Inflammatory Disorders: Drug Therapy Advancements in Specialty Pharmacy Michael McCall, Pharm.D. January 26, 2019

Transcription

1 Inflammatory Disorders: Drug Therapy Advancements in Specialty Pharmacy Michael McCall, Pharm.D. January 26, 2019

2 Today s Speaker Michael McCall, Pharm.D. PGY1 Pharmacy Resident Duquesne University AllianceRx Walgreens Prime

3 Disclosures No disclosure to report

4 Learning Objectives Upon completion of this activity, participants should be able to: Explain the inflammatory pathway involved in the pathogenesis of rheumatoid arthritis, psoriasis, and inflammatory bowel disease Review the current treatment options for the management of patients with rheumatoid arthritis, psoriasis, and inflammatory bowel disease Describe the advancements in drug therapy and compare their use in treatment to recommend an appropriate regimen based on a patient case Evaluate the role of specialty pharmacies in the management of patients with rheumatoid arthritis, psoriasis, and inflammatory bowel disease and their impact on patient outcomes

5 Rheumatoid Arthritis

6 Pathogenesis Rheumatoid Arthritis 4,6,7 Repeated activation of immune system Auto-immune inflammatory cascade T and B cells, plasma cells, macrophages, dendritic cells,synoviocytes Recognition of self proteins as foreign Auto-antibody production immune complexes Synovial joint inflammation Multiple joints affected Small joints progressing to larger joints Erosion of cartilage and bone Cytokines Osteoclast stimulation

7 Current Drug Therapy Rheumatoid Arthritis 9,10 First line Conventional disease modifying anti-rheumatic drugs (cdmard) Methotrexate (MTX), leflunomide, hydroxychloroquine, sulfasalazine Second line TNFα-inhibitor alone or in combination with MTX Adalimumab, certolizumab pegol, etanercept, golimumab, infliximab Failure on TNFα-inhibitor IL-6 inhibitor or JAK inhibitor Guidelines prefer IL-6 inhibitors Other drug therapies Abatacept, rituximab Anakinra Immunosuppressants

8 IL-6 inhibitors Rheumatoid Arthritis Tocilizumab (Actemra ) Dosing information 162 mg subcutaneously (SC) every other week; may increase to weekly 4 mg/kg intravenously (IV) every 4 weeks; may increase to 8 mg/kg every 4 weeks Safety Gastrointestinal perforations Development of multiple sclerosis Serious infections 3.8% of patients (SUMMACTA) Efficacy ACR20 (%) Tocilizumab ± MTX > MTX in naïve and experienced patients Tocilizumab effective treatment in patents with an inadequate response to TNFα-inhibitors Tocilizumab > adalimumab in patients intolerant to MTX

9 IL-6 inhibitors Rheumatoid Arthritis Sarilumab (Kevzara ) Dosing Information 200 mg SC once every two weeks. May decrease to 150 mg SC every two weeks Safety Gastrointestinal perforations Serious infections 2.6 to 4% of patients (MOBILITY) Efficacy ACR20 (%) Sarilumab > MTX monotherapy when added as combination Sarilumab + DMARD effective in patients with an inadequate response to TNFα-inhibitors Sarilumab > adalimumab in patients with an inadequate response to MTX

10 JAK inhibitors Rheumatoid Arthritis Tofacitinib (Xeljanz ) Dosing information 5 mg PO twice daily or 11 mg PO once daily (XR) Safety Malignancies Serious infections 2.5% of patients (ORAL START) Comparable discontinuation rates due to adverse events Efficacy ACR20 (%) Tofacitinib effective in patients with an inadequate response to non-biologic or biologic Tofacitinib > MTX in naïve patients Tofacitinib + MTX non-inferior to adalimumab + MTX

11 JAK inhibitors Rheumatoid Arthritis 24,25 Baricitinib (Olumiant ) Dosing information 2 mg PO once daily Safety Malignancies Serious infections 2% of patients (RA-BEAM) Thrombosis DVT and PE Efficacy ACR20 (%) Baricitinib + MTX > MTX in patients with an inadequate response to MTX or other cdmard Baricitinib > adalimumab in patients with an inadequate response to MTX or other cdmard

12 Case 1 Rheumatoid Arthritis BT is a 57 year-old female with a 15 year history of rheumatoid arthritis. Her previous treatments include methotrexate (MTX), adalimumab, and abatacept. She is currently being treated with certolizumab and still experiencing moderate RA symptoms including pain, joint swelling, and morning stiffness. BT s rheumatologists would like to switch her to another medication to better control her disease activity. What is an appropriate treatment option? A. Golimumab B. Anakinra C. Tocilizumab D. Tofacitinib

13 Psoriasis

14 Epidemiology - Psoriasis 26 Affects approximately 7.5 millions Americans Men and women equally Develops between ages 15 and 35 Beyond a cosmetic concern Mental health - twice as likely to become depressed Decreased work productivity 60% of patients missed work due to condition Cardiovascular disease 58% more likely to have an event Development of psoriatic arthritis Estimated 10 to 30% of patients Usually develops 10 years after psoriasis

15 Pathogenesis - Psoriasis 27 Immune stimulation in the epidermal layers of the skin Microbial invasion and cytokine infiltration Proliferation and thickening of keratinocytes Inflammation of the skin Causes raised, red patches that can be itchy and painful Commonly appears on elbows, knees, or scalp Five types of psoriasis Plaque psoriasis Guttate psoriasis Inverse psoriasis Pustular psoriasis Erythrodermic psoriasis

16 Current Drug Therapy Psoriasis 28 Topicals Corticosteroids, vitamin D analogues, retinoids Targeted phototherapy Excimer laser Phototherapy UVB PUVA (psoralen + UVA) Systemic agents Retinoids, immunosuppressants Biologics TNFα-inhibitors Adalimumab, etanercept, certolizumab pegol, infliximab Interleukin inhibitors

17 IL-23/12 inhibitors - Psoriasis 46,47 Ustekinumab (Stelara ) Dosing information Induction dose: 45 mg or 90 mg SC at weeks 0 and 4 Maintenance dose: 45 mg or 90 mg SC every 12 weeks thereafter, starting at week 16 Safety Reversible Posterior Leukoencephalopathy Syndrome Non-infectious pneumonia Efficacy PASI 75 (%) Ustekinumab > placebo at week 12 and 40 PASI 75 response Ustekinumab > etanercept at week 12 PASI 75 response

18 IL-17 inhibitors - Psoriasis Secukinumab (Cosentyx ) Dosing information Induction: 300 mg SC at weeks 0, 1, 2, 3, 4 Maintenance: 300 mg SC every 4 weeks Safety Infections oral candidiasis Exacerbation of inflammatory bowel disease Efficacy Secukinumab > etanercept in week 12 PASI 75 response Secukinumab > ustekinumab in week 16 PASI 90 response Results maintained at 1 year PASI 90 76%

19 IL-17 inhibitors - Psoriasis Ixekizumab (Taltz ) Dosing information Induction: 160 mg SC at week 0, followed by 80 mg at weeks 2, 4, 6, 8, 10 and 12 Maintenance: 80 mg SC every 4 weeks Safety Infections oral candidiasis Exacerbation of inflammatory bowel disease Efficacy Ixekizumab > placebo and etanercept in week 12 PASI 75 response Maintenance of PASI 75 and PASI 90 up to 60 weeks

20 IL-17 inhibitors - Psoriasis 37,38 Brodalumab (Siliq ) Dosing information Induction: 210 mg SC at weeks 0, 1, and 2 Maintenance: 210 mg SC every 2 weeks Safety Suicidal behaviors and ideation REMS Risk of flares following discontinuation Efficacy Brodalumab > placebo in week 12 PASI 75 response Brodalumab > ustekinumab in week 12 PASI 100 response

21 IL-23 inhibitors Psoriasis Guselkumab (Tremfya ) Dosing information Induction: 100 mg SC at weeks 0 and 4 Maintenance: 100 mg SC every 8 weeks Safety Adverse events comparable to adalimumab and ustekinumab Efficacy Guselkumab > adalimumab in week 16 and 24 PASI 90 response Results maintained for up to two years PASI 90 82% Guselkumab > ustekinumab in week 52 PASI 90 response Switch to guselkumab or remain on ustekinumab

22 IL-23 inhibitors Psoriasis 44,45 Tildrakizumab-asmn (Ilumya ) Dosing information Inductions: 100 mg SC at weeks 0 and 4 Maintenance: 100 mg SC every 12 weeks Safety Angioedema and urticarial Efficacy Tildrakizumab > etanercept in week 12 and 28 PASI 75 response Long-term studies showing sustained results into 2 years 80% PASI 75

23 Case 2 Psoriasis AH is a 34 year-old female with a 10 year history of plaque psoriasis. Her condition is extensive, effecting areas of her face, scalp, and palms. She has tried multiple topical treatments and suffers from depression and anxiety due to disease persistence. Other past treatments include etanercept, adalimumab, and ustekinumab. AH s dermatologist would like to switch her to another medication to better control her condition. What is an appropriate treatment option? A. Certolizumab B. Brodalumab C. Sarilumab D. Tildrakizumab E. Secukinumab

24 Case 2 Psoriasis (cont.) A few days later you receive the following prescription for AH Secukinumab (Cosentyx) 150 mg/ml pen device QTY: 1 box (2 pens) SIG: Inject 300 mg (2 pens) subcutaneously every 4 weeks What clinical intervention should be made to the prescriber?

25 Inflammatory Bowel Disease

26 Epidemiology Inflammatory Bowel Disease 48,49 Affects over 1.6 million adults in the United States Ulcerative colitis 900,000 More common in males Typically diagnosed in mid-30s Crohn s disease 780,000 Males and females equally Develops between 15 to 35 years old Disease burdens Over 100,000 hospitalizations each year 119,000 cases of disability each year Surgery CD 70% of patients with a 30% recurrence rate UC 33% of patients

27 Pathogenesis 49,50 Inappropriate immune response in GI tract Impaired epithelial barrier function Infiltration of gut microbes and foreign invaders Triggers immune cell and cytokine accumulation Inflammation of the intestinal lining Failure of regulatory T cells to control immune response Chronic inflammatory state

28 Current Drug Therapy Crohn s Disease 51 Mild Induction Budesonide ± thiopurine Steroid taper ± thiopurine Maintenance Observation Budesonide Immunosuppressive therapy Moderate to severe Induction Steroids + thiopurine TNFα-inhibitors ± thiopurine Maintenance Thiopurine TNFα-inhibitors ± thiopurine

29 Current Drug Therapy Ulcerative Colitis 52 Mild to moderate Induction Oral and/or rectal 5-ASA Oral budesonide or prednisone and/or rectal steroids Maintenance Oral and/or rectal 5-ASA Taper steroids Severe Induction Oral steroid + thiopurine TNFα-inhibitors ± thiopurine Vedolizumab Maintenance Thiopurine + steroid taper TNFα-inhibitors ± thiopurine Vedolizumab

30 IL-23/12 Crohn s Disease 53,54 Ustekinumab (Stelara ) Dosing information Induction: weight based IV infusion at week 0 Maintenance: 90 mg SC every 8 weeks, starting 8 weeks after loading dose Safety RPLS and non-infectious pneumonia Serious infections 0.5 to 2.8% (induction) and 2.3 to 5.3% (maintenance) Efficacy Ustekinumab > placebo in induction and response rates at 6 weeks UNITI-1 non-responsive to TNFα-inhibitors UNITI-2 non-responsive to conventional therapies Ustekinumab > placebo in maintenance of remission at 44 weeks

31 JAK Ulcerative Colitis 55 Tofacitinib (Xeljanz ) Dosing information 10 mg PO twice daily for at least 8 weeks, then 5 or 10 mg PO twice daily Safety Malignancies Serious infections 0.5 to 1.3% of patients Efficacy Tofacitinib > placebo in induction and response rates at 8 weeks Tofacitinib > placebo in maintenance of remission at 12 months Initial remission in OCTACVE 1 or 2 (induction) 84.4% maintenance after 12 months

32 Pharmacist Management

33 Treatment Considerations Goals of therapy Achievement of remission and minimization of adverse events Maintenance and prevention of flares Drug selection Treatment history Route of administration Monotherapy or combination Potential serious side effects Increased risk of infections and/or malignancies Hepatitis B reactivation Serious allergic reactions

34 Specialty Pharmacy 56 Coordination of Care Aims to improve patient outcomes and decrease healthcare costs Meet the needs of patients, providers, payers, manufacturers Providing optimal patient care services Proactive outreaches for refill management and delivery Adherence programs Disease state and drug monitoring, education, and counseling Benefits investigations and financial assistance Provider communication

35 Specialty Pharmacy Patient management Inflammatory Conditions Prior to starting therapy Initial TB and Hepatitis B testing Counseling on the risk of infection and warning signs Injection counseling and storage requirements Prospective dose reviews During therapy Depression screening Management of flares Side effect counseling and management Drug therapy or dose changes

36 Specialty Pharmacy Patient Impact Medication adherence Outreach programs, side effect management, proactive refills Therapy continuation Refill persistence, lower rates of discontinuation QOL measures Disease therapy management program improved physical functioning Medical costs and utilizations Financial assistance, decreased medical costs, lower ED risk Medication access Limited distribution drugs

37 Conclusion Rheumatoid arthritis, psoriasis, and inflammatory bowel disease are immunemediated inflammatory conditions Complications are common for patients, having a great impact on their quality of life New drug therapies target specific cytokines and signaling molecules Superiority over current treatments Outdated guidelines do not address place in therapy Reliance on standard practice and insurance regulations Complicated dosing regimens, proper administration, and side effect profile Specialty pharmacists play a key role in patient management Adherence barriers and medication persistence Management of flares Cost savings

38 THANK YOU!

39 QUESTIONS?

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42 References 34. DailyMed - TALTZ- ixekizumab injection, solution. U.S. National Library of Medicine. Accessed November Gordon KB, Blauvelt A, Papp KA, et al. Phase 3 trials of ixekizumab in moderate-to-severe plaque psoriasis. N Engl J Med.2016;375: Griffiths CE, Reich K, Lebwolh M, et al. Comparison of ixekizumab with etanercept or placebo in moderate-to-severe psoriasis (UNCOVER-2 and UNCOVER-3): results from two phase 3 randomised trials. Lancet. 2015;386: DailyMed - SILIQ- brodalumab injection. U.S. National Library of Medicine. Accessed November Lebwohl M, Strober B, Menter A, et al. Phase 3 Studies Comparing Brodalumab with Ustekinumab in Psoriasis. N Engl J Med. 2015;373(14): Kopf M. Psoriasis and beyond: targeting the IL-17 pathway [video]. Nature Reviews Drug Discovery. Accessed November 20, DailyMed - TREMFYA- guselkumab injection. U.S. National Library of Medicine. Accessed November Griffiths CEM, Papp KA, Kimball AB, et al. Long-term efficacy of guselkumab for the treatment of moderate-to-severe psoriasis: results from the phase 3 VOYAGE 1 trial through two years. J Drugs Dermatol. 2018;17(8): Langley RG, Tsai TF, Flavin S, et al. Efficacy and safety of guselkumab in patients with psoriasis who have an inadequate response to ustekinumab: results of the randomized, double-blind, phase III NAVIGATE trial. Br J Dermatol. 2018;178(1): Reich K, Armstrong AW, Foley P et al. Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the treatment of patients with moderate to severe psoriasis with randomized withdrawal and retreatment: Results from the phase III, double-blind, placebo- and active comparatorcontrolled VOYAGE 2 trial. J Am Acad Dermatol. 2017;76(3): DailyMed - ILUMYA- tildrakizumab injection. U.S. National Library of Medicine. Accessed November Reich K, Papp KA, Blauvelt, et al. Tildrakizumab versus placebo or etanercept for chronic plaque psoriasis (resurface 1 and resurface 2): results from two randomised controlled, phase 3 trials. Lancet. 2017;390: DailyMed - STELARA- ustekinumab injection. U.S. National Library of Medicine. Accessed November Papp KA, Langley RG, Lebwohl M, et al. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 2). Lancet. 2008;371(9625): Bhat S, Khamo N, Abdou S, et al. The Pharmacist's Role in Biologic Management for IBD in a Health System Integrated Practice Model. Am J Pharm Benefits. 2015;7(5):

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