I.  FDA-Approved Self-administered Products (excluding Mavenclad)

FDA-Approved Self-administered Products (excluding Mavenclad) may be considered medically necessary when ALL of the following are met: 

         A.  ONE of the following:

1. Information has been provided that the patient has been treated with the requested agent within the past 90 days OR            

2. The prescriber states the patient has been treated with the requested agent within the past 90 days AND is at risk if therapy is changed OR

3. The patient has an FDA labeled indication for the requested agent as listed above (e.g. MRI confirmed Clinically Isolated Syndrome (CIS),    Relapsing Remitting Multiple Sclerosis or Secondary Progressive Multiple Sclerosis) AND

         B.  The prescriber is a neurologist or the prescriber has consulted with a neurologist AND

         C.  The patient is NOT currently being treated with an additional disease modifying agent (DMA) for the requested indication AND

         D.  If the request is for a non-preferred product, then ONE of the following: 

a. The patient has tried and failed at least ONE of the preferred self-administerd agents

OR

b. The patient has FDA approved contraindication to ALL preferred self-administered agents

               E.  The patient does NOT have any FDA labeled contraindications to the requested agent AND

         F.  The requested quantity (dose) does not exceed the FDA labeled maximum dose

Length of Approval:  12 months. NOTE: For agents requiring a starter dose for initial use, except Mayzent, the starter dose will be approved per the dose table below and the maintenance dose will be approved for the remainder of 12 months. Mayzent will be approved only for the maintenance dose for 12 months.

Renewal

FDA-Approved Self-administered Products (excluding Mavenclad) may be considered medically necessary when ALL of the following are met:

           1. The patient has been previously approved for the requested agent through the BCBSNE Prior Authorization process AND

               2. The patient has had clinical benefit with the requested agent

II.  Mavenclad Initial Evaluation

     Mavenclad may be considered medically necessary when ALL of the following are met: 

         A.  ONE of the following:

               1.  Information has been provided that the patient has been treated with the requested agent within the past 90 days OR 

               2.  The prescriber states the patient has been treated with the requested agent within the past 90 days AND the patient is at risk if therapy is changed OR

               3.  The patient has an FDA approved diagnosis for the requested agent AND 

B. ONE of the following:

 1. If the patient is currently being treated with the requested agent, the patient has NOT completed 2 courses of the requested agent (one

              course consists of 2 cycles of 4-5 days each) OR

 2. The patient has been treated with at least 1 preferred generic MS therapy AND

         C. The prescriber is a neurologist or the prescriber has consulted with a neurologist AND                 

         D. The patient is NOT currently being treated with an additional disease modifying agent (DMA) for the requested indication AND

               E. The patient does NOT have any FDA labeled contraindications to the requested agent AND

         F. The requested quantity (dose) does not exceed the FDA labeled maximum dose based on the patient’s weight

       Length of Approval: 36 weeks for new starts OR if patient is currently taking the requested agent, approve for remainder of the annual course (1 course  consists of 2 cycles of 4-5 days)

Mavenclad Renewal Evaluation

Mavenclad will be approved when ALL of the following are met:

        1.  The patient has been previously approved for the requested agent through the BCBSNE Prior Authorization process AND

        2.  The patient has had clinical benefit with the requested agent 

        3.  It has been at least 35 weeks but not more than 67 weeks since the last dose of the requested agent AND

        4.  The patient has NOT completed 2 courses with the requested agent (one course consists of 2 cycles of 4-5 days) AND

        5.  The requested dose does not exceed tyhe maximum FDA labeled dose for the patient's weight and the dose is achieved by using the fewest number of   tablets necessary based on patient's weight (e.g., two 10 tablet packs instead of four 5 tablet packs).

Length of Approval: 3 months

III.  FDA-Approved Healthcare Administered Products (Lemtrada, Ocrevus, Tysabri)

      FDA-Approved Healthcare Administered Products may be considered medically necessary when ALL of the following are met: 

         A.  The request is for Ocrevus for a diagnosis of Primary Progressive Multiple Sclerosis OR

 B.  ONE of the following:   

                1.  Information has been provided that the patient has been treated with the requested agent within the past 90 days OR

                2.  The prescriber states the patient has been treated with the requested agent within the past 90 days AND is at risk if therapy is changed OR

                3.  The patient has an FDA labeled indication for the requested agent as listed above AND

         C.  The prescriber is a neurologist, or the prescriber has consulted with a neurologist AND   

         D.  The patient is NOT currently being treated with an additional disease modifying agent (DMA) for the requested indication AND

         E. The patient does NOT have any FDA labeled contraindications to the requested agent AND

         F.  The requested quantity (dose) does not exceed the FDA labeled maximum dose AND

Length of Approval:  12 months

Renewal

FDA-Approved Healthcare Administered Products may be considered medically necessary when ALL of the following are met:

1. The patient has been previously approved for the requested agent through the BCBSNE Prior Authorization process AND

2.  The patient has had clinical benefit with the requested agent 

Length of Approval:  12 months

Multiple sclerosis

Multiple sclerosis (MS) is a disorder of the central nervous system (CNS) characterized by demyelization, inflammation, and degenerative changes.  Most people with MS experience relapses and remissions of neurological symptoms, particularly early in the disease, and clinical events are usually associated with areas of CNS inflammation. Gradual worsening or progression, with or without subsequent acute attacks of inflammation or radiological activity, may take place early, but usually becomes more prominent over time. While traditionally viewed as a disease solely of CNS white matter, more advanced imaging techniques have demonstrated significant early and ongoing CNS gray matter damage as well.¹¹

Those diagnosed with MS may have many fluctuating and disabling symptoms (including, but not limited to, fatigue, impaired mobility, mood and cognitive changes, pain and other sensory problems, visual disturbances, and elimination dysfunction), resulting in a significant impact on quality of life for patients and their families. Diagnosis of MS is primarily based on clinical presentation. The core requirement for the diagnosis is demonstration of CNS lesion dissemination and presence of symptoms such as visual loss, motor function loss, difficulty with balancing, and vertigo. There are currently four major types of MS: clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS), primary progressive MS (PPMS), and secondary progressive MS (SPMS).²⁰

Clinically isolated syndrome

CIS is a first episode of neurologic symptoms caused by inflammation and demyelination in the central nervous system. The episode, which by definition must last for at least 24 hours, is characteristic of multiple sclerosis but does not yet meet the criteria for a diagnosis of MS because people who experience a CIS may or may not go on to develop MS. When CIS is accompanied by lesions on a brain MRI that are similar to those seen in MS, the person has a high likelihood of a second episode of neurologic symptoms and diagnosis of relapsing-remitting MS. When CIS is not accompanied by MS-like lesions on brain MRI, the person has a much lower likelihood of developing MS.²⁰

Relapsing remitting multiple sclerosis (RRMS)

RRMS is characterized by clearly defined attacks (relapses) of new or increasing neurologic symptoms. These relapses are followed by periods of partial or complete recovery. There is no or minimal disease progression during the periods between disease relapses, though individual relapses may result in severe residual disability. The course of MS varies, however, about 85-90% of individuals with MS demonstrate a relapsing pattern at onset, which transitions over time in the majority of untreated patients to a pattern of progressive worsening with few or no relapses or MRI activity (SPMS).²⁰

Secondary progressive multiple sclerosis (SPMS)

SPMS begins as RRMS, but over time the disease enters a stage of steady deterioration in function, unrelated to acute attacks. Typically, when SPMS stage is reached, the relapse rate is also reduced. Prior to the era of disease-modifying agents (DMAs), approximately half of patients diagnosed with relapsing MS would progress to SPMS by 10 years, and 80-90% would do so by 25 years.²⁰

2017 McDonald Criteria for the diagnosis of Multiple Sclerosis:

Diagnostic criteria for multiple sclerosis combining clinical, imaging, and laboratory evidence have evolved over time. The increasing incorporation of paraclinical assessments, especially imaging, to supplement clinical findings has allowed earlier, more sensitive, and more specific diagnosis.^18,19

The diagnosis of MS requires elimination of more likely diagnoses and demonstration of dissemination of lesions in the CNS in space and time.¹⁸

Misdiagnosis of multiple sclerosis remains an issue in clinical practice, and several factors that potentially increase this risk have been identified. Multiple sclerosis has heterogeneous clinical and imaging manifestations, which differ between patients over time. There is no single pathognomonic clinical feature or diagnostic test; diagnosis of multiple sclerosis relies on the integration of clinical, imaging, and laboratory findings. MRI abnormalities associated with other diseases and non-specific MRI findings, which are common in the general population, can be mistaken for multiple sclerosis. The increasingly strong focus on timely diagnosis to alleviate uncertainty for patients and allow initiation of disease-modifying therapies might also increase the risk of misdiagnosis.¹⁸

With increasing availability and use of MRI, incidental T2 hyperintensities on brain imaging are common, the subset of individuals with MRI findings that are strongly suggestive of multiple sclerosis lesions but with no neurological manifestations or other clear-cut explanation are said to have radiologically isolated syndrome. There is no consensus on whether patients with radiologically isolated syndrome will develop MS. Some practitioners argue that these patients have a high likelihood of developing MS while others argue that up to two-thirds of these patients will not receive a diagnosis of MS in 5 years.  A consensus panel decided to require clinical manifestations to make the diagnosis of MS (2017 McDonald Criteria for the diagnosis of Multiple Sclerosis).¹⁸

Treatment of MS

Both the Multiple Sclerosis Coalition and the American Academy of Neurology recommend initiating treatment with a DMA FDA approved for the patient’s phenotype as soon as possible following the diagnosis of multiple sclerosis. There are several DMAs with at least 10 mechanisms of action available to people with MS. The factors affecting choice of therapy at any point in the disease course are complex and most appropriately analyzed and addressed through a shared decision-making process between the individual and the treating clinician.^11,14

The Multiple Sclerosis Coalition recommends that clinicians should consider prescribing a high efficacy medication such as alemtuzumab, cladribine, fingolimod, natalizumab or ocrelizumab for newly diagnosed individuals with highly active MS. Clinicians should also consider prescribing a high efficacy medication for individuals who have breakthrough activity on another DMA regardless of the number of previously used agents.⁴ The American Academy of Neurology has recommended alemtuzumab, fingolimod, and natalizumab as options for patients with MS with highly active MS. There lacks a consensus for what constitutes as highly active MS, however.⁷ The National Institute for Health and Care Excellence (NICE) defines rapidly evolving severe RRMS as two or more disabling relapses in 1 year, and one or more gadolinium-enhancing lesions on brain MRI or a significant increase in T2 lesion load compared with a previous MRI.¹⁵

Lack of response to DMAs is hard to define, as most patients with MS are not free of all disease activity. Relapses or new MRI detected lesions may develop after initiation of a DMA and before the treatment becomes effective for patients.  When determining efficacy, sufficient time for the DMA therapy to take full effect and patient adherence are important considerations. Evidence of one or more relapses, 2 or more unequivocally new MRI-detected lesions, or increased disability on examination while being treated with a DMA for a 1 year period suggests a sub-optimal response, an alternative regimen (e.g., different mechanism of action) should be considered to optimize therapeutic benefit.¹³ A National MS Society consensus statement recommends changing from one disease modifying therapy to another only for medically appropriate reasons (e.g. lack of efficacy, adverse effects, or if better treatments options become available).¹¹

Existing MS therapies are partly effective in halting ongoing inflammatory tissue damage and clinical progression. MS pathogenesis is complex and probably heterogeneous among patient, suggesting that combination therapy strategies that target a range of disease mechanisms might be more effective than medications used as monotherapy. Although preliminary studies have provided favorable results, however, several subsequent large, randomized, controlled trials have had negative of conflicting results. There also may be more adverse reactions associated with combination therapies due to the additive effect.²¹

1.       If a patient is currently stable on one of the above medications they shall remain on their current therapy. (NEW MEMBERS ONLY)

2.       Dosing:  Doses will meet FDA-approved dosing recommendations.

3.       Authorization is for 36 months.  NOTE:  if on NetResults formulary, authorization is for 12 months.  For agents requiring a starter dose for initial use, the starter dose will be approved per the dose table and the maintenance dose will be approved for the remainder of 12 months.

4.    No therapies listed in this policy shall be used in combination with each other