09-J2000-19 Original Effective Date: 09/15/14 Reviewed: 09/12/18 Revised: 10/15/18 Subject: Apremilast (Otezla ) Tablet THIS MEDICAL COVERAGE GUIDELINE IS NOT AN AUTHORIZATION, CERTIFICATION, EXPLANATION OF BENEFITS, OR A GUARANTEE OF PAYMENT, NOR DOES IT SUBSTITUTE FOR OR CONSTITUTE MEDICAL ADVICE. ALL MEDICAL DECISIONS ARE SOLELY THE RESPONSIBILITY OF THE PATIENT AND PHYSICIAN. BENEFITS ARE DETERMINED BY THE GROUP CONTRACT, MEMBER BENEFIT BOOKLET, AND/OR INDIVIDUAL SUBSCRIBER CERTIFICATE IN EFFECT AT THE TIME SERVICES WERE RENDERED. THIS MEDICAL COVERAGE GUIDELINE APPLIES TO ALL LINES OF BUSINESS UNLESS OTHERWISE NOTED IN THE PROGRAM EXCEPTIONS SECTION. Dosage/ Administration Position Statement Billing/Coding Reimbursement Program Exceptions Definitions Related Guidelines Other References Updates DESCRIPTION: Apremilast (Otezla) was approved by the US Food and Drug Administration (FDA) for the treatment of adults with active psoriatic arthritis (PsA) in March 2014 and then moderate-to-severe plaque psoriasis in September 2014. Apremilast, as sponsored by the innovator drug company, also was granted orphan drug designation by the FDA for the treatment of Behçet s disease (2013) and treatment of pediatric patients with ulcerative colitis (2018). Apremilast exerts its therapeutic activity through inhibition of phosphodiesterase-4 (PDE-4). PDE-4 inhibition promotes intracellular accumulation of cyclic adenosine monophosphate; this accumulation results in a downregulation of inflammatory responses and ultimately reduces inflammation. Psoriasis is a chronic, inflammatory disease that affects approximately 3% of the adult US population. Approximately 80% of patients with psoriasis have limited disease, and, for the majority of these patients, topical treatments are safe, effective, and convenient. However, some patients require systemic treatment. Without appropriate treatment, patients may experience substantial disease burden and decreased quality of life. The American Academy of Dermatology (AAD) guidelines state that methotrexate is a logical first choice of systemic agent, because it is the most cost-effective systemic psoriasis agent with the longest safety follow-up data. Cyclosporine is cited as particularly useful in the treatment of significant flares of psoriasis unresponsive to other therapies. Intermittent, short-term therapy (12 to 16 weeks) is the most frequently recommended regimen, with treatment withdrawn once significant improvement is achieved. When relapse occurs, cyclosporine therapy is reinstituted at the previously established effective dose, or maintenance therapy for up to 1 year can be used. Acitretin
is also mentioned as an important oral option, despite it being normally less effective than other traditional systemic agents, due to its lack of immunosuppression and value in patients with known infection, active malignancy, or HIV. The use of biologic agents (TNF inhibitors and ustekinumab) is discussed as very effective treatment that can be used for patients with extensive disease. Newer biologic agents and apremilast are not yet addressed in the AAD guidelines. FDA-approval for PsA was based on three similarly designed clinical trials, PALACE-1, -2, and -3 (i.e., PsA- 1, PsA-2, and PsA-3). All three trials were multi-center, randomized, double-blind, placebo-controlled trials and enrolled a total of 1,493 subjects. Subjects were enrolled if they were diagnosed with active PsA despite previous or current treatment with a disease modifying anti-rheumatic drug (DMARD). Of note, previous treatment with a biologic, including anti-tumor necrosis factor (TNF) agents was allowed and up to 10% of subjects could be previous anti-tnf failures. The primary efficacy endpoint was the proportion of subjects achieving a 20% reduction in the American College of Rheumatology (ACR) response criteria for rheumatoid arthritis, modified for psoriatic arthritis (i.e., ACR20) at 16 weeks. Apremilast treatment resulted in significantly more subjects achieving an ACR20 response at week 16 (38%, 32% and 41% in PsA-1, -2, and -3 respectively) when compared to placebo (19%, 19%, 18%). Additionally, the number of tender and swollen joints, pain assessment and Health Assessment Questionnaire Disability Index were also improved at week 16. FDA-approval for plaque psoriasis was based on two multicenter, randomized, double-blind, placebocontrolled trials (PSOR-1 and PSOR-2) in which 1,257 subjects 18 years of age and older with moderate to severe plaque psoriasis were enrolled. Approximately 30% of subjects had received prior phototherapy and 54% had received prior conventional systemic and/or biologic therapy for the treatment of psoriasis. The primary efficacy endpoint was the proportion of subjects achieving a Psoriasis Area and Severity Index (PASI)-75 response. Apremilast treatment resulted in significantly more subjects achieving a PASI-75 response at week 16 (33.1% and 28.8% in PSOR-1 and PSOR-2, respectively) vs. placebo (5.3% and 5.8%). Also, more patients on apremilast had a Static Physician Global Assessment (spga) of clear or almost clear (21.7% and 20.4% vs. 3.9% and 4.4%). While methotrexate must be avoided in women who are pregnant or trying to become pregnant, cyclosporine and anti-tnf biologics are considered to be low-risk options during pregnancy if systemic therapy cannot be avoided. While not a first-line agent for psoriasis, sulfasalazine has adequate data supporting safe use (pregnancy Category B), and is consider a preferred DMARD if given with folic acid when systemic treatment is clinically necessary. POSITION STATEMENT: Comparative Effectiveness The Food and Drug Administration has deemed the drug(s) or biological product(s) in this coverage policy to be appropriate for self-administration or administration by a caregiver (i.e., not a healthcare professional). Therefore, coverage (i.e., administration) in a provider-administered setting such as an outpatient hospital, ambulatory surgical suite, physician office, or emergency facility is not considered medically necessary.
Initiation of apremilast (Otezla) meets the definition of medical necessity when ALL of the following criteria are met: 1. Apremilast will be used for the treatment of an indication listed in Table 1, and ALL indication-specific dose criteria are met 2. Apremilast is NOT used in combination with ANY of the following: a. abatacept (Orencia) b. adalimumab (Humira) c. anakinra (Kineret) d. baricitinib (Olumiant) e. brodalumab (Siliq) f. certolizumab (Cimzia) g. etanercept (Enbrel) h. golimumab (Simponi, Simponi Aria) i. guselkumab (Tremfya) j. infliximab products (Remicade, Inflectra, Renflexis) k. ixekizumab (Taltz) l. sarilumab (Kevzara) m. secukinumab (Cosentyx) n. tildrakizumab-asmn (Ilumya) o. tocilizumab (Actemra) p. tofacitinib (Xeljanz, Xeljanz XR) q. ustekinumab (Stelara) r. vedolizumab (Entyvio) 3. Dosage of apremilast does not exceed 30 mg twice daily Table 1 Indications and Specific Criteria Indication Criteria Psoriatic arthritis (PsA) [including both axial and nonaxial (peripheral) PsA] When ALL of the following are met ( 1, 2, and 3 ): 1. Member s disease is active (i.e., persistent joint inflammation) 2. EITHER of the following based on the dominate disease type ( a or b ): a. Axial PsA: Member has had an inadequate response to, or has a contraindication to at least TWO different NSAID therapies taken continuously for at least 4 weeks each* (e.g., celecoxib,
diclofenac, ibuprofen, meloxicam naproxen) b. Peripheral PsA: Member has had an inadequate response to, or has a contraindication to at least ONE NSAID therapy taken continuously for at least 4 weeks* (e.g., celecoxib, diclofenac, ibuprofen, meloxicam, naproxen) (the specific contraindication must be provided) AND Member has had an inadequate response to, or has a contraindication to methotrexate at the maximally tolerated dosage (e.g., methotrexate titrated to 25 mg weekly), or, if methotrexate is contraindicated, to another csdmard* (e.g., cyclosporine, leflunomide, sulfasalazine) 3. Member is 18 years of age or older Plaque psoriasis When ALL of the following are met ( 1, 2, and 3 ): Orphan Indications 1. Member s disease is moderate to severe as evidenced by EITHER of the following before or after systemic drug therapy ( a or b ): a. Psoriasis covers 10% or more of member s body surface area (BSA) b. Psoriasis covers less than 10% of member s BSA but affects crucial body areas necessary for daily living activities (i.e., face, palms of hands, soles of feet, or genitals) 2. EITHER of the following* ( a or b ): a. Member has had an inadequate response to at least 3 months of continuous treatment with maximally tolerated methotrexate (e.g., titrated to a dosage of 25 mg per week), oral cyclosporine (at a dosage of at least 4 mg/kg per day), or acitretin (at a dosage of at least 25 mg per day), OR the member has contraindications and/or intolerances to all three drugs [the specific contraindication(s) and/or intolerance(s) must be provided] b. The member has had an inadequate response to a 3-month or greater trial or has a contraindication to phototherapy (e.g., PUVA, UVB) - the specific contraindication must be provided 3. Member is 18 years of age or older Behçet s syndrome When BOTH of the following are met ( 1 and 2 ): 1. Member has recurrent oral mucocutaneous ulcerations 2. The member has had an inadequate response, intolerable adverse effects, or a contraindication to treatment with the following [the specific adverse effects(s) and/or contraindication(s) must be provided]: a. Azathioprine
b. Colchicine c. Systemic corticosteroid (e.g., prednisone) Pediatric ulcerative colitis (UC) When ALL of the following are met ( 1, 2, 3, and 4 ): Approval duration: 6 months 1. Member is less than 18 years of age 2. Member s disease is moderately to severely active 3. EITHER of the following* ( a or b ): a. Member has had an inadequate response to, or has a contraindication to systemic corticosteroid therapy (the specific contraindication must be provided) b. Member is dependent on systemic corticosteroids [i.e., unable to successfully taper corticosteroids to less than 10 mg of prednisone (or equivalent) within 3 months of initiation without return of symptoms] 4. Member has had an inadequate response to ANY, or has a contraindication to ALL of the following* (the specific contraindications must be provided): a. Oral aminosalicylates (i.e., sulfasalazine, olsalazine, mesalamine, or balsalazide) b. Topical aminosalicylates (e.g., enema or suppository) c. Thiopurine therapy (e.g., azathioprine or 6-mercaptopurine [6- MP]) *NOTE: if the member has had an inadequate response to previous biologic therapy that is FDAapproved for the requested indication listed in Table 1, the member is not required to have had an inadequate response to non-biologic prerequisite therapy (e.g., for psoriasis, if member has previously had an inadequate response to etanercept, but does not have a history of inadequate response to methotrexate, they do not have to try methotrexate to meet medical necessity criteria). Continuation of apremilast (Otezla) meets the definition of medical necessity when ALL of the following criteria are met ( 1 to 4 ): 1. An authorization or reauthorization for apremilast has been previously approved by Florida Blue or another health plan in the past 2 years for the treatment of a condition listed in Table 1, OR the member has previously met ALL indication-specific initiation criteria 2. The member has demonstrated a beneficial clinical response to apremilast therapy 3. The dosage of apremilast does not exceed 30 mg twice daily. 4. Apremilast is NOT used in combination with ANY of the following: a. abatacept (Orencia) b. adalimumab (Humira)
c. anakinra (Kineret) d. baricitinib (Olumiant) e. brodalumab (Siliq) f. certolizumab (Cimzia) g. etanercept (Enbrel) h. golimumab (Simponi, Simponi Aria) i. guselkumab (Tremfya) j. infliximab products (Remicade, Inflectra, Renflexis) k. ixekizumab (Taltz) l. sarilumab (Kevzara) m. secukinumab (Cosentyx) n. tildrakizumab-asmn (Ilumya) o. tocilizumab (Actemra) p. tofacitinib (Xeljanz, Xeljanz XR) q. ustekinumab (Stelara) r. vedolizumab (Entyvio) Approval duration: 1 year DOSAGE/ADMINISTRATION: THIS INFORMATION IS PROVIDED FOR INFORMATIONAL PURPOSES ONLY AND SHOULD NOT BE USED AS A SOURCE FOR MAKING PRESCRIBING OR OTHER MEDICAL DETERMINATIONS. PROVIDERS SHOULD REFER TO THE MANUFACTURER S FULL PRESCRIBING INFORMATION FOR DOSAGE GUIDELINES AND OTHER INFORMATION RELATED TO THIS MEDICATION BEFORE MAKING ANY CLINICAL DECISIONS REGARDING ITS USAGE. FDA-approved: Apremilast is indicated for the treatment of adults with active psoriatic arthritis and patients with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy. To reduce the risk of gastrointestinal symptoms, the following titration schedule is recommended: Day 1: 10 mg in the morning Day 2: 10 mg in morning and 10 mg in evening Day 3: 10 mg in morning and 20 mg in evening Day 4: 20 mg in morning and 20 mg in evening Day 5: 20 mg in morning and 30 mg in evening Day 6: 30 mg twice daily
Dose Adjustments: Reduce the dose to 30 mg once daily for persons with severe renal impairment (i.e., creatinine clearance less than 30 ml/min). For initial dose titration, titrate using only the morning schedule and skip evening doses. No dose adjustment is necessary in patients with hepatic impairment. Product Availability: apremilast is supplied as 10-, 20-, and 30-mg tablets. PRECAUTIONS: Boxed Warning None Contraindication Known hypersensitivity to apremilast or any excipients in the formulation Precautions/Warnings Diarrhea, Nausea, and Vomiting: There have been postmarketing reports of severe diarrhea, nausea, and vomiting associated with the use of apremilast. Most events occurred within the first few weeks of treatment. Monitor patients who are more susceptible to complications of diarrhea or vomiting. Patients who reduced dosage or discontinued treatment generally improved quickly. Consider dose reduction or suspension if patients develop severe diarrhea, nausea, or vomiting. Depression: Advise patients, their caregivers, and families to be alert for the emergence or worsening of depression, suicidal thoughts or other mood changes and if such changes occur to contact their healthcare provider. Carefully weigh risks and benefits of treatment with apremilast in persons with a history of depression and/or suicidal thoughts or behavior. Weight Decrease: Monitor weight regularly. If unexplained or clinically significant weight loss occurs, evaluate weight loss and consider discontinuation of apremilast. Drug Interactions: Use with strong cytochrome P450 enzyme inducers (e.g. rifampin, phenobarbital, carbamazepine, phenytoin) is not recommended because loss of efficacy may occur. BILLING/CODING INFORMATION: The following codes may be used to describe: HCPCS Coding J8499 Prescription drug, oral, non-chemotherapeutic, NOS ICD-10 Diagnosis Codes That Support Medical Necessity K51.00 K51.919 Ulcerative colitis L40.0 Psoriasis vulgaris
L40.50 Arthropathic psoriasis, unspecified L40.51 Distal interphalangeal psoriatic arthropathy L40.52 Psoriatic arthritis mutilans L40.53 Psoriatic spondylitis L40.59 Other psoriatic arthropathy M35.2 Behçet's disease REIMBURSEMENT INFORMATION: Refer to section entitled POSITION STATEMENT. PROGRAM EXCEPTIONS: Federal Employee Program (FEP): Follow FEP guidelines. State Account Organization (SAO): Follow SAO guidelines. Medicare Advantage Products: No National Coverage Determination (NCD) and/or Local Coverage Determination (LCD) were found at the time of the last guideline review date. Medicare Part D: Florida Blue has delegated to Prime Therapeutics authority to make coverage determinations for the Medicare Part D services referenced in this guideline. DEFINITIONS: Axial PsA (a.k.a., psoriatic spondylitis): a subset of psoriatic arthritis that affects the spine (i.e., spondylitis) and/or spinal joints (e.g., the sacroiliac joint between the sacrum and ilium of pelvis). Axial PsA shares similar clinical findings to patients with ankylosing spondylitis (AS); however, patients with axial PsA are often less symptomatic, have asymmetric disease, and tend to have less severe disease. In addition, the psoriatic plaques or nail changes present in patients with axial PsA are absent in patients with AS. About 5% of PsA patients have exclusively axial involvement, and 20 to 50% have both spinal and peripheral involvement, with peripheral joint involvement being the predominant pattern. DMARDs: An acronym for disease-modifying antirheumatic drugs. These are drugs that modify the rheumatic disease processes, and slow or inhibit structural damage to cartilage and bone. These drugs are unlike symptomatic treatments such as NSAIDs that do not alter disease progression. DMARDs can be further subcategorized. With the release of biologic agents (e.g., anti-tnf drugs), DMARDs were divided into either: (1) conventional, traditional, synthetic, or non-biological DMARDs; or as (2)
biological DMARDs. However, with the release of newer targeted non-biologic drugs and biosimilars, DMARDs are now best categorized as: (1) conventional synthetic DMARDs (csdmard) (e.g., MTX, sulfasalazine), (2) targeted synthetic DMARDs (tsdmard) (e.g., baricitinib, tofacitinib, apremilast), and (3) biological DMARDs (bdmard), which can be either a biosimilar DMARD (bsdmard) or biological originator DMARD (bodmard). Non-axial or peripheral PsA: a subset of psoriatic arthritis that does NOT affect the spine or spinal joints [e.g. elbow, wrist, knees, hands, feet, and digits (dactylitis)]. Peripheral involvement may be polyarticular (5 or more joints affected) or oligoarticular (a.k.a., pauciarticular) (4 or fewer joints affected). Approximately 95% of patients with PsA have involvement of the peripheral joints, predominantly the polyarticular form, whereas a minority has the oligoarticular form. Plaque psoriasis: It is the most common form of psoriasis. It affects 80 to 90% of people with psoriasis. Plaque psoriasis typically appears as raised areas of inflamed skin covered with silvery white scaly skin. These areas are called plaques. Psoriasis Area Severity Index (PASI): An index used to express the severity of psoriasis. It combines the severity (erythema, induration and desquamation) and percentage of affected area. The score ranges from 0 (no psoriasis on the body) to 72 (the most severe case of psoriasis). A score of 11 or greater suggests moderate-to-severe psoriasis. A web-based calculator can be found at: http://www.pasitraining.com Psoriatic arthritis: joint inflammation that occurs in about 5% to 10% of people with psoriasis (a common skin disorder). It is a severe form of arthritis accompanied by inflammation, psoriasis of the skin or nails, and a negative test for rheumatoid factor. Enthesitis refers to inflammation of entheses, the site where ligaments or tendons insert into the bones. It is a distinctive feature of PsA and does not occur with other forms of arthritis. Common locations for enthesitis include the bottoms of the feet, the Achilles' tendons, and the places where ligaments attach to the ribs, spine, and pelvis. RELATED GUIDELINES: Abatacept (Orencia), 09-J0000-67 Adalimumab (Humira), 09-J0000-46 Brodalumab (Siliq) Injection, 09-J2000-74 Certolizumab Pegol (Cimzia), 09-J0000-77 Etanercept (Enbrel), 09-J0000-38 Golimumab (Simponi, Simponi Aria), 09-J1000-11 Guselkumab (Tremfya), 09-J2000-87
Infliximab Products [infliximab (Remicade), infliximab-dyyb (Inflectra), and infliximab-abda (Renflexis)], 09-J0000-39 Ixekizumab (Taltz), 09-J2000-62 Psoralens with Ultraviolet A (PUVA), 09-10000-16 Secukinumab (Cosentyx), 09-J2000-30 Tildrakizumab-asmn (Ilumya), 09-J3000-04 Ustekinumab (Stelara), 09-J1000-16 OTHER: Table 1: Conventional Synthetic DMARDs DMARD Generic Name Auranofin (oral gold) Azathioprine Cyclosporine Hydroxychloroquine Leflunomide Methotrexate Sulfasalazine DMARD Brand Name Ridaura Imuran Neoral, Sandimmune Plaquenil Arava Rheumatrex, Trexall Azulfidine, Azulfidine EN-Tabs REFERENCES: 1. Armstrong AW, Siegel MP, Bagel J, et al. From the Medical Board of the National Psoriasis Foundation: Treatment targets for plaque psoriasis. J Am Acad Dermatol. 2017 Feb;76(2):290-298. 2. Canadian Psoriasis Guidelines Addendum Committee. 2016 Addendum to the Canadian Guidelines for the Management of Plaque Psoriasis 2009. J Cutan Med Surg. 2016 Sep;20(5):375-431. 3. Clinical Pharmacology [database online]. Tampa, FL: Gold Standard, Inc.; 2018. Available at: www.clinicalpharmacilogy-ip.com. Accessed 8/8/17. 4. Coates LC, Kavanaugh A, Mease PJ et al. Group for Research and Assessment of Psoriasis and Psoriatic Arthritis: Treatment Recommendations for Psoriatic Arthritis 2015. Arthritis Rheumatol 2016;68:1060 71
5. Crowley J, Thaçi D, Joly P, et al. Long-term safety and tolerability of apremilast in patients with psoriasis: Pooled safety analysis for 156 weeks from 2 phase 3, randomized, controlled trials (ESTEEM 1 and 2). J Am Acad Dermatol. 2017 Aug;77(2):310-317.e1. 6. Dogra S, Jain A, Kanwar AJ. Efficacy and safety of acitretin in three fixed doses of 25, 35 and 50 mg in adult patients with severe plaque type psoriasis: a randomized, double blind, parallel group, dose ranging study. J Eur Acad Dermatol Venereol. 2013 Mar;27(3):e305-11. 7. Dogra S, Krishna V, Kanwar AJ. Efficacy and safety of systemic methotrexate in two fixed doses of 10 mg or 25 mg orally once weekly in adult patients with severe plaque-type psoriasis: a prospective, randomized, double-blind, dose-ranging study. Clin Exp Dermatol. 2012 Oct;37(7):729-34. 8. Edwards CJ, Blanco FJ, Crowley J, et al. Apremilast, an oral phosphodiesterase 4 inhibitor, in patients with psoriatic arthritis and current skin involvement: a phase III, randomised, controlled trial (PALACE 3). Ann Rheum Dis. 2016 Jun;75(6):1065-73. 9. FDA Orphan Drug Designations and Approvals [Internet]. Washington, D.C. [cited 2018 August 28]. Available from: http://www.accessdata.fda.gov/scripts/opdlisting/oopd/. 10. Gossec L, Smolen JS, Ramiro S, et al. European League Against Rheumatism (EULAR) recommendations for the management of psoriatic arthritis with pharmacological therapies: 2015 update. Ann Rheum Dis. 2016 Mar;75(3):499-510. 11. Gottlieb A, Korman NJ, Gordon KB, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 2. Psoriatic arthritis: overview and guidelines of care for treatment with an emphasis on the biologics. J Am Acad Dermatol. 2008 May;58(5):851-64. doi: 10.1016/j.jaad2008.02.040. 12. Hatemi G, Melikoglu M, Tunc R, et al. Apremilast for Behçet's syndrome--a phase 2, placebocontrolled study. N Engl J Med. 2015 Apr 16;372(16):1510-8. 13. Hsu S, Papp KA, Lebwohl MG, et al. Consensus guidelines for the management of plaque psoriasis. Arch Dermatol 2012;148(1):95-102. 14. Kavanaugh A, Mease PJ, Gomez-Reino JJ, et al. Treatment of psoriatic arthritis in a phase 3 randomized, placebo-controlled trial with apremilast, an oral phosphodiesterase 4 inhibitor. Ann Rheum Dis. Mar 4 2014. 15. Krause ML, Amin A, and Makol A. Use of DMARDs and biologics during pregnancy and lactation in rheumatoid arthritis: what the rheumatologist needs to know. Ther Adv Musculoskelet Dis. 2014 Oct; 6(5): 169 184. 16. Leccese P, Ozguler Y, Christensen R, et al. Management of skin, mucosa and joint involvement of Behçet's syndrome: A systematic review for update of the EULAR recommendations for the management of Behçet's syndrome. Semin Arthritis Rheum. 2018 May 19. 17. Menter A, Gottlieb A, Feldman SR, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 1. Overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics. J Am Acad Dermatol. 2008 May;58(5):826-50. 18. Mentor A, Korman NJ, Elmets CA, et al. Guidelines for the treatment of psoriasis and psoriatic arthritis: case-based presentations and evidence-based conclusions. J Am Acad Dermatol 2011;65:137-74. 19. Nast A, Gisondi P, Ormerod AD, et al. European S3-Guidelines on the systemic treatment of psoriasis vulgaris--update 2015--Short version--edf in cooperation with EADV and IPC. J Eur Acad Dermatol Venereol. 2015 Dec;29(12):2277-94. 20. Otezla (apremilast) [package insert]. Celgene Corp. Summit (NJ): June 2017. 21. Papp K, Reich K, Leonardi CL, et al. Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor, in patients with moderate to severe plaque psoriasis: Results of a phase III, randomized, controlled trial (Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis [ESTEEM] 1). J Am Acad Dermatol. 2015 Jul;73(1):37-49
22. Paul C, Cather J, Gooderham M, et al. Efficacy and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in patients with moderate-to-severe plaque psoriasis over 52 weeks: a phase III, randomized controlled trial (ESTEEM 2). Br J Dermatol. 2015 Dec;173(6):1387-99. 23. Rahimi R, Nikfar S, Rezaie A, et al. Pregnancy outcome in women with inflammatory bowel disease following exposure to 5-aminosalicylic acid drugs: a meta-analysis. Reprod. Toxicol;2008:25,271 275. 24. Rich P, Gooderham M, Bachelez H, et al. Apremilast, an oral phosphodiesterase 4 inhibitor, in patients with difficult-to-treat nail and scalp psoriasis: Results of 2 phase III randomized, controlled trials (ESTEEM 1 and ESTEEM 2). J Am Acad Dermatol. 2016 Jan;74(1):134-42. 25. Sbidian E, Chaimani A, Garcia-Doval, et al. Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis. Cochrane Database Syst Rev. 2017 Dec 22;12:CD011535. 26. Schett G, Wollenhaupt J, Papp K, et al. Oral apremilast in the treatment of active psoriatic arthritis: Results of a multicenter, randomized, double-blind, placebo-controlled study. Arthritis Rheum. 2012;64(10):3156-3167. 27. Smith CH, Jabbar-Lopez JK, Yiu ZZ, et al. British Association of Dermatologists guidelines for biologic therapy for psoriasis 2017. Br J Dermatol 2017; 177: 628-136. 28. Wells AF, Edwards CJ, Kivitz AJ, et al. Apremilast monotherapy in DMARD-naive psoriatic arthritis patients: results of the randomized, placebo-controlled PALACE 4 trial. Rheumatology (Oxford). 2018 Apr 4. COMMITTEE APPROVAL: This Medical Coverage Guideline (MCG) was approved by the Florida Blue Pharmacy Policy Committee on 09/12/18. GUIDELINE UPDATE INFORMATION: 09/15/14 New Medical Coverage Guideline. 12/15/14 Revision to guideline. 04/15/15 Revision of guideline; consisting of position statement to exclude combination therapy. 09/15/15 Review and revision of guidelines; consisting of updating description section, position statement, dosage/administration, billing/coding, related guidelines, definitions, and references. 11/01/15 Revision: ICD-9 Codes deleted. 09/15/16 Review and revision of guidelines consisting of updating description section, position statement, billing/coding, related guidelines, and references. 02/01/17 Revision to guideline consisting of removing the two preferred agent prerequisite
requirement. 10/15/17 Review and revision to guideline consisting of updating description, position statement, dosage/administration, definitions, related guidelines, and references. 07/01/18 Revision to guideline consisting of updating the position statement. 10/15/18 Review and revision to guideline consisting of updating the position statement, billing/coding, and references.