BOTOX Injection (Onabotulinumtoxin A) for Chronic Migraine Headaches

BOTOX Injection (Onabotulinumtoxin A) for Chronic Migraine Headaches [For the list of services and procedures that need preauthorization, please refer to www.mcs.com.pr go to Comunicados a Proveedores, and click Cartas Circulares.] Medical Policy: MP-RX-01-11 Original Effective Date: March 24, 2011 Revised: April 14, 2015 Next Revision: March 2016 Related Policies: MP-RX-04-10 Botulinum Toxins (Type A and Type B) (Botox, Dysport, Myobloc, Xeomin ) This policy applies to products subscribed by the following corporations, MCS Life Insurance Company (Commercial), and MCS Advantage, Inc. (Classicare) and, provider s contract, unless specific contract limitations, exclusions or exceptions apply. Please refer to the member s benefit certification language for benefit availability. Managed care guidelines related to referral authorization, and precertification of inpatient hospitalization, home health, home infusion, and hospice services apply subject to the aforementioned exceptions. DESCRIPTION The U.S. Food and Drug Administration (FDA) approved Botox injection (Onabotulinumtoxin A) to prevent headaches in adult patients with chronic migraine in October 2010. Migraine is a highly prevalent disorder characterized by attacks of moderate to severe throbbing headaches that are often unilateral in location, worsened by physical activity, and associated with nausea and/or vomiting, photophobia and phonophobia. (American Headache Society 2015). To diagnose migraine, it is necessary to exclude secondary headache causes and then determine whether the patient has any other coexisting primary headache (e.g., tension type headache). (American Academy of Neurology 2000). Chronic Migraine is a Headache occurring on 15 or more days per month for more than 3 months, which has the features of migraine headache on at least 8 days per month. (International Headache Society 2013). When is used in the treatment of chronic migraines; Botox is given approximately every 12 weeks as multiple injections around the head and neck to try to dull future headache symptoms. Botox has not been shown to work for the treatment of migraine headaches that occur 14 days or less per month, or for other forms of headaches. The most common adverse reactions reported by patients being treated for chronic migraine were neck pain and headache. Onabotulinumtoxin A, marketed as Botox has a Boxed Warning that states the effects of the botulinum toxin may spread from the area of injection to other areas of the body, causing symptoms similar to those of botulism. Those symptoms include swallowing and breathing difficulties that can be life-threatening. 1

COVERAGE Benefits may vary between groups and contracts. Please refer to the appropriate member certificate and subscriber agreement contract for applicable diagnostic imaging, DME, laboratory, machine tests, benefits, and coverage. INDICATIONS I. For the Evaluation of medical necessity of Botox in members of Classicare Line of Business (LOB) with Chronic Migraines, please refer to the following LCD: Local Coverage Determination (LCD) for Botulinum Toxins (L29103). II. For members of Commercial Line of Business (LOB);, (MCS) will consider medically necessary the administration of BOTOX Injection (Onabotulinumtoxin A), for prophylactic (preventive) treatment of headaches in adults with Chronic Migraines when All of the following criterion are met: 1. The member must have a diagnosis of chronic migraines (history of migraine suffering from headaches on 15 or more days per month with headaches lasting four (4) hours a day or longer). 2. Member must be in a treatment for migraines headaches by a neurologist. 3. There must be a documentation stating that the traditional methods of treatment have been tried and proven unsuccessful. The documentation must demonstrate the following: Documentation of failed trials of at least three (3) therapeutic groups of preventive medications, where at least one of them is a first line agent, such as Propanodol, Amitriptyline, Topiramate or Valproic acid and its derivate. There must be documentation showing that these medications were titrated to the maximum tolerated doses. Should a Member have a contraindication to a specific treatment or medication group, this is considered as a treatment failure, and must be documented within the progress notes. The trial period of each therapeutic group should have been at least three (3) months with the appropriate therapeutic doses. 2

4. Botox Injection should be recommended, monitored and administered by the treating neurologist. 5. For continuation of Botulism toxin therapy the Member must demonstrate a significant decrease in the number and frequency of headaches and an improvement in function upon receiving Botulinum Toxin. LIMITATIONS 1. MCS will only cover One (1) Injection per site regardless of the number of injections made into the site. (A site is defined as including muscles of a single contiguous body part, such as, a single limb, eyelid, face, neck, etc.). 2. MCS WILL NOT covers additional injections of botulinum toxin if treatment failure occurs after two (2) consecutive injections, using maximum dose for the size of the muscle. 3. Treatment of wrinkles using Botulinum toxins is considered to be cosmetic, and NOT covered. 4. To provide coverage for treatment the medical record must support the specific symptoms and parameters mentioned under indications. 5. Safety and effectiveness have not been established for the prophylaxis of episodic migraine (14 headache days or fewer per month). 6. The recommended re-treatment schedule is every 12 weeks. 7. MCS WILL NOT considers the following medical criteria for Botox Therapy due to insufficient literature to support clinical effectiveness: As a first line management for migraine headaches. CONTRAINDICATIONS 1. Inflammation or infection at the site of injection is presented. - Administration of Onabotulinumtoxin A BOTOX is contraindicated in the presence of infection at the proposed injection site(s). 2. Allergy to drug was observed - Onabotulinumtoxin A BOTOX is contraindicated in patients who are hypersensitive to any botulinum toxin preparation or to any of the components in the formulation (e.g., Albumin). 3

3. When is administered with some drugs like aminoglycosides antibiotics or other drugs that alter neuromuscular transmission. 4. When administered with Muscle Relaxants in muscles with excessive weakness or muscle atrophy. WARNINGS AND PRECAUTIONS 1. Black Box Warning: Spread of Toxin Effect- A boxed warning in the labeling of OnabotulinumtoxinA products includes post-marketing reports of the distant spread of botulinum toxic effects that have resulted in symptoms suggestive of systemic botulism (including respiratory compromise and death) after the use of botulinum toxins types A and B. These effects have been seen in patients who received the medication for a variety of conditions and a wide range of doses. 2. Lack of Interchangeability between Botulinum Toxin Products. - The potency Units of BOTOX are specific to the preparation and assay method utilized. They are not interchangeable with other preparations of botulinum toxin products and, therefore, units of biological activity of BOTOX cannot be compared to nor converted into units of any other botulinum toxin products. 3. Onabotulinumtoxin A should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. 4. Caution should be exercised when Onabotulinumtoxin A is administered to a nursing woman. 5. Safety and effectiveness in patients below the age of 18 years have not been established when BOTOX is administered. CODING INFORMATION CPT Codes (List may not be all inclusive) CPT Codes DESCRIPTION 64615 Chemodenervation of muscle(s); innervated by facial, trigeminal, cervical spinal and accessory nerves, bilateral (e.g., for chronic migraine) Current Procedural Terminology (CPT ) 2015 American Medical Association: Chicago, IL. 4

ICD-9 CM Diagnosis Codes (List may not be all inclusive) ICD-9 CM CODES DESCRIPTION 346.71 Chronic migraine without aura, with intractable migraine, so stated, without mention of status migrainosus 346.73 Chronic migraine without aura, with intractable migraine, so stated, with status migrainosus 2015 ICD-9-CM For Physicians, VOLUMES I & II, Professional Edition (American Medical Association). HCPCS CODES (List may not be all inclusive) HCPCS CODES J0585 Injection, onabotulinumtoxinaa, 1 unit 2015 HCPCS LEVEL II Professional Edition (American Medical Association). DESCRIPTION ICD-10 Codes (Preview Draft) In preparation for changes in the coding systems form ICD- 9 to ICD -10, this policy includes a sample list of ICD-10 codes for your reference. These codes may become subject to changes or modifications since they will be in effect on October 1, 2015. ICD 10 CODES DESCRIPTION G43.719 Chronic migraine without aura, intractable, without status migrainosus G43.711 Chronic migraine without aura, intractable, with status migrainosus REFERENCES 1. AHFS. Drug Information. Botullinum Toxin. AHFS Class: Other Miscellaneous Therapeutic Agents (92:92). Monograph Electronic Version. Dated: 2015. Accessed April 01, 2015. Available at URL Address: http://www.ahfsdruginformation.com/support/login.aspx 2. Alberto Proietti Cecchini & Licia Grazzi. Emerging Therapies for Chronic Migraine. 2014. Curr Pain Headache Rep (2014) 18:408. Accessed March 25, 2015. Available at URL Address: http://link.springer.com/article/10.1007/s11916-014-0408-5# 3. Alex Rodrigo Espinoza Giacomozzi, et al. Latin American Consensus on Guidelines for Chronic Migraine Treatment. Arq Neuropsiquiatr 2013; 71 (7): 478-486. Accessed March 25, 2015. Available at URL Address: http://www.scielo.br/pdf/anp/v71n7/0004-282x-anp-71-07-478.pdf 5

4. Allergan Pharmaceuticals Package Insert. Botox (Botulinum Toxin Type A) purified Neurotoxin Complex. Revised: 2/2014. Accessed March 16, 2015. Available at URL address: http://www.allergan.com/assets/pdf/botox_pi.pdf 5. Allergan, Inc. Botox Fact Sheet. 2010, Irvine, CA 92612. Accessed March 16, 2015. Available at URL address: http://www.google.com.pr/url?url=http://www.ghsplasticsurgery.com/mydocuments/botox_fa ct_sheet.pdf&rct=j&frm=1&q=&esrc=s&sa=u&ei=viahvcexoyzisasxmigoaq&ved=0cbmqfjaa &usg=afqjcngnzwxnzpkthf9c1gzl9204c8ecqg 6. American Academy of Family Physicians (AAPP). Medications for Migraine Prophylaxis. Amen Fam Physician 2006; 73: 72-8, 79-80. Accessed March 25, 2015. Available at URL Address: http://www.aafp.org/afp/2006/0101/p72.html 7. American Academy of Neurology (AAN). Assessment: Botulinum neurotoxin in the treatment of autonomic disorder and pain (an evidence based review): Report of the therapeutic and technology assessment subcommittee of the American Academy of Neurology. M. Naumann, Y. So, C.E. Argoff, et al., Neurology 2008; 70; 1707. Approved by the AAN Board of Directors on January 30, 2008. Information is still current. Accessed March 16, 2015. Available at URL address: http://www.neurology.org/content/70/19/1707.full.html 8. American Academy of Neurology (AAN). Practice parameter: Evidence-based guidelines for migraine headache (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Stephen D. Silberstein, MD, FACP, for the US Headache Consortium. Published in Neurology 2000; 55:754-763. Approved by the AAN Board of Directors June 9, 2000. This information is still current. Accessed Mach 16, 2015. Available at URL address: http://www.neurology.org/content/55/6/754.long 9. American Headache Society. American Headache Society Evidence Assessment-The Acute Treatment of Migraine in Adults: The American Headache Society Evidence Assessment of Migraine Pharmacotherapies. (2015) Headache; 55:3-20. Accessed June 12, 2015. Available at URL Address: http://www.headachejournal.org/springboardwebapp/userfiles/headache/file/head%20acute %20Guidelines.pdf 10. Aurora S. Botulinum Toxin Type A for the treatment of migraine. Expert opinion Pharmacotherapy. 2006; 7 (8) 1085-1095. Accessed March 16, 2015. Available at URL address: http://www.ingentaconnect.com/content/apl/eop/2006/00000007/00000008/art00010 - Document require membership to get full access. 11. Centers for Medicare and Medicaid Services (CMS) / First Coast Service Options, Inc. Local Coverage Determination (LCD) for Botulinum Toxins (L29103). Original Determination Effective Date: 03/02/2009. Revision Effective Date: 02/13/2014. Updated: 07/01/2014. Accessed March 16, 2015. Available at URL address: http://www.cms.gov/medicare-coveragedatabase/details/lcddetails.aspx?lcdid=29103&contrid=371&ver=23&contrver=1&cntrctrselected=198*1&cntrctr= 6

198&name=First+Coast+Service+Options%2c+Inc.+(09202%2c+MAC+- +Part+B)&s=46&DocType=Active&bc=AggAAAIAKAAAAA%3d%3d& 12. California Technology Assessment Forum (CTAF). An Action Guide for the Treatment of Migraine: Payers and Policymakers. Completed by: Institute for Clinical and Economic Review. Dated: September 2014. Accessed March 23, 2015. Available at URL Address: http://ctaf.org/sites/default/files/u148/ctaf_migraine_action_guide_payers_final.pdf 13. David W. Dodick, MD. Et al. OnabotulinumtoxinA for Treatment of Chronic Migraine: Pooled Results From the Double-Blind, Randomized, Placebo-Controlled Phases of the PREEMPT Clinical Program. 2010. Cephalalgia July 2010 vol. 30 no. 7 804-814. Accessed March 25, 2015. Available at URL Address: http://cep.sagepub.com/content/30/7/804 14. Divakara Kedlaya. EMedicine: Botulinum Toxin, Overview. Updated: February 07, 2014. Accessed March 16, 2015. Available at URL address: http://emedicine.medscape.com/article/325451-overview 15. ECRI Institute. Botulinum Toxin for Prevention and Treatment of Migraine. Published: 02/27/2008. Updated 05/28/2008. Searched March 16, 2015. This document has been archived by ECRI Institute and is no longer available. Available at URL address: https://www.ecri.org/pages/searchresults.aspx?k=botulinum%20toxin%20for%20prevention% 20and%20Treatment%20of%20Migraine&mo=true 16. ECRI Institute. Health Technology Forecast News Brief: Study suggests botulinum toxin provides minimal relief from chronic migraine headaches. Published: 05/04/2012. Accessed March 16, 2015. Available at URL address: https://www.ecri.org/components/forecast/pages/13079.aspx 17. Evers S. Vollmer-Haase J, Schwaag S, et al. Botulinum toxin A in the prophylactic treatment of migraine- a randomized, double-blind, and placebo controlled study. Cephalagia. 2004; 24(10) 838-843. Accessed March 16, 2015. Available at URL address: http://www.ncbi.nlm.nih.gov/pubmed/15377314 18. Giacomozzi, Alex Rodrigo Espinoza et al. Latin American consensus on guidelines for chronic migraine treatment. 2013. Arq. Neuro-Psiquiatr. Vol.71, n.7, pp. 478-486. Accessed March 23, 2015. Available at URL Address: http://www.scielo.br/pdf/anp/v71n7/0004-282x-anp-71-07- 478.pdf 19. Gold Standard / Elsevier. Clinical Pharmacology. Onabotulinumtoxin A: Indications & Contraindications. Last Revision Date: 12/16/2014. Accessed March 16, 2015. Available at URL address: https://www.clinicalpharmacology.com/forms/drugoptions.aspx?cpnum=1219&n=botox&t=0 20. International Headache Society. Headache Classification Committee of the International Headache Society (HIS). The International Classification of Headache Disorders, 3rd edition (beta version). 2013 Cephalalgia: 33 (9) pp: 629-808. Accessed March 24, 2015. Available at URL 7

Address: http://www.ihs-classification.org/_downloads/mixed/international-headache- Classification-III-ICHD-III-2013-Beta.pdf 21. Modar Khalil, Hassan W. Zafar, Vistoria Quarshie and Fayyaz Ahmed. Prospective Analysis of the Use of Onabotulinumtoxin A (BOTOX) in the Treatment of Chronic Migraine; real-life data in 254 patients from Hull, UK. The Journal of Headache and Pain. 2014, 15: 54. Accessed March 23, 2015. Available at URL Address: http://www.thejournalofheadacheandpain.com/content/pdf/1129-2377-15-54.pdf 22. National Institute for Health and Care Excellence. NICE technology appraisal guidance [TA260]. Botulinum toxin type A for the prevention of headaches in adults with chronic migraine. Dated: June 2012. Accessed April 01, 2015. Available at URL Address: http://www.nice.org.uk/guidance/ta260/chapter/4-consideration-of-the-evidence 23. National Institute of Health / National Institute of Neurological Disorders and Stroke. Headache: Hope through Research. October 2009. Last updated February 23, 2015. Accessed March 16, 2015. Available at URL address: http://www.ninds.nih.gov/disorders/headache/detail_headache.htm#156653138 24. National Guideline Clearing House. Institute for Clinical Systems Improvement (ICSI). Diagnosis and treatment of headache. Bloomington (MN): Institute for Clinical Systems Improvement (ICSI); 2011 Jan. 84 p. This is the current release of the guideline. Accessed March 16, 2015. Available at URL address: http://www.guideline.gov/content.aspx?id=43791 25. Ninan T. Mathew, MD; Sayyed Farhan A. Jaffri, MD., A Double-Blind Comparison of Onabotulinumtoxin A (BOTOX ) and Topiramate (TOPAMAX ) for the Prophylactic Treatment of Chronic Migraine: A Pilot Study. 2009. Headache; 49(10):1466-1478. Accessed March 25, 2015. Available at URL Address: http://www.medscape.com/viewarticle/715729 26. Thomson Micromedex DrugDex. Onabotulinumtoxin A - Indications & Contraindications. Retrieved March 20, 2015 from https://www.thomsonhc.com/micromedex2 27. UptoDate. Chronic Migraine. Ivan Garza, MD., Todd J. Schwedt, MD, MSCI. Literature review current through: Feb 2015. This Topic last Updated: January 28, 2015. Accessed March 19, 2015. Available at URL Address: http://www.uptodate.com/contents/chronicmigraine?source=search_result&search=chronic+migraine&selectedtitle=1%7e150 28. UptoDate. Pathophysiology, clinical manifestations, and diagnosis of migraine in adults. F Michael Cutrer, MD., Zahid H. Bajwa, MD., Ashraf Sabahat, MD. Literature review current through: Feb 2015. This Topic last Updated: April 21, 2014. Accessed March 23, 2015. Available at URL Address: http://www.uptodate.com/contents/pathophysiology-clinical-manifestationsand-diagnosis-of-migraine-inadults?source=machinelearning&search=when+a+pain+reliever+does+not+control+migraine&s electedtitle=3%7e150&sectionrank=5&anchor=h13436872#h13436872 8

29. UptoDate. Preventive treatment of migraine in adults: Prophylactic treatment of migraine and tension type headache. Bajwa, Zhid, M.D., Sabahat, Ashraf, M.D. Literature review current through: Feb 2015. This topic last updated: Jan 28, 2015. Accessed March 16, 2015. Available at URL address: http://www.uptodate.com/contents/preventive-treatment-of-migraine-inadults#h14 30. U.S. Food and Drug Administration. FDA approves Botox to treat chronic migraine. For Immediate Release: October 15, 2010. Accessed March 16, 2015. Available at URL address: http://www.fda.gov/newsevents/newsroom/pressannouncements/2010/ucm229782.htm 31. U.S. Food and Drug Administration. Medication Guide for Botox (Onabotulinumtoxin A) for Injection. Revised 09/2013. Accessed March 16, 2015. Available at URL address: http://www.fda.gov/downloads/drugs/drugsafety/ucm176360.pdf POLICY HISTORY DATE ACTION COMMENT March 24, 2011 March 16, 2012 Origination of Policy Yearly Review February 7, 2013 Revised References updated. Added new references, numbers: 10, 12, 15, 17 & 19. To Coding Information: Added new CPT Code 64615 & Notes 1 & 2. May 16, 2013 Reviewed References updated. ALL changes from February 7, 2013 were reviewed by the Medical Card System (MCS) Medical Advisory Committee (MAC) on May 16, 2013. Final changes that were approved are documented under February 7, 2013. February 21, 2014 Revised To the Coding section: A new ICD-10 Codes (Preview Draft) section was added to the policy. March 18, 2014 Revised References updated. April 14, 2015 Revised References updated. To the Coding section: New CPT New code CPT 64616 was added to the Policy. To the References section: Reference # 10 was added to the Policy. To the Title: Word Chronic was added to the Title for make a reference in the Type of Migraine contemplated and described into this Medical Policy. To the Description Section: 1. New information of Migraine was added from: American Academy of Neurology (AAN). Practice parameter: Evidence-based guidelines for migraine headache (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Stephen D. Silberstein, MD, FACP, for the US Headache Consortium. Published in Neurology 2000; 55:754-763. Approved by the AAN Board of Directors June 9, 2000. This information is still current. 2. New Concept of Chronic Migraine was added from: International Headache Society. Headache Classification Committee of the International Headache Society (HIS). The International 9

Classification of Headache Disorders, 3rd edition (beta version). 2013 Cephalalgia: 33 (9) pp: 629-808. To the Indications Section: 1. Indications were separated in two different sections; Section I for Classicare LOB and Section II for Commercial LOB. 2. Phrase with the appropriate therapeutic doses was added to the indication #5 as discussed at requested by the MAC April, 14 2015. To the Limitations Section: 1. Limitation #3 was unified with part of the limitation #8 and then deleted from the medical policy as requested MAC April 14, 2015. 2. Limitation #5 was deleted from the policy as requested by Dra. Wheeler on April, 2015. New WARNINGS AND PRECAUTIONS Section was added to the Policy. To the Coding Information Section: CPTs codes (64612 and 64616) were deleted from the Policy as informed in the MAC April 14, 2015. To the References Section: New References (#1, 2, 3, 6, 9, 12, 13, 18, 20, 21, 22, 25, 27, and 28) were added to the Policy. This document is for informational purposes only. It is not an authorization, certification, explanation of benefits, or contract. Receipt of benefits is subject to satisfaction of all terms and conditions of coverage. Eligibility and benefit coverage are determined in accordance with the terms of the member s plan in effect as of the date services are rendered., (MCS) medical policies are developed with the assistance of medical professionals and are based upon a review of published and unpublished information including, but not limited to, current medical literature, guidelines published by public health and health research agencies, and community medical practices in the treatment and diagnosis of disease. Because medical practice, information, and technology are constantly changing, Medical Card System, Inc., (MCS) reserves the right to review and update its medical policies at its discretion. Medical Card System, Inc (MCS) medical policies are intended to serve as a resource to the plan. They are not intended to limit the plan s ability to interpret plan language as deemed appropriate. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment they choose to provide. 10