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09-J1000-21

Original Effective Date: 05/15/10

Reviewed: 08/10/16

Revised: 07/15/17

Subject: Tocilizumab (Actemra®) Injection

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.

           
Position Statement Dosage/ Administration Billing/Coding Reimbursement Program Exceptions Definitions
           
Related Guidelines Other References Updates
           

DESCRIPTION:

Tocilizumab (Actemra®) is a monoclonal antibody that binds to and ultimately blocks soluble and membrane-bound interleukin-6 (IL-6). Interleukin-6 is a proinflammatory cytokine that affects the function of neutrophils, T-cells, B-cells, monocytes, and osteoclasts and is over-expressed in the synovial tissue in patients with rheumatoid arthritis (RA). Additionally, IL-6 has been linked to other inflammatory conditions including systemic juvenile idiopathic arthritis (SJIA) and polyarticular juvenile idiopathic arthritis (PJIA).

Tocilizumab was initially approved by the US Food and Drug Administration (FDA) in January 2010 to reduce the signs and symptoms of moderate to severe RA in adults who have had an inadequate response to one or more tumor necrosis factor (TNF) antagonists. The indication was revised in October 2012 to persons with an inadequate response to one or more disease-modifying antirheumatic drugs (DMARDs). In 2011, tocilizumab was approved alone or in combination with methotrexate for the treatment of active SJIA in children 2 years of age or older and in April 2013 tocilizumab was granted approval for the treatment of active PJIA in children 2 years of age or older. In May 2017, tocilizumab was FDA-approved for the treatment of giant cell arteritis (CGA) in adult patients in combination with a tapering course of glucocorticoids. It is the first FDA-approved treatment for this disease. The subcutaneous formulation of tocilizumab was first approved in October 2013 for RA; this formulation is indicated for treatment of RA and GCA only. Actemra also received orphan designation (but not an FDA-approved indication) for the treatment of systemic sclerosis in 2013.

American College of Rheumatology (ACR) guidelines for treatment of RA was updated in 2015. The RA guidelines support the use of a non-TNF biologic (e.g., abatacept) in the following scenarios: (1) patients with early RA if disease activity remains moderate or high despite DMARD monotherapy (with or without glucocorticoids), use combination DMARDS or a TNFi or a non-TNF biologic (all choices with or without methotrexate (MTX), in no particular order of preference); (2) patients with established RA if disease activity remains moderate or high despite DMARD monotherapy, use combination traditional DMARDS or add a TNFi or a non-TNF biologic or tofacitinib (all choices with or without MTX, in no particular order of preference); (3) patients with established RA if disease activity remains moderate or high despite use of a single TNFi, use a non-TNF biologic, with or without MTX; (4) patients with established RA if disease activity remains moderate or high despite use of a single non-TNF biologic, use another non-TNF biologic, with or without MTX; (5) patients with established RA if disease activity remains moderate or high despite use of multiple (2+) sequential TNFi therapies, first use a non-TNF biologic, with or without MTX; (6) patients with established RA if disease activity remains moderate or high despite use of at least one TNFi and at least one non-TNF biologic, first use another non-TNF biologic, with or without MTX. Non-TNF biologics are also recommended when patients must avoid a TNFi due to certain high-risk conditions [i.e., congestive heart failure, lymphoproliferative disorders, and previous serious infection (abatacept only)]. 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 if given with folic acid when treatment is clinically necessary. Hydroxychloroquine, cyclosporine, and anti-TNF biologics are also considered to be low-risk options during pregnancy.

While the following studies do not include tocilizumab, they support the use of combination DMARD therapy as a valid option for patients with established moderate to severe RA. 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.

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) of the subcutaneous formulation of tocilizumab in a provider-administered setting such as an outpatient hospital, ambulatory surgical suite, physician office, or emergency facility is not considered medically necessary. This statement does not apply to the intravenous (IV) formulation of tocilizumab.

NOTE: Adalimumab (Humira), etanercept (Enbrel), and golimumab (Simponi) are the preferred self-administered biologic products for rheumatoid arthritis (RA).

*NOTE: Members with RA initiated and maintained on intravenous (IV) tocilizumab therapy are NOT required to have had an inadequate response to two preferred self-administered (i.e., subcutaneous) biologic products. However, members with RA transitioning to the subcutaneous formulation after an initial IV dose must still meet the preferred self-administered biologic product requirement.

NOTE: if the member has had an inadequate therapeutic response to previous biologic therapy, other than tocilizumab, that is FDA-approved for the requested indication listed in Table 1, the member is NOT required to have had an inadequate therapeutic response to additional non-biologic prerequisite therapy (e.g., for RA, if the member has previously had an inadequate therapeutic response to etanercept, but does not have a history of inadequate response to combination DMARDs, they do not have to try to two DMARDs in combination to meet medical necessity criteria). However, members with RA must still meet the two preferred self-administered (i.e., subcutaneous) biologic product requirement.

Initiation of tocilizumab (Actemra) meets the definition of medical necessity when BOTH of the following are met

1. Tocilizumab is administered for an indication listed in Table 1 and ALL of the indication-specific and maximum allowable dosage criteria are met

2. Tocilizumab is NOT administered concomitantly with ANY of the following:

a. Abatacept (Orencia)

b. Adalimumab (Humira)

c. Anakinra (Kineret)

d. Apremilast (Otezla)

e. Certolizumab (Cimzia)

f. Etanercept (Enbrel)

g. Golimumab (Simponi)

h. Infliximab (Remicade)

i. Ixekizumab (Taltz)

j. Secukinumab (Cosentyx)

k. Tofacitinib (Xeljanz)

l. Ustekinumab (Stelara)

m. Vedolizumab (Entyvio)

Table 1

Indications and Specific Criteria

Indication

Specific Criteria

Maximum Allowable Dose

Rheumatoid Arthritis (RA)

(IV or SQ)

When ALL of the following are met:

1. Member’s disease is moderately to severely active

2. Member has had an inadequate therapeutic response to at least TWO DMARDs (e.g., hydroxychloroquine, methotrexate, sulfasalazine, leflunomide) used in combination. Inadequate therapeutic response to 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. EITHER of the following (“a” or “b”)*:

a. Member has had an inadequate therapeutic response, has persistent and intolerable adverse effect(s), or has a contraindication to TWO or more of the following self-administered biologics (the specific adverse effect(s) and/or contraindications must be provided)

• Adalimumab (Humira)

• Etanercept (Enbrel)

• Golimumab (Simponi)

b. Member should consider alternatives to the use of an anti-TNF biologic due to a product warning and precaution for ANY of the following (the specific condition must be provided):

• Current or worsening congestive heart failure

• Previously treated lymphoproliferative disorder
(e.g., leukemias, lymphomas)#

#The 2015 ACR guideline gives the use of rituximab over a TNFi a strong recommendation, while the use of tocilizumab over a TNFI is a conditional recommendation

4. Member is 18 years of age or older

IV: 8 mg/kg (maximum of 800 mg) every 4 weeks

SQ: 162 mg every week

Giant Cell Arteritis (GCA)

When ALL of the following are met:

1. Member has active disease as defined by BOTH of the following (“a” and “b”):

a. Presence of cranial symptoms, OR symptoms of polymyalgia rheumatica

b. ESR ≥30 mm/hr, OR CRP ≥1 mg/dL

2. Member is currently receiving corticosteroid treatment for their GCA

3. One goal of treatment is to reduce the current daily dose of the corticosteroid

4. Member is 18 years of age or older

SQ: 162 mg every week

Systemic Juvenile Idiopathic Arthritis (SJIA) [previously known as Systemic Juvenile Rheumatoid Arthritis (SJRA)]

(IV ONLY)

When ALL of the following are met:

1. Member’s disease is active (e.g., member has fever or other systemic manifestations of SJIA)

2. Member’s disease has persisted for 6 months or more

3. Member has had an inadequate therapeutic response to, or has a contraindication to ONE or more DMARDs (e.g., hydroxychloroquine, leflunomide, methotrexate)

4. Member is 2 years of age or older

IV: 12 mg/kg every 2 weeks

Polyarticular Juvenile Idiopathic Arthritis (PJIA) [previously known as Polyarticular Juvenile Rheumatoid Arthritis (PJRA)]

(IV ONLY)

When BOTH of the following are met:

1. When the member has had an inadequate therapeutic response to, or has a contraindication to ONE or more DMARDs (e.g., methotrexate, sulfasalazine, leflunomide)

2. Member is 2 years of age or older

IV: 10 mg/kg every 4 weeks

Unicentric Castleman's Disease (CD)

(IV ONLY)

When ALL of the following are met:

1. Used as monotherapy for treatment of CD

2. Member’s disease is relapsed or refractory

3. Member is HIV-negative

4. Member is human herpesvirus-8-negative

IV: 12 mg/kg every 2 weeks

Multicentric Castleman's Disease (CD)

(IV ONLY)

When ALL of the following are met:

1. Used as monotherapy for treatment of CD

2. Members disease is relapsed or refractory

3. Member has had an inadequate therapeutic response to at least TWO prior treatments

IV: 12 mg/kg every 2 weeks

DMARD: disease modifying anti-rheumatic drug; ESR: erythrocyte sedimentation rate; CRP: C-reactive protein

*NOTE: Members with RA initiated and maintained on intravenous (IV) tocilizumab therapy are NOT required to have had an inadequate response to two preferred self-administered (i.e., subcutaneous) biologic products. However, members with RA transitioning to the subcutaneous formulation after an initial IV dose must still meet the preferred self-administered biologic product requirement.

NOTE: if the member has had an inadequate therapeutic response to previous biologic therapy, other than tocilizumab, that is FDA-approved for the requested indication listed in Table 1, the member is NOT required to have had an inadequate therapeutic response to additional non-biologic prerequisite therapy (e.g., for RA, if the member has previously had an inadequate therapeutic response to etanercept, but does not have a history of inadequate response to combination DMARDs, they do not have to try to two DMARDs in combination to meet medical necessity criteria). However, members with RA must still meet the two preferred self-administered (i.e., subcutaneous) biologic product requirement.

Approval duration: 6 months

Continuation of tocilizumab (Actemra) meets the definition of medical necessity when ALL of the following are met:

1. An authorization/reauthorization for tocilizumab has been previously approved by Florida Blue or another health plan in the past 2 years for the treatment of a condition in Table 1, OR the member previously met ALL indication-specific initiation criteria.

2. Member has demonstrated a beneficial response to treatment with tocilizumab

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

a. Abatacept (Orencia)

b. Adalimumab (Humira)

c. Anakinra (Kineret)

d. Apremilast (Otezla)

e. Certolizumab (Cimzia)

f. Etanercept (Enbrel)

g. Golimumab (Simponi)

h. Infliximab (Remicade)

i. Ixekizumab (Taltz)

j. Secukinumab (Cosentyx)

k. Tofacitinib (Xeljanz)

l. Ustekinumab (Stelara)

m. Vedolizumab (Entyvio)

4. The dosage does not exceed the following based on the specific indication:

a. RA: 8 mg/kg IV (max of 800 mg) every 4 weeks OR 162 mg SQ every week

b. SJIA/SJRA: 12 mg/kg IV every 2 weeks

c. PJIA/PJRA: 10 mg/kg IV every 4 weeks

d. Castleman's Disease: 12 mg/kg IV every 2 weeks

Approval duration: 1 year

Tocilizumab IV meets the definition of medical necessity when administered for treatment of the following Orphan Drug Indication when the dosage does not exceed 12 mg/kg IV every 2 weeks:

1. Systemic sclerosis

Approval duration: 1 year

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: tocilizumab is indicated for the treatment of the following conditions

• Rheumatoid arthritis (RA) in persons with moderately to severely active disease who have had an inadequate response to one or more DMARDs (IV or SQ formulation)

Giant cell arteritis (GCA) in adult patients (SQ ONLY)

• Polyarticular juvenile idiopathic arthritis (PJIA) in persons 2 years of age or older with active disease (IV ONLY)

• Systemic juvenile idiopathic arthritis (SJIA) in persons 2 years of age or older with active disease (IV ONLY)

For the treatment of RA, tocilizumab can be administered as an IV infusion drip over 1 hour or a subcutaneous injection. When administered intravenously, it should not be administered as an IV bolus or push. Initially, the subcutaneous injection should be administered under the guidance of a healthcare practitioner. After proper training, a member may self-inject tocilizumab or the member’s caregiver may administer tocilizumab if the healthcare practitioner determines that it is appropriate.

Therapy should not be initiated in persons with an absolute neutrophil count (ANC) less than 2000, platelet count less than 100,000, or an ALT/AST greater than 1.5 times the upper limit of normal (ULN). The recommended dosage, based on indication, is identified in Table 2. Tocilizumab may be used alone or in combination with methotrexate; in RA, other DMARDs may be used.

Table 2

FDA-approved indications and dosing

Indication

Dose

GCA

SQ injection

162 mg given once every week in combination with a tapering course of glucocorticoids. Every other week dosing may be prescribed based on clinical considerations.

RA

IV infusion

4 mg/kg every 4 weeks initially, followed by an increase to 8 mg/kg every 4 weeks based on clinical response.

SQ injection

Less than 100 kg

162 mg SQ every other week, followed by an increase to weekly based on clinical response

At or above 100 kg

162 mg SQ every week

PJIA

Less than 30 kg

10 mg/kg

30 kg or more

8 mg/kg

SJIA

Less than 30 kg

12 mg/kg

30 kg or more

8 mg/kg

RA, rheumatoid arthritis; PJIA, polyarticular juvenile idiopathic arthritis; SJIA, systemic juvenile idiopathic arthritis

Dosage Adjustments: Table 3 reviews recommended dose modifications for laboratory abnormalities associated with treatment of RA. Dose reduction of tocilizumab has not been studied in SJIA and PJIA populations. Dose interruptions are recommended for liver enzyme abnormalities, low neutrophil counts, and low platelet counts in persons with SJIA and PJIA at levels similar to what is outline for persons with RA.

Table 3

Dose Modifications

Laboratory Abnormality

Lab Value

Recommendation

Liver enzymes

Greater than 1 to 3x ULN

Dose modify concomitant DMARDs if appropriate.

For persistent increases in this range

• IV: reduce tocilizumab dose to 4 mg/kg or interrupt tocilizumab until ALT or AST have normalized

• SQ: reduce injection frequency to every other week or hold dosing until ALT/AST have normalized. Resume every other week and increase frequency to every week as clinically appropriate

Greater than 3 to 5x ULN

(confirmed by repeat testing)

Interrupt tocilizumab dosing until less than 3x ULN and follow recommendations above for greater than 1 to 3x ULN.

For persistent increases greater than 3x ULN, discontinue tocilizumab.

Greater than 5x ULN

Discontinue tocilizumab.

Low ANC

Greater than 1000

Maintain dose.

500-1000

Interrupt tocilizumab dosing. When ANC greater than 1000 cells per mm3:

• IV: resume tocilizumab at 4 mg/kg and increase to 8 mg/kg as clinically appropriate

• SQ: resume at every other week and increase frequency to every week as clinically appropriate

Less than 500

Discontinue tocilizumab.

Low platelet count

 

Interrupt tocilizumab dosing. When platelet count is greater than 100,000 cells per mm3:

• IV: resume tocilizumab at 4 mg/ kg and increase to 8 mg/kg as clinically appropriate

• SQ: resume at every other week and increase frequency to every week as clinically appropriate.

 

Less than 50,000

Discontinue tocilizumab.

ULN, upper limit of normal; DMARD, disease modifying anti-rheumatic drug; ANC, absolute neutrophile count

Drug Availability: tocilizumab is supplied in the following strengths as a single-use vial

IV Formulation

• 80 mg/4 mL

• 200 mg/10 mL

• 400 mg/20 mL

SQ Formulation

• 162 mg single-use prefilled glass syringe

PRECAUTIONS:

Boxed Warning

• Serious infections leading to hospitalization or death including tuberculosis (TB), bacterial, invasive fungal, viral, and other opportunistic infections have occurred in persons receiving tocilizumab.

• If a serious infection develops, interrupt tocilizumab until the infection is controlled.

• Perform test for latent TB; if positive, start treatment for TB prior to starting tocilizumab.

• Monitor all individuals administered tocilizumab for active TB during treatment, even if initial latent TB test is negative.

Contraindication

Do not administer to persons with a history of hypersensitivity to tocilizumab.

Warnings

Gastrointestinal perforation: use with caution in persons who may be at an increased risk.

Laboratory monitoring: recommended due to potential consequences of treatment-related changes in neutrophils, platelets, lipids, and liver function tests.

Live vaccines: do not administer with tocilizumab.

BILLING/CODING INFORMATION:

HCPCS Coding:

J3262

Injection, tocilizumab, 1 mg [for intravenous formulation]

J3590

Unclassified biologics [for subcutaneus formulation]

ICD-10 Diagnoses Codes That Support Medical Necessity for J3262:

D47.Z2

Castleman disease

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

M06.20 – M06.29

Rheumatoid bursitis

M06.30 – M06.39

Rheumatoid nodule

M06.80 – M06.89

Other specified rheumatoid arthritis

M06.9

Rheumatoid arthritis, unspecified

M08.09

Unspecified juvenile rheumatoid, multiple sites

M08.20 – M08.29

Juvenile rheumatoid arthritis with systemic onset

M08.3

Juvenile rheumatoid polyarthritis (seronegative)

M08.89

Other juvenile arthritis, multiple sites

M34.0 – M34.9

Systemic sclerosis [scleroderma]

ICD-10 Diagnoses Codes That Support Medical Necessity for J3590:

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

M06.20 – M06.29

Rheumatoid bursitis

M06.30 – M06.39

Rheumatoid nodule

M06.80 – M06.89

Other specified rheumatoid arthritis

M06.9

Rheumatoid arthritis, unspecified

M31.5

Giant cell arteritis with polymyalgia rheumatica

M31.6

Other giant cell arteritis

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:

B cells: lymphocytes that play a large role in the humoral immune response (as opposed to the cell-mediated immune response, which is governed by T cells). The principal functions of B cells are to make antibodies against antigens, perform the role of antigen-presenting cells (APCs) and eventually develop into memory B cells after activation by antigen interaction. B cells are an essential component of the adaptive immune system.

Cytokines: any of a number of substances that are secreted by specific cells of the immune system which carry signals locally between cells, and thus have an effect on other cells.

DMARDs: An acronym for disease-modifying antirheumatic drugs.

Fibroblast: a type of cell that synthesizes the extracellular matrix and collagen, the structural framework (stroma) for animal tissues, and plays a critical role in wound healing.

Interleukin-6 (IL-6): a protein that in humans is encoded by the IL6 gene. It acts as both a pro-inflammatory and anti-inflammatory cytokine. It is secreted by T cells and macrophages to stimulate immune response to trauma, especially burns or other tissue damage leading to inflammation.

Lymphocyte: a type of white blood cell in the vertebrate immune system.

Macrophages: white blood cells within tissues, produced by the division of monocytes.

Monocyte: a type of white blood cell, part of the human body’s immune system.

Rheumatoid arthritis: usually strikes between ages 20 and 50. Inflammation begins in a joint, usually those of the fingers and hands, resulting in pain, swelling, redness, and eventually joint deformity. It is considered an autoimmune disease, which can affect the entire body, causing fatigue, weight loss, weakness, fever, and loss of appetite. It affects each person differently, with symptoms ranging from mild to debilitating. In many cases, it is difficult to control. In about one in six cases, rheumatoid arthritis becomes severely debilitating and can shorten the life of the person affected.

T cells or T lymphocytes: belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity.

RELATED GUIDELINES:

Abatacept (Orencia®), 09-J0000-67

Adalimumab (Humira®), 09-J0000-46

Anakinra (Kineret®), 09-J0000-45

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

Etanercept (Enbrel®), 09-J0000-38

Golimumab (Simponi®, Simponi® Aria™), 09-J1000-11

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

Rituximab (Rituxan®), 09-J0000-59

Tofacitinib (Xeljanz) Tablets, 09-J1000-86

OTHER:

Table 3:

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. Actemra (tocilizumab) [package insert]. Genetech, Inc. South San Francisco (CA): May 2017.
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  3. Beukelman T, Patkar NM, Saag KG, et al. 2011 American College of Rheumatology recommendations for the treatment of juvenile idiopathic arthritis: initiation and safety monitoring of therapeutic agents for the treatment of arthritis and systemic features. Arthritis Care Rese 2011;63(4):465-82.
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  6. 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.
  7. 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.
  8. 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.
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  13. Nishimoto N, Miyasaka N, Yamamoto K, et al. Study of active controlled tocilizumab monotherapy for rheumatoid arthritis patients with an inadequate response to methotrexate (SATORI): significant reduction in disease activity and serum vascular endothelial growth factor by IL-6 receptor inhibition therapy. Mod Rheumatol. 2009;19(1):12-19.
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COMMITTEE APPROVAL:

This Medical Coverage Guideline (MCG) was approved by the BCBSF Pharmacy Committee on 06/14/17.

GUIDELINE UPDATE INFORMATION:

05/15/10

New Medical Coverage Guideline.

01/01/11

Revision to guideline; consisting of updating coding.

07/15/11

Review and revision to guideline; consisting of adding new indication of SJIA, updating dosing, coding and references.

07/15/12

Review and revision to guideline; consisting of reformatting position statement, dosage and administration, precautions and references.

01/15/13

Revision to guideline; consisting of modifying coverage criteria for rheumatoid arthritis.

09/15/13

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

01/01/14

Revision to guideline; consisting of updating position statement and adding new formulation.

04/15/14

Revision to guideline; consisting of revising position statement.

09/15/14

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

09/15/15

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

11/01/15

Revision: ICD-9 Codes deleted.

09/15/16

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

10/01/16

Revision: ICD-10 code updates.

05/15/17

Revision to guideline consisting of clarifying language in the description section and position statement.

07/15/17

Revision to guideline consisting of updating the position statement, dosage/administration section, coding/billing, and references to include a new FDA-approved indication of giant cell arteritis (GCA).

Date Printed: August 22, 2017: 06:56 AM