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09-J2000-88

Original Effective Date: 09/15/17

Reviewed: 08/09/17

Revised: 00/00/00

Next Review: 09/12/18

Subject: Sarilumab (Kevzara) 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.

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

DESCRIPTION:

Sarilumab (Kevzara) is an injectable human monoclonal antibody that binds specifically to both soluble and membrane-bound interleukin-6 (IL-6) receptors. The IL-6 receptor plays a major role in regulating the underlying disease pathophysiology and clinical manifestations of rheumatoid arthritis (RA). In patients with RA, elevated levels of IL-6 in serum and synovial fluid are closely associated with synovitis, systemic inflammation, bone metabolism, fatigue, and joint destruction. Sarilumab was approved by the US Food and Drug Administration (FDA) in May 2017 for “treatment of adult patients with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs (DMARDs).” Sarilumab is the second anti-IL-6 agent to be approved by the FDA for the treatment of RA. Tocilizumab (Actemra) was the first anti-IL-6 agent to be approved by the FDA for RA in January 2010. Siltuximab (Sylvant) is also an anti-IL-6 agent but works by binding to IL-6 itself as opposed to the IL-6 receptor. Siltuximab is FDA-approved for the treatment of multicentric Castleman disease only.

The safety and efficacy of sarilumab leading to FDA-approval was assessed in two randomized, double-blind, placebo-controlled multicenter studies (MOBILITY and TARGET) in patients older than 18 years with moderately to severely active RA. Patients had at least 8 tender and 6 swollen joints at baseline. The MOBILITY study evaluated 1,197 patients with moderately to severely active RA who had inadequate clinical response to methotrexate (MTX). Patients received subcutaneous sarilumab 200 mg, sarilumab 150 mg, or placebo every two weeks with concomitant MTX. After Week 16, patients with an inadequate response could have been rescued with sarilumab 200 mg every two weeks. The TARGET study evaluated 546 patients with moderately to severely active rheumatoid arthritis who had an inadequate clinical response or were intolerant to one or more TNF-alpha antagonists. Patients received subcutaneous sarilumab 200 mg, sarilumab 150 mg, or placebo every two weeks with concomitant conventional DMARDs (MTX, sulfasalazine, leflunomide, and/or hydroxychloroquine). After Week 12, patients with an inadequate response could have been rescued with sarilumab 200 mg every two weeks. In both studies, the primary endpoint was the proportion of patients who achieved an ACR20 response at Week 24. Other key endpoints evaluated included ACR 50, ACR70, and Disease Activity Score 28-C-Reactive Protein (DAS28-CRP) <2.6. In both studies, patients treated with either 200 mg or 150 mg of sarilumab every two weeks + MTX/DMARD had higher ACR20, ACR50, and ACR70 response at various time points. A summary of the results are seen in Table 1.

Table 1: Clinical Response Results from MOBILITY and TARGET Studies

 

MOBILITY

TARGET

 

Placebo (n=398)

Sarilumab
150 mg (n=400)

Sarilumab 200 mg

(n=399)

Placebo

(n=181)

Sarilumab 150 mg

(n=181)

Sarilumab 200 mg

(n=184)

ACR20

 

Week 12

34.7%

54.0%

64.9%

37.6%

54.1%

62.5%

Week 24

33.4%

58.0%

66.4%

33.7%

55.8%

60.9%

Week 52

31.7%

53.5%

58.6%

-

-

-

ACR50

 

Week 12

12.3%

26.5%

36.3%

13.3%

30.4%

33.2%

Week 24

16.6%

37.0%

45.6%

18.2%

37.0%

40.8%

Week 52

18.1%

40.0%

42.9%

-

-

-

ACR70

 

Week 12

4.0%

11.0%

17.5%

2.2%

13.8%

14.7%

Week 24

7.3%

19.8%

24.8%

7.2%

19.9%

16.3%

Week 52

9.0%

24.8%

26.8%

-

-

-

DAS28-CRP < 2.6

 

Week 12

4.8%

18.0%

23.1%

3.9%

17.1%

17.9%

Week 24

10.1%

27.8%

34.1%

7.2%

24.9%

28.8%

The American College of Rheumatology (ACR) guidelines for treatment of RA was last updated in 2015. Sarilumab is not included in the guidelines as it was approved after publication. However, sarilumab has the same mechanism of action (i.e., IL-6 inhibition) and adverse effect profile as tocilizumab (Actemra). The RA guidelines support the use of a non-TNF biologic 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 not include a non-TNFi biologic, 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 FDA 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: adalimumab (Humira), etanercept (Enbrel), and golimumab (Simponi) are the preferred self-administered biologic products for rheumatoid arthritis (RA)

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

1. Sarilumab will be used for the treatment of an indication listed in Table 2, and ALL indication-specific criteria are met

2. The member is 18 years of age or older

3. Sarilumab will NOT be administered in combination with ANY of the following:

a. abatacept (Orencia)

b. adalimumab (Humira)

c. anakinra (Kineret)

d. apremilast (Otezla)

e. brodalumab (Siliq)

f. certolizumab (Cimzia)

g. etanercept (Enbrel)

h. golimumab (Simponi, Simponi Aria)

i. guselkumab (Tremfya)

j. infliximab products (Remicade, Inflectra, Renflexis)

k. ixekizumab (Taltz)

l. secukinumab (Cosentyx)

m. tocilizumab (Actemra)

n. tofacitinib (Xeljanz, Xeljanz XR)

o. ustekinumab (Stelara)

p. vedolizumab (Entyvio)

Table 2

Indications and Specific Criteria

Indication

Criteria

Maximum Allowable Dosage

Rheumatoid arthritis (RA)

When ALL of the following are met (“1”, “2”, “3”, and “4”):

1. Member’s disease is moderately to severely active

2. Member does not have any of the following baseline lab abnormalities:

a. ANC less than 2,000/mm3

b. Platelet count less than 150,000/mm3

c. ALT or AST greater than 1.5-times ULN

3. 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)*

4. 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):

i. adalimumab (Humira)

ii. etanercept (Enbrel)

iii. golimumab (Simponi)

b. Alternatives to the use of an anti-TNF biologic should be considered due to a product warning and/or precaution for EITHER of the following (the specific condition must be provided):

i. Current or worsening congestive heart failure

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

• 200 mg every 2 weeks

Approval duration: 16 weeks

 

ANC: absolute neutrophil count, ALT: alanine aminotransferase, AST: aspartate aminotransferase, ULN: upper limit of normal, DMARD: disease modifying anti-rheumatic drug

*NOTE: if the member has had an inadequate response to previous biologic therapy, other than sarilumab, that is FDA-approved for the requested indication listed in Table 2, the member is NOT required to have had an inadequate therapeutic response to additional non-biologic prerequisite therapy (e.g., for rheumatoid arthritis, if member has previously had an inadequate response to adalimumab, but does not have a history of inadequate response to methotrexate, they do not have to try methotrexate to meet medical necessity criteria)

Continuation of sarilumab (Kevzara) meets the definition of medical necessity when ALL of the following criteria are met:

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

2. Member does NOT currently have any of the following lab abnormalities as assessed during sarilumab treatment:

a. ANC less than 500/mm3

b. Platelet count less than 50,000/mm3

c. ALT greater than 5-times ULN

3. Member has demonstrated a beneficial response to therapy with sarilumab

4. Sarilumab will NOT be administered in combination with ANY of the following:

a. abatacept (Orencia)

b. adalimumab (Humira)

c. anakinra (Kineret)

d. apremilast (Otezla)

e. brodalumab (Siliq)

f. certolizumab (Cimzia)

g. etanercept (Enbrel)

h. golimumab (Simponi, Simponi Aria)

i. guselkumab (Tremfya)

j. infliximab products (Remicade, Inflectra, Renflexis)

k. ixekizumab (Taltz)

l. secukinumab (Cosentyx)

m. tocilizumab (Actemra)

n. tofacitinib (Xeljanz, Xeljanz XR)

o. ustekinumab (Stelara)

p. vedolizumab (Entyvio)

5. The dosage of sarilumab does not exceed 200 mg every 2 weeks

Approval duration: 12 months

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

• Treatment of adult patients with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs (DMARDs)

• The recommended dosage of is 200 mg once every two weeks given as a subcutaneous injection. Reduce dose to 150 mg once every two weeks for management of neutropenia, thrombocytopenia and elevated liver enzymes. Sarilumab may be used as monotherapy or in combination with methotrexate (MTX) or other conventional DMARDs. Prior to initiating. test patients for latent tuberculosis. A patient may self-inject after proper training on preparation and administration. The pre-filled syringe should sit at room temperature for 30 minutes prior to injection. Rotate injection sites with each injection.

• Sarilumab initiation is NOT recommended in patients with an absolute neutrophil count (ANC) less than 2,000/mm3, platelet count less than 150,000/ mm3, or who have ALT or AST above 1.5 times the upper limit of normal (ULN).

• Avoid using sarilumab with biological DMARDs because of the possibility of increased immunosuppression and increased risk of infection.

Dose Adjustments

• Low Absolute Neutrophil Count (ANC)

o ANC greater than 1,000/mm3 – maintain current dosage

o ANC 500 to 1,000/mm3 - hold treatment until ANC greater than 1,000/mm3. Resume at 150 mg every two weeks and increased to 200 mg every two weeks as clinically appropriate.

o ANC less than 500/mm3 - discontinue

• Low Platelet Count

o 50,000–100,000/mm3 – hold treatment until platelets greater than 100,000/mm3. Resume at 150 mg every two weeks and increased to 200 mg every two weeks as clinically appropriate.

o Less than 50,000/mm3 – discontinue if confirmed by repeat testing

• Liver Enzyme Abnormalities

o ALT greater than ULN to 3 times ULN or less – consider dosage modification of concomitant DMARDs as clinically appropriate.

o ALT greater than 3 times ULN to 5 times ULN or less – hold treatment until ALT less than 3 times ULN. Resume at 150 mg every two weeks and increased to 200 mg every two weeks as clinically appropriate.

o ALT greater than 5 times ULN - discontinue

Drug Availability

• 150 mg/1.14 mL and 200 mg/1.14 mL single-dose pre-filled syringes that come in a package of two syringes

• Refrigerate at 36°F to 46°F (2°C to 8°C) in original carton to protect from light. If needed, sarilumab may be stored at room temperature up to 77°F (25°C) up to 14 days in the outer carton.

PRECAUTIONS:

Boxed Warning

• WARNING: RISK OF SERIOUS INFECTIONS

o Patients treated with Kevzara are at increased risk for developing serious infections that may lead to hospitalization or death. Opportunistic infections have also been reported in patients receiving Kevzara. Most patients who developed infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids.

o Avoid use of Kevzara in patients with an active infection.

o Reported infections include:

- Active tuberculosis, which may present with pulmonary or extrapulmonary disease. Patients should be tested for latent tuberculosis before Kevzara use and during therapy. Treatment for latent infection should be initiated prior to Kevzara use.

- Invasive fungal infections, such as candidiasis, and pneumocystis. Patients with invasive fungal infections may present with disseminated, rather than localized, disease.

- Bacterial, viral and other infections due to opportunistic pathogens.

o Closely monitor patients for signs and symptoms of infection during treatment with Kevzara. If a serious infection develops, interrupt Kevzara until the infection is controlled.

o Consider the risks and benefits of treatment with Kevzara prior to initiating therapy in patients with chronic or recurrent infection.

Contraindications

• Patients with known hypersensitivity to sarilumab or any of the inactive ingredients

Precautions/Warnings

Serious Infections: Serious and sometimes fatal infections due to bacterial, mycobacterial, invasive fungal, viral, or other opportunistic pathogens have been reported in patients receiving immunosuppressive agents including sarilumab for RA. The most frequently observed serious infections with sarilumab included pneumonia and cellulitis. Avoid sarilumab use in patients with an active infection, including localized infections.

o Tuberculosis: Evaluate patients for TB risk factors and test for latent infection prior to initiating treatment. Treat patients with latent TB with standard antimycobacterial therapy before initiating sarilumab

o Viral Reactivation: Viral reactivation has been reported with immunosuppressive biologic therapies. Cases of herpes zoster were observed in clinical studies with sarilumab. The risk of Hepatitis B reactivation with is unknown since patients who were at risk for reactivation were excluded.

Laboratory Abnormalities

o Neutropenia: Treatment with sarilumab was associated with a higher incidence of decrease in absolute neutrophil count (ANC). Assess neutrophil count prior to initiation of therapy and monitor neutrophil count 4 to 8 weeks after start of therapy and every 3 months thereafter. Adjust the dose as needed based on ANC results.

o Thrombocytopenia: Treatment with sarilumab was associated with a reduction in platelet counts in clinical studies. Assess platelet count prior to initiation of therapy and monitor platelets 4 to 8 weeks after start of therapy and every 3 months thereafter. Adjust the dose as needed based on platelet counts.

o Elevated Liver Enzymes: Treatment with sarilumab was associated with a higher incidence of transaminase elevations. These elevations were transient and did not result in any clinically evident hepatic injury in clinical studies. Increased frequency and magnitude of these elevations were observed when potentially hepatotoxic drugs (e.g., MTX) were used in combination. Assess ALT/AST levels prior to initiation of treatment and monitor ALT and AST levels 4 to 8 weeks after start of therapy and every 3 months thereafter. Adjust the dose as needed based on transaminase elevations.

o Lipid Abnormalities: Treatment with sarilumab was associated with increases in lipid parameters such as LDL-C, HDL-C, and/or triglycerides. Assess lipid parameters approximately 4 to 8 weeks following initiation of treatment, then at approximately 6 month intervals. Manage patients according to clinical guidelines for the management of hyperlipidemia.

Gastrointestinal (GI) Perforation: Gastrointestinal perforations have been reported in clinical studies. Risk may be increased with concurrent diverticulitis or concomitant use of NSAIDs or corticosteroids. Promptly evaluate acute abdominal signs or symptoms.

• Immunosuppression: Treatment with immunosuppressants may result in an increased risk of malignancies. The impact of treatment with sarilumab on the development of malignancies is not known but malignancies were reported in clinical studies.

Hypersensitivity reactions: Hypersensitivity reactions have been reported in association with sarilumab. Injection site rash, rash, and urticaria were the most frequent hypersensitivity reactions.

• Active Hepatic Disease and Hepatic Impairment: Treatment with sarilumab is not recommended in patients with active hepatic disease or hepatic impairment, as treatment was associated with transaminase elevations.

Live vaccines: Avoid concurrent use of live vaccines during treatment with sarilumab due to the risk of infection. Follow vaccination guidelines.

BILLING/CODING INFORMATION:

The following codes may be used to describe:

HCPCS Coding

C9399

Unclassified drugs or biologicals (Hospital outpatient use ONLY)

J3590

Unclassified biologics

ICD-10 Diagnoses Codes That Support Medical Necessity

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

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

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

DEFINITIONS:

DMARDs: An acronym for disease-modifying antirheumatic drugs.

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.

Rheumatoid arthritis: usually occurs 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.

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 Products, 09-J0000-39

Rituximab (Rituxan), 09-J0000-59

Tocilizumab (Actemra), 09-J1000-21

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. Burmester GR, Lin Y, Patel R, et al. Efficacy and safety of sarilumab monotherapy versus adalimumab monotherapy for the treatment of patients with active rheumatoid arthritis (MONARCH): a randomised, double-blind, parallel-group phase III trial. Ann Rheum Dis. 2017 May;76(5):840-847.
  2. Clinical Pharmacology [database online]. Tampa, FL: Gold Standard, Inc.; 2017. Available at: www.clinicalpharmacilogy-ip.com. Accessed 7/17/17.
  3. Fleischmann R, van Adelsberg J, Lin Y, et al. Sarilumab and Nonbiologic Disease-Modifying Antirheumatic Drugs in Patients With Active Rheumatoid Arthritis and Inadequate Response or Intolerance to Tumor Necrosis Factor Inhibitors. Arthritis Rheumatol. 2017 Feb;69(2):277-290.
  4. Genovese MC , Fleischmann R , Kivitz AJ , et al: Sarilumab plus methotrexate in patients with active rheumatoid arthritis and inadequate response to methotrexate: results of a phase III study. Arthritis Rheumatol 2015; 67(6):1424-1437.
  5. 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.
  6. 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.
  7. Kevzara (sarilumab) package insert. Bridgewater, NJ: Sanofi-Aventis US. LLC; 2017 May.
  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.
  9. Micromedex Healthcare Series [Internet Database]. Greenwood Village, Colo: Thomson Healthcare. Updated periodically. Accessed 7/17/17.
  10. 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.
  11. 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.
  12. 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.
  13. Smolen JS, Landewé R, Bijlsma J, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis. 2017 Jun;76(6):960-977.
  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 08/09/17.

GUIDELINE UPDATE INFORMATION:

09/15/17

New Medical Coverage Guideline.

Date Printed: December 16, 2017: 09:27 PM