Pharmacy and Therapeutics Committee Meeting Summary - September 18, 2008

Agenda and Introduction

The Medicaid Pharmacy & Therapeutics Committee met on Thursday, September 18, 2008 from 8:30 a.m. to 4:00 p.m. in Meeting Room 6, Concourse, Empire State Plaza, Albany, New York.

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. Rosti, Robert, PharmD, Medical Science Liaison, EMD Serono, Rockland, MA
  2. DiFiore, Michael, PharmD, Medical Science Liaison, Biogen-IDEC, Cambridge, MA
  3. Su, Wendy, PhD, Regional Account Manager, Teva Neuroscience, Kansas City, MO
  4. Rhodes, Lori, Program Coordinator, The National MS Society Upstate NY Chapter, Albany, NY
  5. Baran, Daniel, MD, Senior Medical Director, Merck & Co., Shrewsbury, MA
  6. Leibowitz, Jonas, MD, Private Practice, Yonkers, NY
  7. Eggleston, Steven T. PharmD, Regional Medical Scientist, GlaxoSmithKline, Albany, NY
  8. DeLuca, Michael, PharmD, MBA, Sr. Manager of Medical Information, Sepracor Inc., Marlborough, MA
  9. Gall, Rebecca, MD, Medical Science Liaison, Schering-Plough, Uxbridge, MA
  10. Irwin, Robert, MD, Pulmonary & Critical Care Services, Troy, NY
  11. Dac-Korytko, Ia, MD, Senior Regional Scientific Manager, AstraZeneca, Buffalo, NY
  12. Paeglow, Robert, MD, Medical Director, Koinonia Primary Care, Albany, NY
  13. Behanick, Judith, RN, Asthma Coalition of the Southern Tier, Johnson City, NY
  14. Papariello, Anthony, PharmD, Regional Medical Scientist, GlaxoSmithKline, Hanover, NJ
  15. Sanders, Alan, MD, Upstate Infectious Diseases Associates, Albany, NY
  16. Stern, Leonard, MD, FACP, FASN, Associate Clinical Professor of Medicine, Columbia University, College of Physicians & Surgeons Medical Director, New York, NY
  17. Rosen, Herman, MD, Clinical Professor of Medicine, New York Presbyterian Hospital, Weill Cornell Medical Center, New York, NY
  18. Goldman, Donna, MD, Senior Medical Liaison, Roche, Nutley, NJ
  19. Sheffield, Tim, Senior Scientific Liaison, Astellas Pharma US, Midlothian, VA
  20. Clarke, Sherwanna, PharmD, Government Regional Clinical Executive, Abbott, Marietta, GA
  21. Masamitsu, Michael, PharmD, Senior Regional Medical Liaison, Amgen, Florence, MA
  22. Konev, Anton, Senior Legislative Assistant to Assemblyman Peter Rivera, Bronx, NY

C. Key issues raised by interested parties and the Pharmacy and Therapeutics Committee pertaining to the clinical review of the following therapeutic classes:

Public comments:

Multiple Sclerosis Agents:

  • The Committee was asked to consider information regarding clinical trial results including indications, efficacy in preventing disability progression, reducing the frequency of relapses and brain lesions on MRI, efficacy over time, mechanism of action, safety, adverse events, precautions, warnings, use in patients experiencing clinically isolated syndrome, convenience in administration and dosing, and pregnancy category. The Committee was also asked to consider the National Multiple Sclerosis Society Disease Management Consensus Statement, and the importance of maintaining access to medications early in the disease process for individualized courses of treatment.

Dipeptidyl Peptidase-4 (DPP- 4) Inhibitors:

  • The Committee was asked to consider information regarding clinical trial results including the mechanism of action of the DPP-4s, indications, efficacy in lowering A1C as monotherapy and in combination with other oral hypoglycemic agents, safety, use in renal insufficiency, renal failure, and congestive heart failure, and adverse events. The Committee was also asked to consider the DPP-4/metformin combination product in terms of efficacy and indications, as well as the black box warning for the metformin component.

Beta2 Adrenergic Agents - Inhaled Short Acting (SABA):

  • The Committee was asked to consider information regarding clinical trial results including efficacy, dosing and dosing frequency, beta-mediated side effects, pharmacokinetics, hospital admission rates, use in exercise-induced bronchospasm (EIB), as well as the phase-out of albuterol inhalers with chlorofluorocarbon (CFC) propellant and the availability of short-acting inhaled beta agonists with hydrofluoroalkane (HFA) propellant.

Beta 2 Adrenergic Agents - Inhaled Long Acting (LABA):

  • The Committee was asked to consider information regarding clinical trial results including the place in therapy and the black box warning for LABAs, adverse events when used with and without inhaled corticosteroids, use in pediatrics, and use in EIB and chronic obstructive pulmonary disease (COPD).

Inhaled Corticosteroids:

  • The Committee was asked to consider information regarding clinical trial results including indications, dosing, adverse events, use in pediatrics, the effect on growth velocity in children, use in pregnancy, use of rescue medications, and the different inhalation devices. The Committee was also asked to consider clinical information regarding the combination inhaled corticosteroid/long acting beta2 agonist products including indications, efficacy, safety, onset of action, use in special populations such as African Americans and pediatrics, use in COPD, compliance and adherence, the boxed warning for products containing a LABA, and use of rescue medications.

Leukotriene Modifiers:

  • The Committee was asked to consider information regarding clinical trial results including indications, efficacy, adherence and compliance with "controller" medications, and the updated product information for montelukast with regard to adverse reactions.

Anti-Virals:

  • The Committee was asked to consider information regarding clinical trial results for Valtrex (valacyclovir) including indications, safety, dosing, heterosexual disease transmission, and use in patients co-infected with HIV.

Phosphate Binders/Regulators:

  • The Committee was asked to consider information regarding clinical trial results including efficacy, safety, adverse events, the number of tablets per dose, the effects of hyperphosphatemia and the role of phosphate binders in end stage renal disease (ESRD), and the metabolic effects of the different phosphate binder formulations.

Pegylated Interferons:

  • The Committee was asked to consider information regarding clinical trial results including indications, length of treatment based on genotype, response based on ribavirin dosing, and predictors of response, such as rapid virological response (RVR), and early virological response (EVR).

Topical Immunomodulators:

  • The Committee was asked to consider information regarding clinical trial results including indications (adult and pediatric), place in therapy, efficacy, onset of action, adverse events, safety, pharmacokinetics, and degree of systemic exposure.

Injectable Immunomodulators:

  • The Committee was asked to consider information regarding clinical trial results including indications (adult and pediatric), mechanism of action, affect on neutralizing antibodies and cell lysis, efficacy with and without methotrexate, adverse events, dosing, post-marketing experience, and safety, including the September 4th FDA alert regarding invasive fungal infections.

Pharmacy and Therapeutics Committee Comments:

  • A Committee member and presenter discussed the incidence of pancreatitis, gastroparesis, and nausea and vomiting with sitagliptin.
  • A Committee member and presenter discussed the measurement and clinical relevance of first dose efficacy for levalbuterol solution.
  • A Committee member and presenter discussed a meta-analysis with regard to the use of LABAs and inhaled corticosteroids, particularly noting the rate of adverse events in the African American population.
  • A presenter speaking on behalf of budesonide/formoterol noted, in response to a question from a Committee member, that adrenal suppression was not reported with doses up to four times the recommended dose, and there was no data with regard to cataracts.
  • A Committee member asked a physician presenter speaking on behalf of budesonide/formoterol when he would use that medication rather than fluticasone/salmeterol and the presenter indicated that he uses it in patients who overuse albuterol inhalers, and his patients appear to prefer the fast onset of action which, in his opinion, improves compliance.
  • With regard to the phosphate binders/regulators, a Committee member asked for clarification regarding the increased cardiovascular risk in renal patients caused by calcium load versus other comorbid conditions such as increased lipids. The presenter indicated that an impaired mineral balance, including the inability to excrete calcium, is related to increased calcium intake and vascular calcification which is considered an independent risk factor for cardiovascular disease.
  • A Committee member reiterated that the Pharmacy and Therapeutics Committee makes recommendations to the Commissioner of Health, who then renders final determinations based on the recommendations. Another committee member reiterated the difference between aborting and preventing an asthma exacerbation and the importance of the inhaled corticosteroids in preventing exacerbations.

D. Clinical Presentation and Discussion

Marian McDonagh, PharmD, Oregon Health & Sciences University, Evidence-based Practice Center (OHSU EPC); Barbara Rogler, PharmD, MS, First Health Services Corporation (FHSC); Robert Correia, PharmD, NYS Department of Health, Office of Health Insurance Programs (DOH/OHIP)

Proposal to identify preferred drugs in the therapeutic class of Multiple Sclerosis Agents

Drugs Affected: Avonex (interferon beta-1a), Betaseron (interferon beta-1b), Copaxone (glatiramer acetate), Rebif (interferon beta-1a)

Dr. McDonagh presented an overview of the OHSU Drug Effectiveness Review Project (DERP) Drug Class Review on Disease-Modifying Drugs for Multiple Sclerosis dated July, 2007. She presented data from placebo controlled and head-to-head trials on the effectiveness of interferons as a group in relapsing-remitting multiple sclerosis (RRMS) as well as data on the appearance of neutralizing antibodies with the interferons. She presented data from placebo controlled trials and meta-analyses regarding the use of glatiramer acetate in RRMS. She also discussed the limited data available for the treatment of primary-progressive, progressive-relapsing, and secondary-progressive MS. She discussed the use of the interferon-betas in reducing the conversion of clinically isolated syndrome to clinically definitive MS. She discussed rates of adverse events both comparatively among the interferon-betas and for glatiramer. She also noted the lack of comparative data for use of these drugs in special populations, specifically in African Americans and pregnant women.

Dr. Rogler presented an overview of the MS agents noting each drug's indications and dosage. She presented background information on MS and explained the clinical subtypes which define the natural progression of MS. She described the goal of disease modifying therapy and mentioned the National Multiple Sclerosis Society (NMSS) Management Consensus. She discussed the EVIDENCE trial and the Proof Study. She concluded by noting factors which may affect therapy selection, including patient preference, adherence to therapy, tolerability and ease and frequency of medication administration. She also noted that the drugs in this class are not interchangeable, and are not available generically.

Dr. Correia pointed out that there are contradictory conclusions between the comparative versus the placebo-controlled trials as noted within and subsequent to the OHSU report, and confounding elements such as different patient demographics between studies, different types of primary outcomes and assessment tools for those outcomes, or non-comparable doses of drugs. He noted that baseline level of disease or disability and how changes from that baseline are measured may impact study results. He provided examples of outcomes that may be evaluated such as conversion to persistent disease, physiological findings from scans, rate of progression of disability, relapse rate, and incidence, type, or severity of adverse drug effects. He noted that although MS is predominantly a chronic, long-term, progressive disease, there are few long term studies, many of which are only approximately two years in length, and the length of a study is critical in considering whether comparative or other outcomes are truly clinically significant or even relevant to the long term prognosis.

He noted that the interferons and glatiramer are the two types of drugs used to treat MS and explained the different routes and frequencies of administration, noting apparent trade-offs when choosing between these drugs. For example, he noted with the interferons, the subcutaneous formulations seem to generate more neutralizing antibodies than the intramuscular formulation, but the significance of this is controversial, and doesn't seem to translate into decreased drug efficacy, although there is limited data that this may increase relapse rates at 3 to 4 years. He also discussed trade-offs between drugs with regard to adverse effects, for example, flu-like syndrome versus injection site reactions and fever. He discussed that glatiramer has more evidence versus relapse and less evidence versus disease progression for different types of MS, but it is the only agent which is currently pregnancy category B. He also noted there was no other evidence of comparative differences between the drugs in other specific patient populations. He concluded that overall, there is no evidence that any of these agents are better overall for all patients, and each may demonstrate favorable efficacy or tolerability for different patients or patient groups.

Review of the Dipeptidyl Peptidase-4 (DPP- 4) Inhibitor therapeutic class for inclusion to the Preferred Drug Program (PDP)

Drugs Affected: Drug Affected: Januvia (sitagliptin), Janumet (sitagliptin/metformin HCL)

Dr. Rogler provided background information on the incretins and described the mode of action for glucagon-like peptide-1 (GLP-1) and glucose dependent insulinotropic polypeptide (GIP). She provided information on sitagliptin and sitagliptin/metformin, including mechanism of action, indications, pharmacodynamics, pharmacokinetics, drug interactions, contraindications, warnings, adverse reactions and effect on body weight. She spoke about the use of the medications in special populations including pregnant women, nursing mothers, pediatrics and geriatrics. She noted the black box warning for the combination product due to the metformin component. She discussed dosage and administration, including dosing in renal insufficiency.

Dr. Correia noted there is only one DPP-4 drug in this class, available either alone or in a combination product with metformin, therefore there is no basis for a comparative review at this time. He indicated this drug class represents an ongoing area of research, with several new drugs in the pipeline. Establishing the therapeutic class within the PDP will allow the Committee to address any newly approved drugs as they become available.

Re-review of Preferred Drug Program therapeutic classes

1. Re-review of the Beta 2 Adrenergic Agents - Inhaled Short Acting class

Drugs Affected: Accuneb (albuterol), albuterol, Alupent (metaproterenol), Maxair Autohaler (pirbuterol), metaproterenol, ProAir HFA (albuterol), Proventil (albuterol), Proventil HFA (albuterol), Ventolin HFA (albuterol), Xopenex (levalbuterol), Xopenex HFA (levalbuterol)

Dr. Rogler reiterated the Food & Drug Administration (FDA) Public Health Advisory dated May 30, 2008 regarding chlorofluorocarbon (CFC) propelled albuterol inhalers and the December 31, 2008 deadline for transition to albuterol inhalers with the hydrofluoroalkane (HFA) propellant. She noted the Global Initiative for Asthma (GINA) guidelines which reflect a change in focus from asthma severity to asthma control. She also noted the National Asthma Education and Prevention Panel summary of the third report of the Expert Panel (EPR-3) that emphasizes the importance of asthma control and identifies asthma severity as the intrinsic intensity of the disease process.

Dr. Correia noted that good quality comparative new evidence for the short acting beta agonists is lacking. He discussed an open-label 2-week study of nebulized therapy administered to asthma and COPD hospital inpatients, comparing standard dosing of levalbuterol to variable dosing of racemic albuterol. He noted the primary endpoint was total number of nebulizations, including both scheduled and rescue treatments during the hospital stay. He explained the primary outcome was presented as significantly less total nebulizations and scheduled nebulizations for levalbuterol, based only on the statistical median measurement, even though the actual difference in this median measurement was two nebulizations over the course of the hospital stay, or ten versus twelve scheduled nebulizations, with no difference in use of rescue treatments. He also noted there was no statistically significant difference in median total number of nebulizations for either asthma or COPD patient groups individually. He explained that the evaluation of beta-mediated adverse effects was a secondary endpoint dependent upon patient recall, and noted that this assessment may have been affected by the fact that neither patients nor researchers were blinded to which drug was given. He also noted other potential sources of bias within the study, and noted the patient clinical setting and circumstances are not representative of the Medicaid pharmacy program. He indicated there was no difference between levalbuterol and racemic albuterol for other secondary endpoints such as pulmonary function, length of hospital stay, or time to discharge. He concluded there is a lack of good new comparative information for this drug class since last reviewed, and inadequate evidence to justify preferential availability of any one product.

2. Re-review of the Beta2 Adrenergic Agents - Inhaled Long Acting class

Drug Affected: Brovana (arformoterol), Foradil (formoterol), Perforomist (formoterol), Serevent Diskus (salmeterol)

Dr. Rogler spoke about the FDA Public Health Advisory dated February 29, 2008 regarding proper use of Foradil capsules and the FDA Update dated March 5, 2008 regarding the assessment of risks of the LABAs and input from the Pediatric Advisory Committee (PAC). She also noted again, as with the SABAs, the National Asthma Education and Prevention Panel summary of the third report of the Expert Panel (EPR-3).

Dr. Correia noted the significant new information applies to the entire drug class, as well as any combination products which contain a long-acting beta agonist, and is related to safety concerns, particularly for use in asthma. He concluded no new differential information has been found to indicate any of these products demonstrate an overall clinical advantage.

Several Committee members, Dr. Rogler and Dr. Correia discussed the onset of action of the LABAs with regard to patient perception and compliance, and also the importance of using maintenance medications on a regular basis.

3. Re-review of the Inhaled Anticholinergic therapeutic class

Drugs Affected: Atrovent HFA (ipratropium), Combivent (ipratropium/albuterol), Duoneb (ipratropium/albuterol), ipratropium, ipratropium/albuterol, Spiriva (tiotropium)

Dr. Rogler mentioned the UPLIFT Study, noting that the results have not yet been published. She discussed the FDA Public Health Advisory dated February 29, 2008 regarding proper use of Spiriva capsules and the FDA Early Communication dated March 18, 2008 regarding a possible increased risk of stroke in patients on tiotropium therapy. She noted further recommendations from the FDA can be expected with the release of the UPLIFT study data.

Dr. Correia noted little, if any, definitive new clinical information, and a lack of comparative evidence for the drugs in this class. He indicated there has been new information related to safety issues for these drugs but it seems that there may be an overall issue of cardiovascular impact for the entire drug class, including possible increased risk of stroke for tiotropium, and possible risk for cardiovascular death with ipratropium, although in both cases, information is preliminary and inconclusive. He concluded that different products may be more appropriate at different points of disease process or progression, but there has been no new evidence since the last review to support overall clinical superiority of any one these products.

4. Re-review of the Inhaled Corticosteroid therapeutic class

Drugs Affected: Advair Diskus (fluticasone/salmeterol), Advair HFA (fluticasone/salmeterol), Aerobid/Aerobid-M (flunisolide), Asmanex (mometasone), Azmacort (triamcinolone), Flovent Diskus (fluticasone), Flovent HFA (fluticasone), Pulmicort Flexhaler (budesonide), Qvar (beclomethasone), Symbicort (budesonide/formoterol)

Dr. Rogler discussed an FDA Update from January 2008 in which the FDA requested additional information on the safety of LABAs used in the treatment of asthma from the manufacturers of Advair and Symbicort. She discussed a new pediatric indication for Asmanex and safety labeling revisions for Asmanex emphasizing warnings and precautions associated with its use. She discussed a new indication for Advair for the reduction of COPD exacerbations in adults, and safety labeling revisions as well to warn of both drug interactions with salmeterol and the risk of pneumonia in patients with COPD. She also noted both Advair and Symbicort received approval for dose counters.

Dr. Correia reiterated the expanded age indication and safety labeling revisions for the Asmanex product, and noted the other products in the class with labeling for children as young as four years of age. He reiterated the new indication for Advair for COPD, as well as the new warning for risk of pneumonia with Advair for COPD patients. He noted the new labeling for the Advair combination products regarding interactions with cytochrome P-450 (CYP-450) inhibitors and salmeterol and further explained that in general, the steroid component of these products is also metabolized by CYP-450, and co-administration has produced elevated serum steroid levels, therefore labeling for any of the steroid inhalers already includes a caution for co-administration of potent CYP-450 inhibitors. He concluded there is little new good quality comparative information in this drug class, and although different products may be more appropriate at different points of disease process or progression, there is not adequate new evidence of clinical superiority for any one these products to justify preferential availability.

5. Re-review of the Leukotriene Modifier therapeutic class

Drugs Affected: Accolate (zafirlukast), Singulair (montelukast)

Dr. Rogler noted the FDA Communication about the Ongoing Safety Review of Montelukast (Singulair) dated March 27, 2008, noting that the FDA estimates it will take nine months to complete.

Dr. Correia reiterated the new potential safety issue raised by the FDA for montelukast, noting the issue remains under investigation and is unresolved at this time. He concluded that he found no new comparative evidence and little new clinical information, and found nothing new to differentiate the drugs in this class.

A Committee member asked for further information on the montelukast safety warning, and Dr. Correia indicated that the studies are ongoing at this time.

6. Re-review of the Anti-Viral therapeutic class

Drugs Affected: acyclovir, famciclovir, Famvir (famciclovir), Valtrex (valacyclovir), Zovirax (acyclovir)

Dr. Rogler noted the two new indications for Valtrex.

Dr. Correia indicated that now both famciclovir and valacyclovir have indications for treatment of cold sores, and both acyclovir and valacyclovir have indications for treatment of chickenpox. He reiterated the Federal CDC Treatment Guidelines for the Treatment of Sexually Transmitted Diseases which state that all 3 drugs in this class may be used to treat initial and recurrent genital herpes, as well as provide suppressive therapy for both immunocompetent and HIV-infected patients. He noted that again this year it was stated that valacyclovir has been proven to decrease herpes transmission to uninfected heterosexual adults and discordant couples, with a 75% reduction in risk. He emphasized that this data is from a study that only included monogamous, heterosexual couples, who were not HIV infected, and only for 8 months of treatment. He also noted the results have been submitted as high percentages of risk reduction, but this is really derived from an actual decrease of disease transmission of only 1.7%. Dr. Correia restated the clarification again this year due to the potential for public harm as the data on herpes transmission in discordant couples does not include other populations, especially not high-risk or HIV co-infected populations.

Dr. Correia spoke about the dosing of the different drugs in the class according to current CDC guidelines, indicating that differences in dosing may not be as significant as presented, and further noting that he is not aware of evidence which demonstrates increased compliance or adherence with once daily versus twice daily dosing. He concluded that no new comparative evidence was found to differentiate effectiveness between the three drugs, and all three drugs are effective and any one may have advantages for a specific use or patient population, but none significantly overall.

A Committee member asked the value of using an antiviral medication for cold sores, and it was noted the medication may decrease the duration of the outbreak.

7. Re-review of the Anti-Fungal therapeutic class

Drugs Affected: ciclopirox, Grifulvin V (griseofulvin), Gris-PEG (griseofulvin), griseofulvin, itraconazole, Lamisil (terbinafine), Penlac (ciclopirox), Sporanox (itraconazole), terbinafine

Dr. Rogler indicated that she found no new clinical information since the last review of this therapeutic class.

Dr. Correia noted that he found no new clinical evidence to change the previous assessment of the drugs in this class. He reiterated that any of the three oral products are effective and may have advantages for particular infections or patient populations, with none of these drugs demonstrating overall advantages for all cases. He also noted the topical preparations are inferior and of questionable effectiveness in resolving onychomycosis compared to the oral agents.

8. Re-review of the Phosphate Binder/Regulator therapeutic class

Drugs Affected: Fosrenol (lanthanum), Phoslo (calcium acetate), Renagel (sevelamer HCL), Renvela (sevelamer carbonate)

Dr. Rogler provided information on the new product in the class, sevelamer carbonate (Renvela), including mechanism of action, dosage, warnings, adverse effects, and pregnancy category. She noted that in clinical trials, sevelamer carbonate was shown to increase serum bicarbonate levels and may minimize the incidence of acidosis. She also noted that during a crossover study, sevelamer carbonate was shown to be equivalent to sevelamer HCL, and in patients taking sevelamer HCL, the dose of sevelamer carbonate is the same.

Dr. Correia reiterated the new version of sevelamer (carbonate) has been shown to be equivalent to the previous sevelamer product (sevelamer HCL) in reducing serum phosphorus levels and noted that both lanthanum and sevelamer are now available in a carbonate form. He indicated the four drugs under consideration represent two treatment approaches, calcium-based or non-calcium based phosphate binding. He reiterated that each of the drugs has individual benefits or risks depending on stage of disease or patient comorbidity, and that no new comparative evidence was found to differentiate between the four products. He concluded that any of the four drugs may have advantages or be preferable at different stages of disease progression, with none of these drugs demonstrating overall advantages at all stages or in all situations.

9. Re-review of the Pegylated Interferon therapeutic class

Drugs Affected: PEG-Intron (peginterferon alfa-2b), Pegasys (peginterferon alfa-2a)

Dr. Rogler discussed the updated guidelines for the care of patients co-infected with HIV and hepatitis C virus (HCV). She discussed the preferred treatment regimen including recommended duration of therapy based on genotype, and predictors for successful therapy. She also discussed the recommended treatment for acute HCV infection in HIV-positive patients. She discussed the PRESCO study which evaluated the predictors of HCV relapse in HIV/HCV co-infected patients treated with peginterferon alfa-2a plus ribavirin for distinct periods of time.

Dr. Correia noted that new clinical information for this drug class applies equally to either treatment. He noted that he found no good new comparative evidence to differentiate effectiveness between the two products, and there is still no published data to demonstrate either of these products is superior overall, although each may demonstrate preferential characteristics within specific sub-populations.

10. Re-review of the Topical Immunomodulator therapeutic class

Drugs Affected: Elidel (pimecrolimus), Protopic (tacrolimus)

Dr. Rogler spoke about the National Institute for Health and Clinical Excellence (NICE) guidelines which promote a stepwise approach for the management of atopic eczema in children less than twelve years of age. She noted the guidelines recommend reserving the topical immunomodulators as second line therapy in patients who do not respond to topical corticosteroids or when there is a serious risk of adverse events with their use.

Dr. Correia noted both pimecrolimus cream and tacrolimus ointment are indicated for the treatment of atopic dermatitis, but for different ranges of symptoms; mild to moderate versus moderate to severe. He concluded he found no new evidence to indicate that either of these products is safer or preferential overall.

11. Re-review of the Injectable Immunomodulator therapeutic class

Drugs Affected: Cimzia (certolizumab pegol), Enbrel (etanercept), Humira (adalimumab), Kineret (anakinra)

Dr. Rogler began her presentation with background information on a new product in this class, certolizumab pegol, noting it is the first pegylated tumor necrosis factor (TNF) blocker. She discussed indications, mechanism of action, dosage, adverse effects and precautions. She discussed two clinical trials evaluating certolizumab pegol, both in patients with moderate-to-severe Crohn's disease, to evaluate efficacy in adult patients, and noted there are currently no head-to-head trials with other immunomodulators that are indicated in the management of Crohn's disease. She discussed the two new indications for adalimumab, and a new boxed warning for etanercept related to the risk of infections and tuberculosis, which, she noted, is a class warning. She spoke about several new FDA communications, including investigations of lymphoma and other cancers with the use of TNF blockers in children and young adults, serious skin reactions (etanercept, adalimumab) and an enhanced warning for the class on the risk of developing opportunistic fungal infections.

Dr. Correia described the two main cytokine immune processes impacted by the biologic drugs under review, tumor necrosis factor (adalimumab, certolizumab, etanercept), and interleukin-1 (anakinra). He noted all are subcutaneous injections, with dosing daily, weekly, every other week, or monthly, depending on drug and indication. He noted the new drug in the class, certolizumab, is dosed every other week to start, then once monthly and is currently only indicated for Crohn's disease. He also noted there is a lack of comparative evidence between certolizumab and the other drugs in this class.

He explained there are new indications for individual drugs within the class which makes their labeling more similar, but also noted most of the new information pertains to additional or enhanced warnings which are apparent class effects for all the TNF antagonists, and he reiterated those warnings as noted by Dr. Rogler. He then reiterated each product's indications, and added that indirect evidence suggests the TNF antagonists adalimumab and etanercept seem to be more effective than anakinra, however they have also been associated with more serious adverse effects. He concluded no new comparative evidence was found to differentiate effectiveness between the four products.

E. 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: MS Agents, the DPP-4 Inhibitor, Short and Long-Acting Beta2 Adrenergic Agents, Inhaled Anticholinergics, InhaledCorticosteroids, Leukotriene Modifiers, and Anti-Virals. No official action was taken in the executive session. The executive session was recessed at 2:10 P.M.

The Committee recessed the public session at 2:40 P.M. to go into executive session for review of financial information relating to the determination of preferred drugs in the following classes: Anti- Fungals, Phosphate Binders/Regulators, Pegylated Interferons, Topical Immunomodulators, and Injectable Immunomodulators. No official action was taken in the executive session. The executive session was recessed at 3:00 P.M.

F. 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 RecommendationsCommissioner's Final Determination
Proposal: Identification of preferred drugs in the category of Multiple Sclerosis Agents

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
Avonex (interferon beta-1a), Betaseron (interferon beta-1b), Copaxone (glatiramer acetate), Rebif (interferon beta-1a)

Non-preferred Drugs
None

B. The Committee unanimously recommended the standard clinical questions be used as the basis for approving use of a non-preferred drug, should the Commissioner's final decision include a non-preferred drug.

  • Q: Has your patient experienced treatment failure with preferred drugs in the class?
  • Q: Has your patient experienced an adverse drug reaction with preferred drugs in the class?
  • Q: Is there a documented history of successful therapeutic control with a non-preferred drug and transition to a
    preferred drug is medically contraindicated?
Approved as Recommended
Proposal: Identification of preferred drugs in the category of Dipeptidyl Peptidase-4 (DPP-4) Inhibitors

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
Januvia (sitagliptin), Janumet (sitagliptin/metformin HCL)

Non-preferred Drugs
None

B. The Committee unanimously recommended the standard clinical questions be used as the basis for approving use of a non-preferred drug, should the Commissioner's final decision include a non-preferred drug.

Approved as Recommended
Proposal: Identification of preferred drugs in the category of Beta 2 Adrenergic Agents - Inhaled Short Acting

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
albuterol, Maxair Autohaler (pirbuterol), Ventolin HFA (albuterol)

Non-preferred Drugs
Accuneb (albuterol), Alupent (metaproterenol), metaproterenol, ProAir HFA (albuterol), Proventil HFA (albuterol), Xopenex solution (levalbuterol), Xopenex HFA (levalbuterol)

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 Beta 2 Adrenergic Agents - Inhaled Long Acting

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
Foradil (formoterol), Serevent Diskus (salmeterol)

Non-preferred Drugs
Brovana (arformoterol), Perforomist (formoterol)

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 Anticholinergics - Inhaled

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
Atrovent HFA (ipratropium), Combivent (ipratropium/albuterol), ipratropium, ipratropium/albuterol, Spiriva (tiotropium)

Non-preferred Drugs
Duoneb (ipratropium/albuterol)

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 Corticosteroids - Inhaled

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
Advair Diskus/Advair HFA (fluticasone/salmeterol), Asmanex (mometasone), Azmacort (triamcinolone), Flovent Diskus (fluticasone), Flovent HFA (fluticasone), Qvar (beclomethasone)

Non-preferred Drugs
Aerobid/Aerobid-M (flunisolide), Pulmicort Flexhaler (budesonide), Symbicort (budesonide/formoterol)

B. The Committee unanimously recommended the standard clinical questions be used in the prior authorization review process and again recommended one additional clinical question for specific product concerns related to pregnancy:

  • Q: Is this prior authorization request due to concerns related to pregnancy?
Approved as Recommended
Proposal: Identification of preferred drugs in the category of Leukotriene Modifiers

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
Accolate (zafirlukast), Singulair (montelukast)

Non-preferred Drugs
None

B. The Committee unanimously recommended the standard clinical questions be used as the basis for approving use of a non-preferred drug, should the Commissioner's final decision include a non-preferred drug.

Approved as Recommended
Proposal: Identification of preferred drugs in the category of Anti-Virals

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
acyclovir, famciclovir, Valtrex (valacyclovir)

Non-preferred Drugs
Famvir (famciclovir), Zovirax (acyclovir)

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 Anti-Fungals

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
ciclopirox, Grifulvin V tablet (griseofulvin), Gris-PEG (griseofulvin), griseofulvin suspension, terbinafine

Non-preferred Drugs
Grifulvin V suspension (griseofulvin), itraconazole, Lamisil (terbinafine), Penlac (ciclopirox), Sporanox (itraconazole)

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 Phosphate Binders/Regulators

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
Fosrenol (lanthanum), Phoslo (calcium acetate), Renagel (sevelamer HCL)

Non-preferred Drugs
Renvela (sevelamer carbonate)

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 Pegylated Interferons

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
PEG-Intron (peginterferon alfa-2b), Pegasys (peginterferon alfa-2a)

Non-preferred Drugs
None

B. The Committee unanimously recommended the standard clinical questions be used as the basis for approving use of a non-preferred drug, should the Commissioner's final decision include a non-preferred drug.

Approved as Recommended
Proposal: Identification of preferred drugs in the category of Immunomodulators - Topical

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
Elidel (pimecrolimus), Protopic (tacrolimus)

Non-preferred Drugs
None

B. The Committee unanimously recommended the standard clinical questions be used as a basis for approving use of a non-preferred drug, should the Commissioner's final decision include a non-preferred drug.

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 (etanercept), Humira (adalimumab)

Non-preferred Drugs
Cimzia (certolizumab pegol), Kineret (anakinra)

B. The Committee unanimously recommended the standard clinical questions be used in the prior authorization review process.

Approved as Recommended

G. Additional Discussion:

Dr. Rogler provided an overview of the New York Medicaid Clinical Drug Review Program (CDRP).

Kevin Huang-Cruz announced his resignation from the Committee to pursue other opportunities. The Committee thanked him for his service.

The meeting adjourned at 3:15 PM.

Meeting Summary Posted 10/16/08

H. Final Determinations

The Commissioner has determined that the Medicaid program will require prior authorization under the Preferred Drug Program (PDP) for non-preferred drugs, as listed above, in the following classes: Multiple Sclerosis Agents, DPP-4 Inhibitors, Inhaled Short Acting Beta2 Adrenergic Agents, Inhaled Long Acting Beta2 Adrenergic Agents, Inhaled Anticholinergics, Inhaled Corticosteroids, Leukotriene Modifiers, Anti-Virals, Anti-Fungals, Phosphate Binders/Regulators, Pegylated Interferons, Topical Immunomodulators and Injectable Immunomodulators.

Preferred Drugs will not require prior authorization

The impact of this final determination is as follows:

  1. State Public Health Population:
    • Minimal effect on Medicaid enrollees, as a large majority of enrollees currently utilize preferred products.
    • Non-preferred products remain available when prior authorized.
  2. Program Providers:
    • No impact on prescribers or pharmacies when utilizing preferred products. Prescribers, or their agents, will need to initiate the prior authorization process when ordering non-preferred products. Pharmacies will need to complete the prior authorization process for non-preferred products.
  3. State Health Program:
    • Annual gross savings associated with these therapeutic classes under the PDP are estimated at $43.2 M. The savings are achieved through changes in utilization to equally effective and less expensive drugs through the receipt of supplemental rebates from pharmaceutical manufacturers.

Final Determinations Posted 12/19/2008