BCBSNJ Medical Policy for - (Drugs) Policy Number

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Horizon BCBSNJ
Uniform Medical Policy Manual	Section:	Drugs
	Policy Number:	076
	Effective Date:	09/11/2020

	Original Policy Date:	02/23/2010
	Last Review Date:	09/08/2020
	Date Published to Web:	03/17/2010

Subject:
Tocilizumab (Actemra)

Description:
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IMPORTANT NOTE:

The purpose of this policy is to provide general information applicable to the administration of health benefits that Horizon Blue Cross Blue Shield of New Jersey and Horizon Healthcare of New Jersey, Inc. (collectively “Horizon BCBSNJ”) insures or administers. If the member’s contract benefits differ from the medical policy, the contract prevails. Although a service, supply or procedure may be medically necessary, it may be subject to limitations and/or exclusions under a member’s benefit plan. If a service, supply or procedure is not covered and the member proceeds to obtain the service, supply or procedure, the member may be responsible for the cost. Decisions regarding treatment and treatment plans are the responsibility of the physician. This policy is not intended to direct the course of clinical care a physician provides to a member, and it does not replace a physician’s independent professional clinical judgment or duty to exercise special knowledge and skill in the treatment of Horizon BCBSNJ members. Horizon BCBSNJ is not responsible for, does not provide, and does not hold itself out as a provider of medical care. The physician remains responsible for the quality and type of health care services provided to a Horizon BCBSNJ member.

Horizon BCBSNJ medical policies do not constitute medical advice, authorization, certification, approval, explanation of benefits, offer of coverage, contract or guarantee of payment.
__________________________________________________________________________________________________________________________

Tocilizumab (Actemra®) is an interleukin-6 (IL-6) receptor inhibitor that has been approved by the Food and Drug Administration (FDA) for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response to one or more tumor necrosis factor (TNF) antagonist therapies. Tocilizumab is available as a solution for dilution and intravenous administration by a healthcare professional. Tocilizumab is also available as a prefilled syringe for self-administered subcutaneous administration.

IL-6 is a pro-inflammatory cytokine produced by various cells, including T- and B-cells, lymphocytes, monocytes, and fibroblasts. It plays a role in several physiological processes, including T-cell activation, induction of immunoglobulin secretion, initiation of hepatic acute phase protein synthesis, and stimulation of hematopoietic precursor cell proliferation and differentiation. Additionally, IL-6 is produced by synovial and endothelial present in joints. Thus, overproduction of IL-6 in inflammatory processes such as RA causes symptoms associated with this disease. By blocking IL-6 receptors, tocilizumab works to diminish these processes and reduce RA symptomatology.

The results of the LITHE trial showed that tocilizumab inhibits the progression of structural damage, induces major clinical response, and improves physical function when used as treatment for rheumatoid arthritis in conjunction with methotrexate when compared to methotrexate alone.

In October 2012 the FDA expanded the approved indication for tocilizumab for the treatment of adults with moderately to severely active rheumatoid arthritis who have had inadequate response to one or more disease-modifying anti-rheumatic drugs (DMARDs). Tocilizumab can be used both alone as a single-agent therapy and in combination with methotrexate or other DMARDs. The FDA approval of this expanded indication is based on three pivotal phase three studies: TOWARD, OPTION, and LITHE. The TOWARD trial examined the efficacy and safety of tocilizumab combined with DMARDs in patients with active rheumatoid arthritis compared to DMARDs plus placebo. At week 24, the proportion of patients achieving response according to the American College of Rheumatology for 20% improvement was significantly greater in the tocilizumab plus DMARD group than in the control group (p <0.0001).The OPTION trial investigated the effects of tocilizumab added to a stable dosage of methotrexate on biochemical markers of bone and cartilage metabolism. At week 24, tocilizumab combined with methotrexate was found to reduce systemic bone resorption, cartilage turnover, and proteolytic enzyme MMP-3 levels more profoundly than the methotrexate plus placebo group (p<.01). The LITHE trial assessed the efficacy and safety of tocilizumab plus methotrexate versus methotrexate alone in preventing structural joint damage and improving physical function and disease activity in patients with moderate-to-severe rheumatoid arthritis. Tocilizumab plus methotrexate resulted in greater inhibition of joint damage and improvement in physical function than methotrexate alone (p<0.0001).

In April 2013 the FDA expanded the approved indication for tocilizumab to include the treatment of patients 2 years of age and older with active polyarticular juvenile idiopathic arthritis (PJIA). The efficacy of tocilizumab was assessed in a three-part study including an open-label extension in children 2 to 17 years of age with active PJIA, who had an inadequate response to methotrexate or inability to tolerate methotrexate. Patients had at least 6 months of active disease (mean disease duration of 4.2 ± 3.7 years), with at least five joints with active arthritis (swollen or limitation of movement accompanied by pain and/or tenderness) and/or at least 3 active joints having limitation of motion (mean, 20 ± 14 active joints). The patients treated had subtypes of JIA that at disease onset included Rheumatoid Factor Positive or Negative Polyarticular JIA, or Extended Oligoarticular JIA. Treatment with a Part I consisted of a 16-week active tocilizumab treatment lead-in period (n=188) followed by Part II, a 24-week randomized double-blind placebo-controlled withdrawal period, followed by Part III, a 64-week open-label period. Eligible patients weighing at or above 30 kg received tocilizumab at 8 mg/kg IV once every four weeks. Patients weighing less than 30 kg were randomized 1:1 to receive either tocilizumab 8 mg/kg or 10 mg/kg IV every four weeks. At the conclusion of the open-label Part I, 91% of patients taking background MTX in addition to tocilizumab and 83% of patients on tocilizumab monotherapy achieved an ACR 30 response at week 16 compared to baseline and entered the blinded withdrawal period (Part II) of the study. The proportions of patients with JIA ACR 50/70 responses in Part I were 84.0%, and 64%, respectively for patients taking background MTX in addition to tocilizumab and 80% and 55% respectively for patients on tocilizumab monotherapy. In Part II, patients (ITT, n=163) were randomized to tocilizumab (same dose received in Part I) or placebo in a 1:1 ratio that was stratified by concurrent methotrexate use and concurrent corticosteroid use. Each patient continued in Part II of the study until Week 40 or until the patient satisfied JIA ACR 30 flare criteria (relative to Week 16) and qualified for escape. The primary endpoint was the proportion of patients with a JIA ACR 30 flare at week 40 relative to week 16. JIA ACR 30 flare was defined as 3 or more of the 6 core outcome variables worsening by at least 30% with no more than 1 of the remaining variables improving by more than 30% relative to Week 16. Tocilizumab treated patients experienced significantly fewer disease flares compared to placebo-treated patients (26% [21/82] versus 48% [39/81]; adjusted difference in proportions -21%, 95% CI: -35%, -8%). During the withdrawal phase (Part II), more patients treated with tocilizumab showed JIA ACR 30/50/70 responses at Week 40 compared to patients withdrawn to placebo.

In October 2013, the FDA approved the subcutaneous formulation of tocilizumab for the treatment of adults with moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more DMARDs. The FDA approval of this formulation is based on two Phase 3 double-blind, controlled, multicenter studies, with a total of 1,751 patients with active RA. Study 1 was a non-inferiority study that compared the efficacy and safety of tocilizumab 162 mg subcutaneously every week + DMARD versus tocilizumab 9 mg/kg intravenously every 4 weeks + DMARD. Results demonstrated the percentage of patients achieving ACR20, ACR50, and ACR70 responses at 24 weeks were comparable for patients in both treatment arms, percentage of patients with ACR20 taking tocilizumab subcutaneous 69.4% (95% CI 65.5 to 73.2) and tocilizumab intravenous 73.4% (95% CI 69.6 to 77.1). Study 2 was a placebo-controlled, superiority study that demonstrated significantly higher ACR20, ACR50, and ACR70 scores at 24 weeks as compared with placebo, percentage of patients with ACR20 taking tocilizumab subcutaneous 60.9% (95% CI 56.3 to 65.4) and placebo subcutaneous 31.5% (95% CI 25.4 to 37.7). The safety profile of tocilizumab subcutaneous was consistent with its intravenous formulation with the exception of injection site reactions, 10.1% and 2.4% in study 1 and 7.1% versus 4.1% in study 2.

The efficacy and safety of subcutaneously administered tocilizumab was assessed in a single, randomized double-blind, multicenter study in patients with active Giant Cell Arteritis. In the study, 251 screen patients with new-onset of relapsing Giant Cell Arteritis were randomized to one of four treatments arms. Two SC doses of tocilizumab were compared to two different placebo control groups randomized 2:1:1:1. The study consisted of a 52-week blinded period, followed by a 104-week open –label extension. All patients received background glucocorticoid (prednisone) therapy. Each of the tocilizumab -treated group and one of the placebo-treated group followed by a pre specified prednisone-taper regimen with the aim to reach 0 mg by 26 weeks, while the second placebo-treated group followed a pre-specified prednisone-taper regimen with the aim to reach 0 mg by 52 weeks designed to be more in keeping with standard practice. The primary efficacy endpoint was the proportion of patients achieving sustained remission from Week 12 through 52. tocilizumab 162 mg weekly and 162 mg every other week plus 26 weeks prednisone taper both showed superiority in achieving sustained remission from week 12 through week 52 compared with placebo plus 26 week prednisone taper. Both tocilizumab treatment arms also showed superiority compared to the placebo plus 52 weeks prednisone taper.

[INFORMATIONAL NOTE: The FDA-approved tocilizumab package insert has the following BLACK BOX WARNING: Risk of serious infections:
Patients treated with tocilizumab 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.

If a patient develops a serious infection, tocilizumab should be interrupted until the infection is controlled.

Reported infections include:

Active tuberculosis, which may present with pulmonary or extrapulmonary disease. Patients should be tested for latent tuberculosis before tocilizumab use and during therapy. Treatment for latent infection should be initiated prior to tocilizumab use.
Invasive fungal infections, including candidiasis, aspergillosis, and pneumocystis. Patients with invasive fungal infections may present with disseminated, rather than localized, disease.
Bacterial, viral, and other infections due to opportunistic pathogens.

The risks and benefits of treatment with tocilizumab 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 tocilizumab, including the possible development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy.

In April 2011, the FDA labeling added warnings and precautions regarding: gastrointestinal perforation (primarily as a complication of diverticulitis); changes in laboratory parameters (neutrophils, platelets, liver function tests, lipids); preexisting or recent onset demyelinating disorders; live vaccines, which should not be given concurrently.]

Policy:
(NOTE: For Medicare Advantage, please refer to the Medicare Coverage Section below for coverage guidance)

The requirements of the Horizon BCBSNJ Tocilizumab (Actemra) Program may require a precertification/prior authorization via MagellanRx Management. These requirements are member-specific: please verify member eligibility and requirements through the Horizon Provider Portal (www.horizonblue.com/provider). Ordering clinicians should request pre-certification from MagellanRx Management at ih.magellanrx.com or call 1-800-424-4508 (when applicable).

I. Please refer to a separate policy on Site of Administration for Infusion and Injectable Prescription Medications (Policy #142) under the Drug Section.

II. Prior to initiation of tocilizumab (Actemra®) members must meet ALL of the following criteria:

Member has been tested for latent tuberculosis (TB) AND if positive the patient has begun therapy for latent TB; AND
Member is not on concurrent treatment with another TNF-inhibitor, biologic response modifier or other non-biologic agent (i.e., apremilast, tofacitinib, baricitinib); AND
The prescriber is a specialist in the area of the patient’s diagnosis (e.g. rheumatologist) or has consulted with a specialist in the area of the patient’s diagnosis; AND
If a subcutaneous form of the drug is requested, the requested drug will be administered in an office/outpatient setting by a healthcare professional or home infusion by a home-health nurse and is there is documentation that member will not be self-administering. Documentation must be provided stating the member is unable to self-administer due to one of the following reasons:

III. Intravenous and subcutaneous tocilizumab (Actemra®) are considered medically necessary for the FDA approved indications in patients with active systemic juvenile idiopathic arthritis (SJIA) when ALL of the following criteria are met:

Member is 2 years of age or older
Member meets one of the following:

IV. Intravenous and subcutaneous tocilizumab (Actemra®) are considered medically necessary for the FDA approved indications in patients with active polyarticular juvenile idiopathic arthritis (PJIA) when ALL of the following criteria are met:

Member is 2 years of age or older; AND
Member meets one of the following:

IV. Intravenous and subcutaneous tocilizumab (Actemra®) are considered medically necessary for the FDA approved indication in adults with moderately-to-severely- active rheumatoid arthritis when the following criteria is met:

[

INFORMATIONAL NOTE

: The ACR 201

recommendations on use of biological DMARDs in RA patients are based on duration, severity and prior exposure to non-biologic DMARDs.

In order to assess if a patient is a candidate for biologic DMARD therapy, RA disease activity should be measured as per the tests below:

Table 2. Disease activity cutoffs for each American College of Rheumatology-recommended disease activity measure*
*Disease activity measure*	*Scale*	*Remission*	*Low/Minimal*	*Moderate*	*High/severe*
Patient-driven composite tools
PAS	0-10	0.00-0.25	0.26-3.70	3.71 to <8.0	8.00-10.00
PAS-II	0-10	0.00-0.25	0.26-3.70	3.71 to <8.0	8.00-10.00
RAPID-3	0-10	0-1.0	>1.0 to 2.0	>2.0 to 4.0	>4.0 to 10
Patient and provider composite tool
CDAI	0-76	≤2.8	>2.8 to 10.0	>10.0 to 22.0	>22.0
Patient, provider, and laboratory composite tools
DAS28 (ESR or CRP)	0-9.4	<2.6	≥2.6 to <3.2	≥3.2 to ≤5.1	>5.1
SDAI	0-86	≤3.3	>3.3 to ≤11.0	>11.0 to ≤26	>26
*PAS= Patient Activity Scale; RAPID-3= Routine Assessment of Patient Index Data with 3 measures; CDAI= Clinical Disease Activity Index; DAS28= Disease Activity Score with 28-joint counts; ESR= erythrocyte sedimentation rate; CRP= C-reactive protein; SDAI= Simplified Disease Activity Index

Algorithm 1 - Once RA disease severity has been measured, they can be stratified in different treatments algorithms depending on the duration of the disease:

Patients with Early RA (disease duration <6 months)
- Low disease activity or remission
  - DMARD monotherapy is recommended
- Moderate to high disease activity
  - DMARD monotherapy is recommended for those who are DMARD-naïve
  - If there is continued disease activity with DMARD therapy, consider combination of traditional DMARDs and TNF inhibitor or non TNF biologics
Patients with established RA (disease duration ≥6 months or meeting the 1987 ACR RA classification criteria)
- 1987 ACR RA classification criteria:
  - Morning stiffness
  - Arthritis of 3 or more joint areas
  - Arthritis of hand joints
  - Symmetric arthritis
  - Rheumatoid nodules
  - Serum rheumatoid factor
  - Radiographic changes
- Consider DMARD monotherapy for all patients of low, moderate, or high disease activity who are DMARD-naïve
- For patients who do not respond adequately on DMARD monotherapy, consider combination therapy of traditional DMARD, or TNF inhibitor without or without MTX, or non TNF biologic without or without MTX, or tafacitinib with or without MTX
- If patients continue to have moderate or high disease activity, consider switching to a different agent within the drug class of TNF inhibitors, or non-TNF biologics (with or without MTX), or tofacitinib with or without MTX. ]

VI. Intravenous tocilizumab (Actemra®) is considered medically necessary for the FDA approved indication in patients for the treatment of chimeric antigen receptor (CAR) T cell-induced severe or life-threatening cytokine release syndrome (CRS) when the following criteria are met:

Patient is 2 years or older; AND
Patient has received or will be receiving CAR-T cell therapy; AND

VII. Subcutaneous tocilizumab (Actemra®) is considered medically necessary for the FDA approved indication in adults (18 years and older) with Giant Cell Arteritis (GCA) when ONE of the following criteria are met:

Member has tried and had an inadequate response to systemic corticosteroids (e.g., prednisone, methylprednisolone) used in the treatment of GCA for at least 7-10 days; OR
Member has an intolerance, FDA labeled contraindication, or hypersensitivity to ALL systemic corticosteroids; OR
Member’s medication history indicates use of another biologic immunomodulator agent that is FDA labeled or supported by compendia for the treatment of GCA

VIII. When intravenous and subcutaneous tocilizumab (Actemra®) is considered medically necessary, initial therapy will be covered at the doses below based on FDA approved recommendations for a period of 12 months:

Rheumatoid arthritis
- IV (adults): when used in combination with DMARDs or as monotherapy the recommended intravenous starting dose is 4mg per kg every 4 weeks followed by an increase to 8 mg per kg every 4 weeks based on clinical response. The maximum FDA recommended dose for RA is 800 mg per infusion
- SQ (adults): when used in combination with DMARDs or as monotherapy, the recommended subcutaneous starting dose for patients less than 100 kg weight is 162 mg subcutaneously every other week, followed by an increase to every week based on clinical response. For patients at or above 100 kg weight, the recommended starting dose is 162 mg subcutaneously every week. When transitioning from intravenous tocilizumab therapy to subcutaneous tocilizumab therapy, administer the first subcutaneous dose instead of the next scheduled intravenous dose
Giant Cell Artheritis (SQ - adults): 162 mg given once every week (may administer every other week) as a subcutaneous injection in combination with a tapering course of glucocorticoids.
Polyarticular Juvenile Idiopathic Arthritis (PJIA)
- IV (children and adolescents 2 to 17 years):10 mg/kg for patients <30 kg OR 8 mg/kg for patients ≥ 30 kg given once every 4 weeks as 60 minute infusion
- SQ (children and adolescents 2 to 17 years): 162 mg/dose every 3 weeks for patients <30 kg OR 162 mg/dose every 2 weeks for patients ≥ 30 kg
Systemic Juvenile Idiopathic Arthritis (SJIA)
- IV (children and adolescents 2 to 17 years):12 mg/kg for patients <30 kg OR 8 mg/kg for patients ≥ 30 kg given once every 2 weeks as 60 minute infusion
- SQ (children and adolescents 2 to 17 years): 162 mg/dose every 2 weeks for patients <30 kg OR 162 mg/dose every weeks for patients ≥ 30 kg
Cytokine Release Syndrome (CRS) (IV - ages 2 and older): 12 mg/kg for patients <30 kg OR 8 mg/kg for patients ≥ 30 kg, given every 8 hours, if needed, up to a maximum of 4 total doses. The maximum FDA approved recommended dose for CRS is 800 mg per infusion.

[

INFORMATIONAL NOTE

: The FDA approved package inserts recommends that tocilizumab not be initiated in patients with absolute neutrophil counts (ANC) below 2000/mm

, platelet counts below 100,000/mm

, or who have ALT or AST levels above 1.5 times the upper limit of normal (ULN).

As per the FDA approved package insert , interruption of dose or reduction in frequency of administration of intravenous or subcutaneous dose from every week to every other week dosing is recommended for the management of certain dose-related laboratory changes including elevated liver enzymes, neutropenia, and thrombocytopenia.

As per the FDA approved package insert, prior to initiating therapy, patients should be evaluated for Hepatitis B virus (HBV) risk, and if appropriate, HBV infection should be ruled out or treatment initiated.

As per the FDA approved package insert, Actemra can be used alone following discontinuation of glucocorticoids and it can also be used every other week based on clinical considerations

Tocilizumab has not been studied in combination with biological DMARDs and this drug use should be avoided in combination with biological DMARDs due to possibility of increased immunosuppression and increased risk of infection.

The FDA approved package insert recommends reduction of dose from 8 mg/kg is recommended for the management of certain dose-related laboratory changes, including elevated liver enzymes, neutropenia, and thrombocytopenia.

]

IX. Continued therapy will be renewed annually if:

Member continues to meet initial review criteria; AND
If a subcutaneous form of the drug is requested, the requested drug will be administered in an office/outpatient setting by a healthcare professional or home infusion by a home-health nurse and is there is documentation that member will not be self-administering. Documentation must be provided stating the member is unable to self-administer due to one of the following reasons:
Member has shown clinical improvement in signs and symptoms compared to baseline with the requested agent (i.e. slowing of disease progression or decrease in symptom severity and/or frequency); AND
Absence of unacceptable toxicity from the drug (e.g: serious infections, GI perforation, elevated transaminase values, neutropenia, thrombocytopenia, lipid abnormalities, immunosuppression, hypersensitivity reactions including anaphylaxis, hepatic disease/impairment, demyelinating disorders); AND
Member will NOT be using the requested agent in combination with another biologic immunomodulator agent
CRS may NOT be renewed

X. The combined use of Tocilizumab (Actemra) and a TNF or IL-1 inhibitor such as infliximab, etanercept or anakinra, increases the risk of adverse events and has no additional benefit in efficacy; therefore, combination use is not medically necessary.

XI. Tocilizumab (Actemra) intravenous is considered medically necessary for the following off-label indications that have in effect a rating of ‘Category 1’ or ‘Category 2A’ in the current recommendations in the National Comprehensive Cancer Network (NCCN) compendium. Refer to National Comprehensive Cancer Network: Drugs and Biologics Compendium - Tocilizumab (Actemra). Available at: https://www.nccn.org/professionals/drug_compendium/content/

XII. Other uses of intravenous and subcutaneous tocilizumab (Actemra®), including but not limited to, moderate to severe rheumatoid arthritis with no previous treatment failure, Crohn’s disease, systemic lupus erythematosus, ankylosing spondylitis, schizophrenia, Behcet’s syndrome, primary Sjogren’s syndrome, and steroid-refractory gastrointestinal acute graft versus host disease, are considered investigational.

Medicare Coverage

Medicare Advantage Products will follow the Horizon BCBSNJ Medical Policy.

**Note: Bullet 1 of the policy section referring to Site of Administration for Infusion and Injectable Prescription Medications (Policy #142) does not apply for Medicare Advantage Products.

Per Local Coverage Article A53127 Self-Administered Drug Exclusion List, Medicare covers drugs that are furnished “incident to” a physician’s service provided that the drugs are medically reasonable and necessary, approved by the Food and Drug Administration (FDA) and are not usually administered by the patients who take them. Therefore, Medicare Advantage Products will cover Tocilizumab (Actemra) when administered by a licensed medical provider as part of a physician service when the Horizon BCBSNJ Medical policy criteria is met.

Local Coverage Article:Self-Administered Drug Exclusion List: (A53127). Available to be accessed at Novitas Solutions, Inc., Medical Policy Search page: https://www.novitas-solutions.com/webcenter/portal/MedicareJL/pagebyid?contentId=00024370.

Medicaid Coverage

For Horizon NJ Health members, please follow this link for the corresponding HNJH drug policy https://services3.horizon-bcbsnj.com/ddn/NJhealthWeb.nsf

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Horizon BCBSNJ Medical Policy Development Process:

This Horizon BCBSNJ Medical Policy (the “Medical Policy”) has been developed by Horizon BCBSNJ’s Medical Policy Committee (the “Committee”) consistent with generally accepted standards of medical practice, and reflects Horizon BCBSNJ’s view of the subject health care services, supplies or procedures, and in what circumstances they are deemed to be medically necessary or experimental/ investigational in nature. This Medical Policy also considers whether and to what degree the subject health care services, supplies or procedures are clinically appropriate, in terms of type, frequency, extent, site and duration and if they are considered effective for the illnesses, injuries or diseases discussed. Where relevant, this Medical Policy considers whether the subject health care services, supplies or procedures are being requested primarily for the convenience of the covered person or the health care provider. It may also consider whether the services, supplies or procedures are more costly than an alternative service or sequence of services, supplies or procedures that are at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of the relevant illness, injury or disease. In reaching its conclusion regarding what it considers to be the generally accepted standards of medical practice, the Committee reviews and considers the following: all credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, physician and health care provider specialty society recommendations, the views of physicians and health care providers practicing in relevant clinical areas (including, but not limited to, the prevailing opinion within the appropriate specialty) and any other relevant factor as determined by applicable State and Federal laws and regulations.

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Index:
Tocilizumab (Actemra)
Actemra (Tocilizumab)

References:
1. Actemra® (tocilizumab) Prescribing Information. South San Francisco, CA. Genentech, Inc. June 2019.

2. American College of Rheumatology. American College of Rheumatology Subcommittee on Rheumatoid Arthritis Guidelines. Guidelines for the management of rheumatoid arthritis 2008 update. Arthritis & Rheum. 2008 Jun; 59(6):762-84

3. Saag KG, Teng GG, Patkar NM, et al. American College of Rheumatology. 2008 Recommendations for the Use of Nonbiologic and Biologic Disease-Modifying Antirheumatic Drugs in Rheumatoid Arthritis. Arthritis & Rheumatism 2008 June;59(6):762-784.

4. Nishimoto N, Miyasaka N, Yamamoto K, et al. Long-term safety and efficacy of tocilizumab, an anti-IL-6 receptor monoclonal antibody, in monotherapy, in patients with rheumatoid arthritis (the STREAM study): evidence of safety and efficacy in a 5-year extension study. Ann Rheum Dis. 2009;68(10):1580-4.

5. 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):12-9.

6. Genovese MC, McKay JD, Nasonov EL, et al. Interleukin-6 receptor inhibition with tocilizumab reduces disease activity in rheumatoid arthritis with inadequate response to disease-modifying antirheumatic drugs: the tocilizumab in combination with traditional disease-modifying antirheumatic drug therapy study. Arthritis Rheum. 2008;58(10):2968-80.

7. Emery P, Keystone E, Tony HP, et al. IL-6 receptor inhibition with tocilizumab improves treatment outcomes in patients with rheumatoid arthritis refractory to anti-tumour necrosis factor biologicals: results from a 24-week multicentre randomised placebo-controlled trial. Ann Rheum Dis. 2008 Nov;67(11):1516-23.

8. Smolen JS, Beaulieu A, Rubbert-Roth A, et al. Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial. Lancet. 2008;371(9617):987-97.

9. Nishimoto N, Hashimoto J, Miyasaka N, et al. Study of active controlled monotherapy used for rheumatoid arthritis, an IL-6 inhibitor (SAMURAI): evidence of clinical and radiographic benefit from an x ray reader-blinded randomised controlled trial of tocilizumab. Ann Rheum Dis. 2007;66(9):1162-7.

10. Maini RN, Taylor PC, Szechinski J, et al. Double-blind randomized controlled clinical trial of the interleukin-6 receptor antagonist, tocilizumab, in European patients with rheumatoid arthritis who had an incomplete response to methotrexate. Arthritis Rheum. 2006;54(9):2817-29.

11. Yokota S, Imagawa T, Mori M, et al. Efficacy and safety of tocilizumab in patients with systemic-onset juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled, withdrawal phase III trial. Lancet. 2008;371(9617):998-1006.

12. Woo P, Wilkinson N, Prieur AM, et al. Open label phase II trial of single, ascending doses of MRA in Caucasian children with severe systemic juvenile idiopathic arthritis: proof of principle of the efficacy of IL-6 receptor blockade in this type of arthritis and demonstration of prolonged clinical improvement. Arthritis Res Ther. 2005;7(6):R1281-8.

13. U.S. Food and Drug Administration. Center for Drug Evaluation and Research. Actemra NDA sBLA 125276/7, sBLA 125276/10, sBLA 125276/11 approval letter, January 4, 2011. Retrieved January 10, 2011, from http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2011/125276s007,s010,s011ltr.pdf

14. Jones G, Sebba A, Gu J, et al: Comparison of tocilizumab monotherapy versus methotrexate monotherapy in patients with moderate to severe rheumatoid arthritis: the AMBITION study. Ann Rheum Dis 2010; 69(1):88-96.

15. Kremer J, Blanco R, Brzosko M, et al. Tocilizumab inhibits structural joint damage in rheumatoid arthritis patients with inadequate response to methotrexate at 1 year: The LITHE study. Arthritis Rheum. 2010: Nov 19 [Epub ahead of print]

16. Singh JA, Furst DE, Bharat A, et al. 2012 Update of the 2008 American College of Rheumatology Recommendations for the Use of Disease-Modifying Antirheumatic Drugs and Biologic Agents in the Treatment of Rheumatoid Arthritis. Arthritis Care Res (Hoboken). 2012 May;64(5):625-39.

17. Anderson J, Caplan L, Yazdany J, et al. Rheumatoid Arthritis Disease Activity Measures: American College of Rheumatology Recommendations for Use in Clinical Practice. Arthritis Care Res, 2012 May;64(5):640-47.

18. Singh JA, Furst DE, Bharat A, Curtis JR, Kavanaugh et al. 2012 update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken). 2012 May;64(5):625-39

19. Anderson J, Caplan L, Yazdany et al. Rheumatoid arthritis disease activity measures: American College of Rheumatology recommendations for use in clinical practice. Arthritis Care Res (Hoboken). 2012 May;64(5):640-7

20. Kremer JM, Blanco R, Brzosko M,Tocilizumab inhibits structural joint damage in rheumatoid arthritis patients with inadequate responses to methotrexate: results from the double-blind treatment phase of a randomized placebo-controlled trial of tocilizumab safety and prevention of structural joint damage at one year. Arthritis Rheum. 2011 Mar;63(3):609-21.

21. Garnero P, Thompson E, Woodworth T, Rapid and sustained improvement in bone and cartilage turnover markers with the anti-interleukin-6 receptor inhibitor tocilizumab plus methotrexate in rheumatoid arthritis patients with an inadequate response to methotrexate: results from a substudy of the multicenter double-blind, placebo-controlled trial of tocilizumab in inadequate responders to methotrexate alone. Arthritis Rheum. 2010 Jan;62(1):33-43

22. Genovese MC, McKay JD, Nasonov EL, Interleukin-6 receptor inhibition with tocilizumab reduces disease activity in rheumatoid arthritis with inadequate response to disease-modifying antirheumatic drugs: the tocilizumab in combination with traditional disease-modifying antirheumatic drug therapy study. Arthritis Rheum. 2008 Oct;58(10):2968-80.

23. Kolb M, Bhatia M, Gay-Gaddi M, et al. Effective use of tocilizumab for the treatment of steroid-refractory gastrointestinal acute graft versus host disease in a child with very high levels of serum interleukin-6. Ped Blood Canc. 2015;62(2):362-363.

24. National Comprehensive Cancer Network (NCCN): Drugs and Biologics Compendium. Tocilizumab. Available at: http://www.nccn.org/professionals/drug_compendium/MatrixGenerator/Matrix.aspx?AID=42. [Accessed on March 30, 2020].

25. American College of Rheumatology. 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Available at https://www.rheumatology.org/Portals/0/Files/ACR%202015%20RA%20Guideline.pdf. Accessed March 30 2019.

26. Ringold S, Weiss P, Beukelman T, et al. 2013 update of the 2011 American College of Rheumatology Recommendations for the Treatment of Juvenile Idiopathic Arthritis. Arthritis and Rheumatism. Vol 65 October 2013, pp 2499 – 2515.

27. Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988;31:315---24.

28. Singh JA, Guyatt G, Ogdie A, et al. 2018 American College of Rheumatology/National Psoriasis Foundation Guideline for the Treatment of Psoriatic Arthritis. Arthritis & Rheumatology, vol. 71, no. 1, 2018, pp. 5–32., doi:10.1002/art.40726.

29. Ringold S, Angeles-Han ST, Beukelman T, et al. 2019 American College of Rheumatology/Arthritis Foundation Guideline for the Treatment of Juvenile Idiopathic Arthritis: Therapeutic Approaches for Non‐Systemic Polyarthritis, Sacroiliitis, and Enthesitis. Arthritis Care & Research, vol. 71, no. 6, 2019, pp. 717–734., doi:10.1002/acr.23870.

Codes:
(The list of codes is not intended to be all-inclusive and is included below for informational purposes only. Inclusion or exclusion of a procedure, diagnosis, drug or device code(s) does not constitute or imply authorization, certification, approval, offer of coverage or guarantee of payment.)

CPT*

HCPCS

J3262
* CPT only copyright 2020 American Medical Association. All rights reserved. CPT is a registered trademark of the American Medical Association.

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Medical policies can be highly technical and are designed for use by the Horizon BCBSNJ professional staff in making coverage determinations. Members referring to this policy should discuss it with their treating physician, and should refer to their specific benefit plan for the terms, conditions, limitations and exclusions of their coverage.

The Horizon BCBSNJ Medical Policy Manual is proprietary. It is to be used only as authorized by Horizon BCBSNJ and its affiliates. The contents of this Medical Policy are not to be copied, reproduced or circulated to other parties without the express written consent of Horizon BCBSNJ. The contents of this Medical Policy may be updated or changed without notice, unless otherwise required by law and/or regulation. However, benefit determinations are made in the context of medical policies existing at the time of the decision and are not subject to later revision as the result of a change in medical policy
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