Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Prenatal development wikipedia , lookup
Gene therapy of the human retina wikipedia , lookup
Non-specific effect of vaccines wikipedia , lookup
Hygiene hypothesis wikipedia , lookup
Focal infection theory wikipedia , lookup
Infection control wikipedia , lookup
Herpes simplex research wikipedia , lookup
Sjögren syndrome wikipedia , lookup
Pearls and Practical Considerations for Biologic Agents Scott Vogelgesang, MD Shane Madsen, PharmD, BCPS Division of Immunology, Rheumatology and Allergy University of Iowa Department of Pharmaceutical Care University of Iowa Hospitals & Clinics Disclosure • Scott Vogelgesang and Shane Madsen report no actual or potential conflicts of interest associated with this presentation. Learning Objectives • Upon successful completion of this activity, participants should be able to: • Differentiate between biologic agents • Identify potential short and long-term adverse events that may occur with biologic agents • Develop an appropriate screening and monitoring plan for various biologic agents • Discuss pertinent patient counseling points for patients who are prescribed biologic agents Outline • Introduction • Rheumatoid arthritis • Systemic Lupus Erythematosus • belimumab • tocilizumab • Screening prior to initiation • labs • medical considerations • vaccines • tofacitinib • On treatment considerations • anakinra • Pipeline • TNF antagonists • abatacept • rituximab • Psoriatic arthritis • ustekinumab • secukinumab • apremilast • Take home points Introduction • Therapy of Rheumatoid Arthritis – interesting history • Gold • Everyone “knew” RA was caused by infection • No antibiotics – experimentation with heavy metals as therapy • Gold – those with arthritis got better • Hydroxychloroquine – 1940’s antimalarial - those w/ arthritis got better • First “designer drug” – sulfasalazine • Everyone “knew” RA was an infection so use an antibiotic (sulfapyradine) • Everyone knew aspirin helped RA so use salicylate • Combined the two: sulfasalazine • Skip ahead to 1990s – Immunologists recognized that TNF and IL-1 were responsible for the inflammatory response in RA – Development of anti-TNF and anti-IL-1 drugs • Since: Understand and target pieces of the immune system… Summary RHEUMATOID ARTHRITIS Rheumatoid arthritis is a systemic inflammatory disease which manifests itself in multiple joints of the body. The inflammatory process primarily affects the lining of the joints (synovial membrane), but can also affect other organs. The pathophysiology involves antibody, B cells, T cells and cytokines. http://www.cdc.gov/arthritis/basics/rheumatoid.htm TNF Antagonists • Inhibits Tumor Necrosis Factor • Adverse Effects • Infections • Upper respiratory infections • Urinary tract infections • Reactivation of TB • Fungal infections • Reactivation of hepatitis B • Demyelinating Disease / Neuropathies • Malignancy (Lymphoma)? • Lupus-like reactions • Avoid in heart failure TNF Antagonists • Etanercept (Enbrel) • Adalimumab (Humira) • Soluble TNF receptor • Humanized TNF antibody • Subcutaneous • Subcutaneous • Short half-life • Moderate half-life • Infliximab (Remicade) • Chimeric TNF antibody • Golimumab (Simponi & Simponi Aria) • Infusion • Humanized TNF antibody • Longest half-life • Subcutaneous & infusion • Certolizumab (Cimzia) • Humanized TNF antibody • Subcutaneous • Moderate half-life • Long half-life Abatacept (Orencia) • CTLA4 Ig – Blocks T cell signaling and therefore T cell activation • Subcutaneous & infusion • Side Effects • Infusion Reactions • Infection • ? Increased cancer (lymphoma) risk Rituximab (Rituxan) • Monoclonal antibody directed against CD20 - Depletes B cells • IV infusion • Side Effects • Infusion reactions • Infections? • PML (progressive multifocal leukoencephalopathy) • Hepatitis B reactivation • Hypogammaglobulinemia • Decreased CD4 counts Tocilizumab (Actemra) • Monoclonal antibody - inhibits IL-6 • Subcutaneous & infusion • Dose modifications for LFTs, platelets, and ANC • Side Effects • Infection • Reactivation of TB • Fungal infections • Reactivation of Hepatitis B • Cytopenias • Increased liver tests • Increased lipids • GI perforations Tofacitinib (Xeljanz) • Inhibits Janus Kinase – involved with T cell signaling/ activation/ proliferation • Oral tablet • Renal & hepatic dosing • Dose modifications: neutropenia, lymphopenia & anemia • Drug interactions • Side Effects • Infection • Reactivation TB • Fungal infections • Cytopenias • GI symptoms; Liver irritation • Elevated lipids • Increased risk for cancer (Lymphoma)? Anakinra (Kineret) • Inhibits IL-1, decreasing inflammation • Daily (perhaps multiple times daily) subcutaneous injection • Limited distribution: • 1 pharmacy • Side Effects • Injection site reactions • Not so much… Questions? PSORIATIC ARTHRITIS Psoriatic arthritis is a type of arthritic inflammation that occurs in about 15 percent [25%?] of patients who have a skin rash called psoriasis. This particular arthritis can affect any joint in the body, and symptoms vary from person to person. The pathophysiology is not clear (or perhaps not the same for all). Abnormalities are similar to rheumatoid arthritis (Antibody, B cells, T cells and cytokines) however there may be similarities to the spondyloarthropathies (like ankylosing spondylitis). https://www.rheumatology.org/Practice/Clinical/Patients/Diseases_And_Conditions/Psoriatic_Arthritis/ Ustekinumab (Stelara) • Human antibody against IL-12 and IL-23 • Subcutaneous injection at week 0, then week 4 then every 12 weeks • Side Effects • URI • Headache • Fatigue • Infection • TB reactivation • Seizures • CNS changes • Increased cancer risk? Secukinumab (Cosentyx) • Monoclonal antibody – inhibits IL-17A • Subcutaneous injection weeks 0,1,2,3 and 4; then every 4 weeks • Side effects • URI • Diarrhea • Reactivation of TB • Worsening of Crohn’s Disease Apremilast (Otezla) • Inhibits phosphodiesterase 4 leading to increased cAMP levels • Downregulatory signal in immune cells • Decreased TNF and IL-17 • Oral tablet • Renal dosing • Drug interactions • Side Effects • Diarrhea, nausea and vomiting • Upper Respiratory Infection • Headache • Worsening depression SYSTEMIC LUPUS ERYTHEMATOSUS Systemic Lupus Erythematosus is an autoimmune disease in which the immune system produces antibodies to cells within the body leading to widespread inflammation and tissue damage. The pathophysiology involves antibody predominantly (and plasma cells and B cells by extension). http://www.cdc.gov/arthritis/basics/lupus.htm Belimumab (Benlysta) • Inhibits B cell activating factor (BAFF) • IV infusion • Side Effects • Infection • Urinary tract infection • Pulmonary infections • Depression • Increased risk for cancer (Lymphoma)? Questions? SCREENING PRIOR TO INITIATION Prior to starting: labs Hep B panel Hep C TB SCr LFTs CBC TNFi x x x x x x abatacept x x x x x x rituximab x x x x x x tocilizumab x x x x x x Medication / Class tofacitinib x x x x x CBC w/ diff (ANC & Plt) x (neutrophils, lymphocytes, anemia) Lipid panel x x Prior to starting: labs Medication / Class Hep B panel Hep C TB anakinra SCr LFTs x x CBC ustekinumab x x x x x x secukinumab x x x x x x apremilast x belimumab x x CBC w/ diff x Lipid panel Prior to starting: medical issues Demyelinating Heart nervous Medication / Cancer Failure system Class disease TNFi x abatacept x x x x Weight x x x x x Serious COPD infections x x x x rituximab x tocilizumab tofacitinib Lupus Recent abdominal surgery / hx of diverticulitis x Prior to starting: Medical issues Medication / Class Cancer Serious infections anakinra x x ustekinumab x x secukinumab Depression x x x Crohn’s Disease x x apremilast belimumab Weight x x Prior to starting: vaccines American College of Rheumatology Recommendations Killed vaccines Pneumococcal DMARD monotherapy Combination DMARDs TNFi biologics Non-TNF biologics X X X X Influenza X X X X Hepatitis Ba Recombinant vaccine Live attenuated vaccine Human Papillomavirusb Herpes zosterc* Before initiating therapy X X X X X X X X X X X X Abbreviations: disease-modifying antirheumatic drugs (DMARDs); tumor necrosis factor inhibitor (TNFi); Rheumatoid arthritis (RA) * Deviates from CDC recommendations a. Given if known hepatitis B risk factors are present (intravenous drug abuse, multiple sex partners in previous six months, health care personnel) b: Human Papillomavirus Vaccine- Given to people who are normally eligible (in individuals 11-26 years old). c: RA patients > 50 years old should receive herpes zoster vaccine prior to starting biologic therapy. Can start therapy 2 weeks after vaccine. Chart adapted by Emily Prinz, Pharm.D., from Figure 8, 2015 American College of Rheumatology Guidelines for the Treatment of Rheumatoid Arthritis. Prior to Starting: other considerations • Pregnancy • Have a discussion: risks vs benefits • RA often improves during pregnancy • Insurance formulary • Ability to self administer injections ON TREATMENT CONSIDERATIONS On treatment: Vaccines American College of Rheumatology Recommendations Killed vaccines Pneumococcal Influenza Hepatitis Ba Recombinant vaccine Live attenuated vaccine Human Papillomavirusb Herpes zosterc* While already taking therapy DMARD monotherapy X X X X X Combination DMARDs X X X X X TNFi biologicsd X X X X X X X X Non-TNFi biologicsd Abbreviations: disease-modifying antirheumatic drugs (DMARDs); tumor necrosis factor inhibitor (TNFi); Rheumatoid arthritis (RA) * Deviates from CDC recommendations a. Given if known hepatitis B risk factors are present (intravenous drug abuse, multiple sex partners in previous six months, health care personnel) b: Human Papillomavirus Vaccine- Given to people who are normally eligible (in individuals 11-26 years old). c: RA patients > 50 years old should receive herpes zoster vaccine prior to starting biologic therapy. Can received therapy 2 weeks after vaccine. d: RA patients currently receiving biologics should not receive live attenuated vaccines Chart adapted by Emily Prinz, Pharm.D., from Figure 8, 2015 American College of Rheumatology Guidelines for the Treatment of Rheumatoid Arthritis. On treatment: labs • Laboratory monitoring • Mostly without recommendations / guidelines • Primarily with clinical suspicion • Tofacitinib: • 4-8 weeks post initiation: CBC w/ diff, LFTs, and lipids • Q3 months: CBC w/ diff, LFTs • Tocilizumab: • 4-8 weeks post initiation: CBC w/ diff, LFTs, and lipids • Q3 months: CBC w/ diff, LFTs • Q6 months: lipids On treatment • Hold the medication for a week (or perhaps two) when fever is present; Patient looks sick • NOT necessary for apremilast • Injection site reactions • Lasts 2-7 days • Usually worse with 2nd and 3rd injection • Usually minimize by 6 weeks • Ensure allowing to warm up prior to administration (30-45 minutes) • Cold pack – before and / or after • Antihistamines • Topical steroids • Rule out skin infection – good hygiene practices for injection On treatment • Perioperative Management • Most recent guidance etanercept adalimumab infliximab golimumab certolizumab tocilizumab subcut tociluzmab IV abatacept subcut abatacept IV rituximab hold 2 weeks hold 3 weeks hold 6 weeks hold 6 weeks hold 6 weeks hold 3 weeks hold 4 weeks hold 2 weeks hold 4 weeks no recommendation to hold Goodman, S. Rheumatoid Arthritis: Perioperative Management of Biologics and DMARDS. Sem Arth and Rheum 2015;44:627-632 Pipeline for rheumatology • Biosimilars: • infliximab, etanercept, & adalimumab – approved by FDA • rituximab – application submitted to FDA • IL-17 inhibitors: brodalumab, ixekizumab (both currently approved for • • • • • • • • • psoriasis) JAK inhibitors: baricitinib, filgotinib IL-6 inhibitors: sarilumab, sirukumab CD20 inhibitor: obinutuzumab CD22 inhibitor: epratuzumab Anti-interferon-α: anifrolumab, sifalimumab BAFF/Blys inhibitor: blisibimod Blys & APRIL inhibitor: atacicept Synthetic cannabinoid: ajulemic acid FCX-013 gene therapy Summary Take Home Points • Infection risk is likely higher in general for biologic agents • Hold the medication for a week (or perhaps two) when • Fever is present • Patient looks sick • Vaccinations are critical to minimize preventable infections • Assess vaccination status at PCP or pharmacy visits • Avoid live-virus vaccines: • No biologic combinations Zoster, Varicella, Measles, Mumps, Rubella, Nasal influenza Questions?