Pharmacy and Therapeutics Committee Meeting Summary - December 8, 2006

Agenda and Introduction

The Medicaid Pharmacy & Therapeutics Committee met on Friday, December 8, 2006 from 9:00 a.m. to 2:00 p.m. in Meeting Room 6, Concourse, Empire State Plaza, Albany, New York.

Linda Jones, NYS Department of Health, Office of Medicaid Management (DOH/OMM), introduced Dr. David Lehmann, MD, PharmD, as a new Committee member. Dr. Lehmann is a Professor of Medicine and Pharmacology, SUNY Upstate Medical University.

A. Background Materials Provided:

The Committee was provided copies of written materials submitted by interested parties in advance of the meeting.

B. Public Comment Period:

The following speakers provided comment to the committee:

1. Schwartz, Joseph, MD, Dermatologist, Troy, NY
2. Pederson, Gary, Consultant, Jasos Group, LLC/Representing Allergan Inc, Lake Mary, FL
3. D'Arienzo, Peter A., MD, Ophthalmologist, Manhasset Eye Physicians, PC, Manhasset, NY
4. Toth, Christina, PharmD, Manager, Medical Affairs, Daiichi Sankyo/Pharmaceutical, Parsippany, NJ
5. Menger, Peter, MD, Attending Physician, Manhattan Eye and Ear Infirmary and North Shore University Hospital, Glendale, NY
6. Wong, Mary Lee, MD, Assistant Professor of Medicine and Pediatrics at Albert Einstein School of Medicine, Beth Israel Hospital, New York, NY
7. Thomas, Jessy, PharmD, Health Outcomes and Pharmacoeconomics Regional Medical Liaison, Amgen, Princeton, NJ
8. Sardo, Pamela, PharmD, BS, Regional Clinical Executive, Abbott Laboratories, Parker, TX
9. Kramer, Sara B., MD, Rheumatologist, Clinical Assistant Professor of Medicine, NY University School of Medicine, Chair, NY Chapter Government Affairs Committee, Arthritis Foundation, Inc., NY Chapter, New York, NY
10. Shapiro, Lee S., MD, The Center for Rheumatology, Albany, NY
11. Virtanen, Debra, MS, PT, Chair Arthritis Foundation NENY, Owner Riverfront Physical Therapy, Troy, NY
12. Sachdeva, Amisha, PharmD, Cardiovascular Medical Science Liaison-Global Medical Affairs, Schering-Plough, Bridgewater, NJ

C. Key Issues Raised by Interested Parties and Pharmacy and Therapeutics Committee Response:

Public comments:

On the topic of identification of preferred drugs in the therapeutic class of Ophthalmic Quinolones:

• Information regarding clinical trial results (pharmacokinetics, efficacy in the coverage of gram positive and gram negative bacteria, susceptibility of resistant bacteria, ocular penetration, dosing, safety, and tolerability) for drugs in this category was presented.
• The Committee was asked to consider the use of these medications with regard to resistance, cost effectiveness, and the inclusion of preservative in ocular products, in the review of this category.

On the topic of identification of preferred drugs in the therapeutic class of Otic Quinolones:

• Information regarding clinical trial results (indications, dosing, mechanism of action, safety, efficacy, and adverse reactions) for drugs in this category was presented.
• The Committee was asked to consider the use of these medications in otitis externa (OE), acute otitis media with tympanostomy tubes (AOMTT), and chronic suppurative otitis media (CSOM) with perforated tympanic membranes in the review of this category.

On the topic of identification of preferred drugs in the therapeutic class of Ophthalmic Antihistamines:

• Information regarding clinical trial results (safety, efficacy, indications, adverse reactions, antihistaminic and mast cell stabilizing properties) for drugs in this category was presented.
• The Committee was asked to consider the head to head trial data, products with wetting agents, use of these medications in special populations, use in initial versus late breakthrough ocular symptoms, and cost effectiveness in the review of this category.

On the topic of identification of preferred drugs in the therapeutic class of Immunomodulators (Injectable):

• Information regarding clinical trial results (mechanism of action, safety, efficacy, indications, adverse reactions, onset of action, use with or without other disease modifying antirheumatic drugs [DMARDs]) for drugs in this category was presented.
• The Committee was asked to consider the importance of controlling rheumatoid arthritis, the effect of these drugs on quality of life, ease of administration of the drugs, the use of these drugs versus DMARDs, post marketing data, and the improvements in measures of disease activity in the review of this category.

On the topic of the Review of the Cholesterol Absorption Inhibitors (CAIs) therapeutic class:

• Information regarding ezetimibe (Zetia) clinical trial results (mechanism of action, efficacy, including use as a primary or secondary lipid-lowering agent, indications, pharmacokinetics, dosing, and safety) was presented.
• The Committee was asked to consider ezetimibe (Zetia) as a safe, effective first or second line lipid-lowering alternative.

Pharmacy and Therapeutics Committee Response:

• A committee member asked that the presenters speaking on behalf of ophthalmic quinolones address their product's advantage, if any, over trimethoprim/polymyxin B eye drops, in terms of spectrum of activity and cost-effectiveness.

D. Clinical Presentation and Discussion: Proposal to identify preferred drugs in the therapeutic class of Ophthalmic Quinolones

Ophthalmic Quinolones

Drug(s) Affected: Ciloxan solution/ointment (ciprofloxacin), ciprofloxacin, Ocuflox (ofloxacin), ofloxacin, Quixin (levofloxacin), Vigamox (moxifloxacin), Zymar (gatifloxacin)

Steve Liles, PharmD, Provider Synergies; Robert Correia, PharmD, NYS Department of Health, Office of Medicaid Management (DOH/OMM)

Dr. Liles provided an overview of the drugs included in the ophthalmic quinolone review, including indications, in vitro susceptibility, effectiveness, use in special populations, adverse reactions, dosage forms and dosing. He discussed the differences in the second, third and fourth generation products with respect to indications and susceptibility, including susceptibility of resistant organisms. He discussed comparative trials of ocular penetration of the different products and noted that the results were not representative of clinical outcomes. In closing, he discussed the American Optometric Association (AOA) and the American Academy of Ophthalmology (AAO) practice guidelines for bacterial conjunctivitis.

Dr. Correia provided the Department's clinical review for this category. He discussed the value of these medications as alternative therapy in cases of intolerance or resistance to other antibiotics, and reemphasized the danger of overuse, leading to resistance. He explained the indications for the different products with regard to the generation (second, third and fourth), the spectrum of activity, the dosing and the duration of therapy. He discussed conflicting clinical studies with regard to corneal healing. He also indicated that there is currently no available evidence that corneal penetration and aqueous humor concentration of these medications produce any difference in actual clinical outcomes. He concluded that all of the available ophthalmic quinolones are effective. Given the identified overall differential in spectrum of activity between second generation versus third and fourth generation drugs, both of these groups should be represented on the preferred drug list.

A committee member commented on the marketing of this class of drugs, indicating that while the ophthalmic quinolones may have a place in therapy for more specific ocular problems, generic versions of some non-quinolone ophthalmic drops are also very effective for broad spectrum coverage. He also noted that in his opinion, the degree of resistance to these medications is proportional to how often they are used.

E. Clinical Presentation and Discussion: Proposal to identify preferred drugs in the therapeutic class of Otic Quinolones

Otic Quinolones

Drug(s) Affected: Cipro HC (ciprofloxacin/hydrocortisone), Ciprodex (ciprofloxacin/dexamethasone), Floxin (ofloxacin)

Steve Liles, PharmD, Provider Synergies; Robert Correia, PharmD, (DOH/OMM)

Dr. Liles provided an overview of otic quinolones including the indications, efficacy, pharmacokinetics, adverse reactions, dosage forms and dosing. He summarized clinical trials of these medications for acute and chronic otitis media with tubes (OMT), acute otitis externa (AOE), and chronic suppurative otitis media (CSOM). He reviewed the use of these medications in pediatrics and pregnancy, and reviewed the American Academy of Otolaryngology - Head and Neck Surgery Foundation Treatment Guidelines for AOE as well as guidelines for the treatment of AOMT and CSOM. He also discussed a meta-analysis for AOE, which included antiseptic, quinolone, and non-quinolone agents and agents containing a steroid.

Dr. Correia provided the Department's clinical review for this category of drugs. He reiterated the differences between the products with regard to the indications, sterility of product, dosing, viscosity of suspension and inclusion of a steroid component. He concluded that all three products are effective and may have subtle differences for particular patient populations with none demonstrating an overall advantage.

Committee discussion included the significance of the steroid component, the role of these medications, and the potential value of conducting a utilization review for both ophthalmic and otic quinolones.

F. Clinical Presentation and Discussion: Proposal to identify preferred drugs in the therapeutic class of Ophthalmic Antihistamines

Ophthalmic Antihistamines

Drug(s) Affected: Elestat (epinastine), Emadine (emedastine), ketotifen, Optivar (azelastine), Patanol (olopatadine), Zaditor (ketotifen)

Steve Liles, PharmD, Provider Synergies; Robert Correia, PharmD, (DOH/OMM)

Dr. Liles provided an overview of the pharmacology of these medications including their antihistamine and mast cell stabilizing properties. He discussed indications, pharmacokinetics, adverse reactions, dosage forms and dosing. He reviewed AOA and AAO clinical guidelines for allergic conjunctivitis. Dr. Liles noted that clinical studies of these medications compare different outcomes and are often conflicting. Many of the studies evaluate the efficacy of a single drop of medication used to treat the artificially induced symptoms of a conjunctival allergen challenge. Results indicate that products with mast cell stabilizing properties may have slightly better patient outcomes.

Dr. Correia provided the Department's clinical review for this drug category. He clarified the relevance of the subtle differences in FDA labeled indications with regard to itching versus other signs and symptoms and noted that relief of symptoms based on antihistamine and mast cell stabilization seems to be a class effect. He noted that olopatadine and emedastine have the same broad indication (signs and symptoms of allergic conjunctivitis), yet emedastine has only an antihistamine effect. Dr. Correia noted similarities in dosing and discussed the relevance of pregnancy category. In conclusion, Dr. Correia stated that any of the five products are effective for the treatment of allergic conjunctivitis with none of the drugs demonstrating overall advantages, but there may be a potential therapeutic advantage to the four products which have antihistamine and mast cell stabilizing properties as recognized in treatment guidelines.

A committee member asked for clarification on the number of products in the category with mast cell stabilizing properties. Dr. Correia indicated that four of the five drugs in the category have this property.

G. Clinical Presentation and Discussion: Proposal to identify preferred drugs in the therapeutic class of Immunomodulators (Injectable)

Immunomodulators (Injectable)

Drug(s) Affected: Enbrel (etanercept), Humira (adalimumab), Kineret (anakinra)

Gerald Gartlehner, MD, MPH, Oregon Health & Science University, Evidence-based Practice Center (OHSU EPC); Steve Liles, PharmD, Provider Synergies; Robert Correia, PharmD, (DOH/OMM)

Dr. Gartlehner presented the summary of the OHSU review of immunomodulators and discussed the outcomes of key areas of inquiries based on findings from clinical trials, including head-to-head trials. He provided the outcomes of studies comparing efficacy and effectiveness, tolerability, adverse events, safety and efficacy within certain subgroups. He noted that while there are no double-blind randomized trials comparing the injectable immunomodulators, adjusted indirect comparisons suggest that etanercept and adalimumab have greater efficacy than anakinra for the treatment of rheumatoid arthritis (RA). He also noted that while the immunomodulators are highly effective for the treatment of ankylosing spondylitis (AS), psoriatic arthritis (PsA), and juvenile rheumatoid arthritis (JRA), evidence is lacking to draw conclusions about comparative effectiveness.

Dr. Liles discussed the pharmacology of the medications in the review. He explained that although etanercept and adalimumab are anti-TNFα agents and anakinra is an IL-1 receptor antagonist, both exert activity by blocking pro-inflammatory cytokines. He reviewed the indications, pharmacokinetics, warnings, contraindications, drug interactions, adverse reactions, dosage forms, dosing and use in special populations (pediatrics, pregnancy). He briefly reviewed several treatment guidelines including the American College of Rheumatology (ACR) clinical guidelines for the treatment of RA and the ASAS (international society of experts in the field of spondyloarthritis) clinical guidelines for the treatment of AS. He noted that the drugs in the review have similar adverse reaction profiles and all carry significant warnings and contraindications.

Dr. Correia provided the Department's clinical review for this category. He reiterated that the drugs in this review are all covered in the Medicaid pharmacy program, whether they are recommended as preferred or non-preferred. He discussed the indications for the drugs and noted the dosage forms and the differences in frequency of administration. He indicated that very little direct comparative evidence is available and the new evidence mentioned in public comment is not comparative. He discussed indirect and adjusted comparisons for these medications noting that while any of the three products are effective for the treatment of RA, the anti-TNFα agents seem to be more effective than anakinra, have additional indications and are associated with more serious adverse effects.

The committee raised several issues regarding the increased incidence of lymphoma, questioning the incidence in the different diagnoses, gender prevalence and incidence in RA patients in general, with or without immunomodulators. It was noted that the incidence is low and the data is dependent on the quantity and quality of adverse event reporting and post-marketing evidence.

Another committee member noted that in clinical practice, the anti-TNFα drugs may have a higher incidence of adverse effects because they are more highly utilized and while the clinical experience is anecdotal, it seems to be consistent with available evidence.

A committee member noted that tuberculosis and hepatitis B adverse reactions can often be prevented with proper screening.

H. Review of the Cholesterol Absorption Inhibitors (CAIs) therapeutic class

Steve Liles, PharmD, Provider Synergies; Anthony Merola, RPh, MBA, (DOH/OMM)

Dr. Liles presented a brief overview of the CAI class, specifically ezetimibe (Zetia), including indications, efficacy, pharmacokinetics, drug interactions, adverse reactions, dosage forms and dosing. As there is only one drug in this class, there is no comparative data within the class, and there is no data for clinical outcomes.

Mr. Merola indicated the purpose of the review of the CAIs therapeutic class is to determine if the class should be included in the Preferred Drug Program (PDP). He clarified that Zetia (ezetimibe) is currently covered by Medicaid and Vytorin (simvaststin and ezetimibe) was added to the PDP as a preferred drug in March, 2006. The addition of the CAI class to the PDP may eliminate uncertainty with regard to the availability of ezetimibe. In addition, Mr. Merola indicated that this will allow the Committee to address any newly approved drugs that fall into this therapeutic class using the procedure developed in June 2006 for newly approved drugs subject to the PDP.

A Committee member noted that statins are available generically and are being prescribed in higher doses, and asked if there was efficacy data on high dose statins versus a statin plus ezetimibe. Drs. Liles and Correia indicated that Vytorin (the combination product which contains ezetimibe) is highly effective in lowering LDL, even compared to the high dose statins, and ezetimibe can be used in combination with any of the statins to achieve that effect.

A Committee member indicated that because high dose statin therapy may result in more adverse effects, it is advantageous to have a drug like ezetimibe to add in combination for additional lipid lowering effect.

It was also noted by a Committee member that patients with HIV are limited in what statins they can use, and Zetia (ezetimibe) combination therapy has shown benefit.

I. Executive Session:

The Committee recessed the public session at 12:15 P.M. to go into executive session for review of financial information relating to the determination of preferred drugs in the following classes: Ophthalmic Quinolones, Otic Quinolones, Ophthalmic Antihistamines, Immunomodulators (Injectable), and Cholesterol Absorption Inhibitors. No official action was taken in the executive session. The executive session was recessed at 1:30 P.M..

J. Recommendations of the Pharmacy and Therapeutics Committee:

The following recommendations developed by the P&T Committee are to be submitted to the Commissioner of Health for final determination.

Description of Recommendations	Commissioner's Final Decision
Proposal: Identification of preferred drugs in the category of Ophthalmic Quinolones A. Based on the submitted or presented clinical information and on the financial information provided during the executive session, the Committee unanimously recommended the following: Preferred Drugs ciprofloxacin solution, ofloxacin solution, Vigamox Non-preferred Drugs Ciloxan solution, Ciloxan ointment, Ocuflox, Quixin, Zymar B.The Committee unanimously recommended the following clinical questions be used as the basis for approving use of the non-preferred drug: Q: Has your patient experienced treatment failure with a preferred ophthalmic quinolone? Q: Has your patient experienced an adverse drug reaction with a preferred ophthalmic quinolone? Q: Is there a documented history of successful therapeutic control with a non-preferred ophthalmic quinolone and transition to a preferred ophthalmic quinolone is medically contraindicated?	Approved as Recommended
Proposal: Identification of preferred drugs in the category of Otic Quinolones A. Based on the submitted or presented clinical information and on the financial information provided during the executive session, the Committee unanimously recommended the following: Preferred Drugs Ciprodex, Floxin Non-preferred Drug Cipro HC B. The Committee unanimously recommended the standard clinical questions be used in the prior authorization review process.	Approved as Recommended
Proposal: Identification of preferred drugs in the category of Ophthalmic Antihistamines A. Based on the submitted or presented clinical information and on the financial information provided during the executive session, the Committee unanimously recommended the following: Preferred Drug Patanol Non-preferred Drugs Elestat, Emadine, ketotifen, Optivar, Zaditor B. The Committee unanimously recommended the standard clinical questions be used in the prior authorization review process.	Approved as Recommended
Proposal: Identification of preferred drugs in the category of Immunomodulators (Injectable) A. Based on the submitted or presented clinical information and on the financial information provided during the executive session, the Committee unanimously recommended the following: Preferred Drugs Enbrel, Humira Non-preferred Drug Kineret B. The Committee unanimously recommended the standard clinical questions be used in the prior authorization review process.	Approved as Recommended
Proposal: Review of the Cholesterol Absorption Inhibitors (CAIs) therapeutic class The Committee unanimously recommended that the Cholesterol Absorption Inhibitor (CAI) therapeutic class be included in the Preferred Drug Program. Based on the submitted or presented clinical information and on the financial information provided during the executive session, the Committee unanimously recommended the following: Preferred Drug Zetia Non-preferred Drug None	Approved as Recommended

K. Additional Discussion:

Dr. Martin expressed appreciation to the Committee, and on behalf of the Committee to State staff and the public for making the Pharmacy and Therapeutics Committee meetings possible.

Ms. Jones announced that the next Medicaid Pharmacy and Therapeutics Committee meeting is tentatively scheduled for the Spring of 2007, and the agenda will be posted on the DOH website 30 days in advance of the meeting date.

The meeting adjourned at 1:40 PM.

Meeting Summary Posted 1/16/07

L. Final Determinations:

The Commissioner has determined that Medicaid will require prior authorization under the Preferred Drug Program (PDP) for non-preferred drugs, as listed above, in the following classes: Ophthalmic Quinolones, Otic Quinolones, Ophthalmic Antihistamines, Immunomodulators (injectable) and Cholesterol Absorption Inhibitors (CAIs). Preferred drugs will not require prior authorization.

The impacts of this final determination are as follows:

1. State Public Health Population:
   • Minimal effects as a large majority of Medicaid patients currently utilize those drugs which have been determined to be preferred.
   • Use of prior authorization for non-preferred products encourages use of more cost effective drugs within the same therapeutic class when appropriate.
2. Program Providers:
   • Limited additional time and effort will be required by prescribers to complete the prior authorization process for non-preferred drugs.
3. Fiscal Impact to State Health Program:
   • Through the changes in utilization to more cost effective drugs, and the receipt of supplemental rebates from pharmaceutical manufacturers, annual savings for these categories of drugs under the Preferred Drug Program are estimated at $11.0 M.

Final Determinations Posted 3/16/2007