levels
A positive rheumatoid factor test or anti-cyclic citrullinated peptide (anti-CCP) antibodies
Evidence of inflammation but no evidence of bone damage on x-rays

Severe

More than 20 persistently inflamed joints or a rapid loss of functional abilities
Elevated ESR or CRP levels
Anemia related to chronic illness
Low blood albumin level
A positive rheumatoid factor test, often with a high level
Evidence of bone and cartilage damage on x-ray
Inflammation in tissues other than joints

REFERENCES:

  1. Clinical Pharmacology [database online]. Tampa, FL: Gold Standard, Inc.;2015. URL www.clinicalpharmacilogy-ip.com, Accessed 7/7/16.
  2. FDA Orphan Drug Designations and Approvals [Internet]. Washington, D.C. [cited 2016 July 7]. Available from: http://www.accessdata.fda.gov/scripts/opdlisting/oopd/.
  3. Graudal N, Hubeck-Graudal T, Tarp S, et al. Effect of combination therapy on joint destruction in rheumatoid arthritis: a network meta-analysis of randomized controlled trials. PLoS One. 2014 Sep 22;9(9):e106408.
  4. Karlsson JA, Neovius M, Nilsson JA, et al. Addition of infliximab compared with addition of sulfasalazine and hydroxychloroquine to methotrexate in early rheumatoid arthritis: 2-year quality-of-life results of the randomised, controlled, SWEFOT trial. Ann Rheum Dis. 2013 Dec;72(12):1927-33.
  5. Kineret (anakinra) [package insert]. Swedish Orphan Biovitrum AB. Stockholm, Sweden. July 2015.
  6. Krause ML, Amin A, and Makol A. Use of DMARDs and biologics during pregnancy and lactation in rheumatoid arthritis: what the rheumatologist needs to know. Ther Adv Musculoskelet Dis. 2014 Oct; 6(5): 169–184.
  7. Mertens M, Singh JA. Anakinra for rheumatoid arthritis. Cochrane Database of Systematic Reviews 2009, Issue 1. Art. No.: CD005121. DOI: 10.1002/14651858. CD005121.pub3.
  8. Micromedex® Healthcare Series [Internet Database]. Greenwood Village, Colo: Thomson Healthcare. Updated periodically. Accessed 7/7/16.
  9. National Collaborating Centre for Chronic Conditions (UK). Rheumatoid Arthritis: National Clinical Guideline for Management and Treatment in Adults. London: Royal College of Physicians (UK); 2009 Feb (updated 2015 Dec).
  10. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology. Version3.2016. Non-Hodgkin’s Lymphomas. Available at http://www.nccn.org/professionals/physician_gls/PDF/nhl.pdf. Accessed 7/7/16.
  11. Rahimi R, Nikfar S, Rezaie A, et al. Pregnancy outcome in women with inflammatory bowel disease following exposure to 5-aminosalicylic acid drugs: a meta-analysis. Reprod. Toxicol;2008:25,271–275.
  12. Scott DL, Ibrahim F, Farewell V, et al. Tumour necrosis factor inhibitors versus combination intensive therapy with conventional disease modifying anti-rheumatic drugs in established rheumatoid arthritis: TACIT non-inferiority randomised controlled trial. BMJ. 2015 Mar 13;350:h1046.
  13. Singh JA, Saag KG, Bridges SL Jr, et al. 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Care Res (Hoboken). 2016 Jan;68(1):1-25.
  14. van Vollenhoven RF, Geborek P, Forslind K, et al. Conventional combination treatment versus biological treatment in methotrexate-refractory early rheumatoid arthritis: 2 year follow-up of the randomised, non-blinded, parallel-group Swefot trial. Lancet. 2012 May 5;379(9827):1712-20.

COMMITTEE APPROVAL:

This Medical Coverage Guideline (MCG) was approved by the BCBSF Pharmacy Policy Committee on 08/10/16.

GUIDELINE UPDATE INFORMATION:

01/01/05

New Medical Coverage Guideline.

08/15/05

Revised and Updated: added description, when services are covered, dose/administration, deleted precautions, updated when services are not covered, other, references, and related internet links.

01/01/06

CPT code update: deleted expired code 90782, and added new code 90772.

09/15/06

Biennial review; updated references and added related guidelines.

01/01/07

MCG revised to include Medicare Part D as a program exception.

07/15/07

Reviewed: maintain current coverage and limitations. Reformatted guideline, updated internet links and references.

07/15/08

Reviewed with no changes in coverage. Added related MCG and updated references and links.

01/01/09

Annual HCPCS coding update: deleted code 90772; added code 96372.

07/15/09

Review and revision; consisting of review of product information, added PRECAUTIONS section and updated the references.

08/15/10

Review and revision; consisting of rewording description, updating precautions and references.

01/15/11

Revision; consisting of adding ICD-10 codes.

04/01/11

Revision; consisting of adding dosage limitations.

08/15/11

Review and revision to guideline; consisting of updating references.

08/15/12

Review and revision to guideline; consisting of reformatting the position statement, updating coding and references.

09/15/12

Revision to guideline; consisting of modifying continuation criteria.

04/15/13

Revision to guideline; consisting of revising and reformatting position statement to include treatment of chronic infantile neurological cutaneous articular syndrome and orphan drug indications; reformatted and revised description, dosage/administration, and precautions sections; updated references and coding; added pertinent definitions.

09/15/13

Review and revision to guideline; consisting of updating position statement, description, program exceptions, and references.

01/01/14

Revision to guideline; consisting of updating position statement.

04/15/14

Revision to guideline; consisting of updating and reformatting position statement.

09/15/14

Review and revision to guideline; consisting of updating position statement, references, and related guidelines.

09/15/15

Review and revision to guideline; consisting of updating description section, position statement, billing/coding, and references.

12/15/15

Revision to guideline consisting of updating description and position statement based on a new orphan indication.

09/15/16

Review and revision to guideline consisting of updating description, position statement, coding/billing, definitions, and references.

10/01/16

Revision: ICD-10 code updates

Date Printed: June 23, 2017: 11:45 AM