Policy Subject: Anti-TNF Agents Policy Number: SHS PBD16 Category: Rheumatology & Autoimmune Policy Type: Medical Pharmacy Department: Pharmacy Product (check all that apply): Group HMO/POS Individual HMO/POS PPO ASO s: Effective : July 12, 2006 Revision November 20, 2017 Approval : August 23, 2017 Next Review : August 2018 Clinical Approval By: Medical Directors PHP: Peter Graham, MD; SPHN: Harman Nagler, MD Pharmacy and Therapeutics Committee PHP: Peter Graham, MD; Sparrow ASO: Harman Nagler, MD Policy Statement: Physicians Health Plan, PHP Insurance & Service Company, and Sparrow PHP will cover anti-tnf agents through the Pharmacy or Medical Benefit based on approval by the Clinical Pharmacist or Medical Director using the following determination guidelines Drugs and Applicable Coding: J-code: Enbrel-J1438; Humira-J0135; Remicade-J1745; Inflectra-Q5102; Cimzia-J0718; Simponi-J1602 Renflexis - pending Clinical Determination Guidelines: Document the following with chart notes I. General Criteria & Information A. Other therapies: Failed or had significant adverse effects w 2 preferred TNF agents 1. Categories a. Rx: Enbrel, Humira, (self-injected), b. Medical: Remicade/Inflectra/Renflexis, Simponi Aria (medical infused) 2. Grandfather status: Patients currently on non-preferred TNF agents may continue therapy. B. Familial history, past or concomitant disease states 1. Cancer: Family history, past or concomitant cancer is not a contraindication for TNF therapy C. Dosage regimen & calculation 1. Titration: Start with lower dose & titrate up to response 2. Dosage regimen: a. Within the FDA approved range: Approve per disease state b. Outside the FDA approved range Infliximab & adalimumab: Draw trough drug/antibody levels & follow appendix I table Other anti-tnf drugs: Base on disease activity 3. Calculate: mg/kg dose & round to the closest vial size (< ½ vial - round, > ½ vial - round ) D. Approval 1. Initial: 6 months 2. Re-approval: 1 yr. ( or sustained in disease activity) Page 1 of 5
II. Inflammatory Joint Diseases A. Rheumatoid Arthritis (RA) 1. Diagnosis & severity: Moderate - severe 2. Other therapies: Failed or had significant adverse events w 2 chronic therapies w different MOA: a. DMARD (4 mons.): Leuflonomide/MTX, hydroxychloroquine, sulfasalazine 3. Exclude: Simponi, Cimzia 4. Dosage regimen: Suggested in combo w MTX a. Remicade/Inflectra/Renflexis (infliximab IV): 3mg/Kg IV at 0, 2, 6 wks; then 3-10 mg/kg IV/8 wks b. Enbrel (etanercept SC): 50mg/wk or 25mg SC 2x/wk. c. Humira (adalimumab SC): 40mg/2 wks; may to wkly. if monotherapy B. Psoriatic Arthritis (PA) 1. Diagnosis & severity: Active PA w > 5 swollen and > 5 tender joints 2. Other therapies: Failed or significant adverse effects 2 chronic therapies w different MOA a. Chronic DMARD (4 mons.): MTX/leflunomide, cyclosporin, sulfasalazine 3. Exclude: Simponi, Cimzia 4. Dosage regimen a. Remicade/Inflectra/Renflexis (infliximab IV): 5mg/Kg at 0, 2, 6 wks then 5mg/Kg/8 wks. b. Enbrel (etanercept SC): 50mg/wk or 25mg 2x wk. c. Humira (adalimumab SC): 40mg/2 wks (in conjunction with other DMARD s) C. Ankylosing Spondylitis (AS) 1. Diagnosis & severity: Active AS 2. Other therapies: Failed or significant adverse effects w 2 agent s w different mechanism of action (MOA): a. DMARD (4 mons.): MTX/leflunomide, sulfasalazine a. Remicade/Inflectra/Renflexis (infliximab VI): 5mg/Kg at 0, 2, 6 wks; then 5mg/Kg/6 wks b. Enbrel (etanercept SC): 50mg/wk or 25mg 2x/wk c. Humira (adalimumab SC): 40mg/2 wks (in conjunction with other DMARD s) D. Juvenile Idiopathic Arthritis (JIA) 1. Diagnosis & severity: Mod - severe active polyarticular JIA 2. Other therapies: Failed or significant adverse effects w 2 chronic therapies w different MOA a. DMARD (4 mons.): Anakinra, MTX, leflunomide a. Enbrel (etanercept SC): <31Kg - 0.8mg/Kg/wk; >31-62Kg - 0.4mg/Kg 2x/wk; >63Kg - 50mg/wk b. Humira (adalimumab SC): >30Kg - 40mg/2wks.; 15-30Kg - 20mg/2wks. Page 2 of 5
III. Inflammatory Bowel Disease A. Crohn s Disease (CD) 1. Diagnosis & severity: Mod - severe CD 2. Other therapies: Failed or significant adverse effects w 1 of each category: a. Conventional therapies (4 mons.): Mesalamine, metronidazole 3. b. DMARD (4 mons.): Thiopurines (azathioprine/6-mp), MTX 4. Exclude: Cimzia, 5. Dosage regimen a. Remicade/Inflectra/Renflexis (infliximab IV): 5mg/Kg at 0, 2, 6 wks then 5mg/Kg/8 wks b. Humira (adalimumab SC): Adults: 160 mg wk 0 (4 x 40mg/day or 2 x 40mg/day x 2 days), 80mg wk 2, then 40mg/2 wks. Children: 17 to < 40Kg - 80mg (2 x 40mg day 1),40mg day 15 then 20mg/2wk B. Ulcerative colitis (UC) 1. Diagnosis & severity: Mod-severe UC 2. Other therapies: Failed or significant adverse effects w 1 of each category: a. Conventional therapies (4 mons.): mesalamine, metronidazole 3. Chronic DMARD (4 mons.): Sulfasalazine 4. Exclude: Simponi 5. Dosage regimen a. Remicade/Inflectra/Renflexis (infliximab IV): 5mg/Kg at 0, 2, 6 wks then 5mg/Kg/8 wks b. Humira (adalimumab SC): 160 mg wk 0 (4 x 40mg/day or 2 x 40mg/day x 2 days), 80mg wk 2, then 40mg/2 wks. (adults only) IV. Dermatological Diseases A. Plaque Psoriasis (PP) 1. Diagnosis & severity: Chronic, Severe PP with > 10% BSA affected 2. Other therapies: Failed or significant adverse effects w 2 of category a, 1 of b: a. Local therapies (4 mons.): Topical (steroids, vit. D analogues, coal tar, dithranol), phototherapy, photochemotherapy, b. Systemic therapy (4 mons.): Cyclosporine, MTX a. Remicade/Inflectra/Renflexis (infliximab IV): 5mg/Kg at 0, 2, 6 wks then 5mg/Kg/6 wks b. Enbrel (etanercept SC): 50mg 2x wkly for 3 mons. then 50mg/wk. c. Humira (adalimumab SC): 80mg at wk 0, 40mg at wk 1; then 40mg/2 wks. B. Hidradenitis Suppurativa (HS) 1. Disease severity: Mod-severe chronic HS 2. Other therapies: Failed or significant adverse effects w 1 of each category a. Local therapies (4 mons.): Topical clindamycin (mild dx), intra-lesional triamcinolone b. Systemic therapies (4 mons.): Clindamycin + rifampicin (both 300mg bid po), acitretin, finasteride/spironolactone (female pts.), cyclosporine, dapsone, 3. Dosage Regimen a. Humira (adalimumab SC): 160mg (4 x 40mg day or 2x 40mg day 1 & 2), 80mg day 15, then 40mg/wk Page 3 of 5
Appendix I: Therapeutic Drug Monitoring of Anti-TNF Agents Infliximab (Remicade) Adalimumab (Humira) Antibody level Drug Level Antibody level Drug Level <3 µg/ml >3 µg/ml < 4.5µg/ml >4.5 ug/ml Low <9 Dose Switch agent Low <4 Dose Switch agent High >9 Switch agent Switch agent High >4 Switch agent Switch agent Appendix II: Monitoring & Patient Safety Drug Adverse Reactions Monitoring REMS Cimzia GI: Nausea (<11%) Not (certolizumab) Infection (38%) needed Resp: URI (18-20%) since 12/11 Enbrel (etanercept) Humira (adalimumab) Remicade (infliximab) Simponi (golimumab) CNS: HA (17-19%) Derm: 3-13% Infection (50-81%) Immunologic: antibodies (15%), +ANA (11%), Local: Injection site Rx (14-43%) Resp: Non-URI (21-54%), URI (38-65%), rhinitis (12%) CNS: HA (12%) Derm: Rash (6-12%) Immunologic: antibodies (3-16%) Infection (1.4-6.7 event/person yrs) Local: Injection site rx (12-20%) Resp: Sinusitis (11%), URI (17%) CNS: Headache (18%) GI: Abd pain (12-26%), diarrhea (12%), nausea (21%) Hepatic: LFT (50%) Immunologic: Drug antibodies (10-51%), +ANA (50%), Infection: Infection (27-36%), Resp: Cough (12%), Pharyngitis (12%), Sinusitis (14%), URI (32%) Immunologic: antibodies (4%), +ANA (4%), Infections (27-28%), Resp: URI (13-16%) Infection: Watch for signs & symptoms (S/Sx); D/C drug if serious (Black box) TB: Test prior to tx; watch for S/Sx UC or Dysplasia/Colon CA: Check intermittently CHF: Watch for S/Sx; D/C if worse HBV: Watch for S/Sx Page 4 of 5
References and Resources: 1. Sparrow Health System Infusion Center History and Physical Remicade Orders 2. Lexicomp Online, Lexi-Drugs, Hudson, Ohio: Lexi-Comp, Inc.; Remicade, Enbrel, Humira, Simponi, Cimzia, Stelara, accessed July 2017 3. Psoriasis and Psoriatic Arthritis. A Treatment Guide for the Health Insurance Industry.National Psoriasis Foundation. 2004;1-18. 4. Management of Crohn s Disease - A Practical Approach. American Family Physician.2003:68(4); 5. Spondyloarthritis: Update on Pathogenesis & Management: Juvenile Idiopathic Arthritis. Pediatric Clinics of North America.2005:52(2) 6. Hidradenitis Suppurativa: A review of cause & treatment. Current opinions in Infectious disease 2011:24;118-123 7. Meta-analysis of the efficacy and safety of adalimumab, etanercept, and infliximab for the treatment of rheumatoid arthritis. Pharmacotherapy 2010; 30(4);339-53 8. Agency for Healthcare research and Quality (AHRQ) National Guideline Clearing House accessed April 2017: a. Clinical practice guidelines for the treatment of patient s w axial spondyloarthritis & psoriatic arthritis. b. 2013 update of the 2011 American College of Rheumatology recommendations for the treatment of JIA: recommendations for medical therapy of children w systemic JIA c. 2012 update of the 2008 American College of Rheumatology recommendation for the use of diseasemodifying anti-rheumatic drugs & biologic agents in the treatment of rheumatoid arthritis d. Ulcerative Colitis. Management in adults, children & young people e. American Gastroenterological Association institute guidelines on the use of thiopurines, methotrexate and anti-tnf biological drugs for the induction and maintenance of remission in inflammatory Crohn s disease f. Psoriasis: The assessment & management of psoriasis. 9. Levels of drug & antidrug antibodies are associated w outcome interventions after loss of response to infliximab or adalimumab. Clin Gastroenterol Hepatpl 2015:13(522);522-30 10. Trough concentrations of infliximab guide dosing for patients with IBD. Gastroenterology.2015;148;1133-9 Approved By: Peter Graham, MD PHP Executive Medical Director 12/6/17 12/6/17 Harman Nagler, MD SPHN Executive Medical Director Human Resources 12/6/17 Page 5 of 5