The Medical Letter. on Drugs and Therapeutics

Transcription

1 The Medical Letter publications are protected by US and international copyright laws. Forwarding, copying or any other distribution of this material is strictly prohibited. For further information call: Last updated: July 30, 2018 The Medical Letter on Drugs and Therapeutics Expanded Table: Some Biologic Agents and JAK Inhibitors for RA Some Biologic Agents and JAK Inhibitors for Rheumatoid Arthritis Tumor Necrosis Factor (TNF) Inhibitors Adalimumab Humira (Abbvie) biosimilar Cyltezo (Boehringer Ingelheim; not yet marketed) Certolizumab pegol Cimzia (UCB) Etanercept Enbrel (Amgen) Golimumab Simponi (Janssen) Simponi Aria 10 mg/0.1 ml, 10 mg/ 0.2 ml, 20 mg/0.2 ml, 20 mg/0.4 ml syringes; 40 mg/0.8 ml prefilled pens and syringes 200 mg single-dose vials; 200 mg/ml syringes 25 mg multiple-dose vials; 25 mg/0.5 ml, 50 mg/ml syringes; 50 mg/ml autoinjectors 50 mg/0.5 ml, 100 mg/ ml syringes and auto-injectors 50 mg single-dose vials 40 mg SC q2 wks Generally considered safe for use during pregnancy Initial: 400 mg SC at 0, 2, and 4 wks Maintenance: 200 mg SC every other wk or 400 mg SC q4 wks 25 mg SC 2x/wk or 50 mg SC once/wk 50 mg SC once/month Initial: 2 mg/kg IV at 0 and 4 wks Maintenance: 2 mg/kg IV q8 wks Placental transfer of anti-tnf antibodies is higher in the late second and third trimesters, especially with infliximab, adalimumab, and golimumab Injection-site reactions are common with adalimumab, certolizumab pegol, etanercept, and golimumab Infusion reactions including fever, urticaria, dyspnea, and hypotension can occur with infliximab and golimumab Cytopenias can occur with all TNF inhibitors Malignancies, especially lymphomas, have been, but a cause-andeffect relationship has not been established (continued on next page) Infliximab and golimumab are FDA-approved for treatment of RA only for use with methotrexate Combining a biologic agent with a conventional DMARD is recommended for patients with moderate to high disease activity and for those who have had an inadequate response to a conventional DMARD alone Combining different biologic agents or a biologic agent and a JAK inhibitor increases the risk of infection and is not recommended Have been shown to relieve symptoms and may be more effective than methotrexate alone in limiting joint destruction Use in combination with methotrexate has synergistic beneficial effects TNF inhibitors appear to be similar in efficacy; no headto-head trials comparing them are (continued on next page) $ N.A e130

2 Tumor Necrosis Factor (TNF) Inhibitors (continued) Infliximab Remicade (Janssen) biosimilar Inflectra (Celltrion) Renflexis (Merck) Ixifi (Pfizer; not yet marketed) 100 mg single-dose vials Initial: 3 mg/kg IV at 0, 2, and 6 wks Maintenance: 3 mg/kg IV q8 wks Some patients may require higher maintenance doses (up to 10 mg/ kg every 8 wks) or more frequent doses (up to every 4 wks) Generally considered safe for use during pregnancy Placental transfer of anti-tnf antibodies is higher in the late second and third trimesters, especially with infliximab, adalimumab, and golimumab (see previous page) Increased risk of infections, including reactivated and disseminated tuberculosis, invasive or disseminated fungal infection, and other opportunistic infections Reactivation of HBV Rarely induces or exacerbates heart failure or induces a reversible lupuslike syndrome Demyelinating conditions, including multiple sclerosis, optic neuritis, and Guillain-Barré syndrome have been (see previous page) Patients who do not respond to one TNF inhibitor may respond to another Have a faster onset of action than conventional DMARDs; some patients report substantial improvement after the first dose Tuberculin skin testing or interferon-gamma release assay is recommended before starting and periodically during treatment Serologic testing for active hepatitis B infection is recommended before starting treatment Antiviral prophylaxis against reactivation of HBV may be appropriate in some patients Patients with pre-existing demyelinating conditions should not be treated with TNF inhibitors Etanercept has a rapid onset of action and a short halflife that makes toxicity, if it occurs, relatively short-lived Golimumab has been shown to be effective in some patients who did not respond to infliximab or etanercept $ N.A. e131

3 Interleukin (IL-6) Inhibitors Sarilumab Kevzara (Sanofi/Regeneron) Tocilizumab Actemra (Genentech) 150 mg/1.14 ml, 200 mg/1.14 ml prefilled pens and syringes 80, 200, 400 mg singledose vials 162 mg/0.9 ml syringes 200 mg SC q2 wks No adequate data on use Initial: 4 mg/kg IV q4 wks Maintenance: 8 mg/kg IV q4 wks Initial: 162 mg SC every other wk (every wk for patients weighing 100 kg) Maintenance: 162 mg SC once/wk (can be administered once every other wk in patients who weigh <100 kg) Infusion reactions, hypertension, neutropenia, elevated serum transaminase levels, and dyslipidemia can occur Serious infections and hypersensitivity reactions, including anaphylaxis, can occur An increase in lower GI tract perforations, especially in patients with diverticulitis, has been with tocilizumab FDA-approved for use in patients who have had an inadequate response or intolerance to 1 DMARDs Combining a biologic agent with a conventional DMARD is recommended for patients with moderate to high disease activity and for those who have had an inadequate response to a conventional DMARD alone Combining different biologic agents or a biologic agent and a JAK inhibitor increases the risk of infection and is not recommended Sarilumab has been effective in combination with methotrexate in patients who had not responded to methotrexate or a TNF inhibitor Sarilumab monotherapy has been shown to be more effective than adalimumab in patients who had not responded to or could not tolerate methotrexate Tocilizumab monotherapy may be as effective as combination therapy with methotrexate in patients with active RA despite methotrexate therapy Clinical improvement has occurred as early as two weeks after starting tocilizumab monotherapy Tocilizumab monotherapy has been shown to be more effective than adalimumab in reducing disease activity scores No studies comparing sarilumab with tocilizumab are Monitoring of complete blood counts and liver enzymes is recommended $ e132

4 Other Biologic Agents Rituximab Rituxan (Genentech) 100, 500 mg single-use vials 1000 mg IV twice, 2 wks apart No adequate data on use Rituximab crosses the placenta and has been detected in the newborn B-cell lymphocytopenia has been in infants born to women who took the drug during pregnancy Anaphylaxis and anaphylactoid reactions can occur within 2 hours of infusion PML due to JC virus, which often causes death or severe neurological disability, has been Reactivation of HBV FDA-approved only for use with methotrexate in patients who have had an inadequate response to 1 TNF inhibitors Has been effective in patients with RA who had an inadequate response to methotrexate and/or a TNF inhibitor Patients can be retreated every 4-6 months IV methylprednisolone 100 mg or its equivalent infused 30 minutes before rituximab can reduce the incidence and severity of infusion reactions Patients at high risk for hepatitis B infection should be screened for the disease before starting treatment Antiviral prophylaxis against reactivation of HBV may be appropriate in some patients $18, Abatacept Orencia (BMS) 250 mg single-use vials 50 mg/0.4 ml, 87.5 mg/ 0.7 ml, 125 mg/ml syringes; 125 mg/ml auto-injectors <60 kg: 500 mg IV at 0, 2, and kg: 750 mg IV at 0, 2, and 4 >100 kg: 1000 mg IV at 0, 2, and mg SC once/wk 5 No adequate data on use Hypertension, headache, and dizziness can occur Anaphylactoid reactions can occur within 1 hour after the start of infusion May increase the risk of serious infections such as pneumonia, pyelonephritis, cellulitis, and diverticulitis Can be used as monotherapy or in combination with a conventional DMARD Monotherapy has been effective for treatment of RA that had not responded to methotrexate or TNF inhibitors Anakinra Kineret (Sobi) 100 mg/0.67 ml syringes 100 mg SC once/d No adequate data on use Injection-site reactions, headache, vomiting, infections, arthralgia, and nasopharyngitis have been FDA-approved for use in patients who have had an inadequate response or intolerance to 1 DMARDs Least commonly used biologic DMARD Limited evidence of efficacy compared to other biologics e133

5 Janus Kinase (JAK) Inhibitors Baricitinib Olumiant (Lilly) Tofacitinib Xeljanz (Pfizer) Xeljanz XR 2 mg tabs 2 mg PO once/d No adequate data on use 5 mg tabs 11 mg ER tabs 5 mg PO bid 11 mg PO once/d Upper respiratory tract infections and nausea are common Elevated hepatic transaminases, dyslipidemia, and cytopenias have been Thromboembolic events, malignancy, and GI perforations have been Infections, especially herpes zoster and tuberculosis, can occur Diarrhea, nasopharyngitis, upper respiratory tract infections, headache, and hypertension are common Elevated hepatic transaminases, dyslipidemia, and cytopenias have been Infections, especially herpes zoster and tuberculosis, can occur An increased incidence of solid cancers was detected in short-term ( 12 months) clinical trials Baricitinib is FDA-approved for use in patients who have had an inadequate response to 1 TNF inhibitors Tofacitinib is FDA-approved for use in patients who have had an inadequate response or intolerance to methotrexate Generally reserved for treatment of patients with moderate or high disease activity Combining a biologic agent and a JAK inhibitor increases the risk of infection and is not recommended First-line treatment with tofacitinib was superior to methotrexate in reducing the signs and symptoms of RA and in slowing progression of joint damage Efficacy of tofacitinib plus methotrexate is comparable to that of adalimumab plus methotrexate Baricitinib was more effective than placebo in patients with moderately to severely active RA that had not responded to one or more TNF inhibitors No studies comparing tofacitinib with baricitinib are Monitoring of complete blood counts is recommended ER = extended-release; N.A. = cost not yet ; PML = progressive multifocal leukoencephalopathy; HBV = hepatitis B virus 1. Dosage adjustment may be needed for hepatic or renal impairment. 2. Approximate WAC for 30 days or 4 weeks treatment with the usual dosage or lowest usual maintenance dosage (for a 70-kg patient treated with some parenteral drugs). WAC = wholesaler acquisition cost or manufacturer s published price to wholesalers; WAC represents a published catalogue or list price and may not represent an actual transactional price. Source: AnalySource Monthly. July 5, Reprinted with permission by First Databank, Inc. All rights reserved Cost for 8 weeks treatment. 4. Cost of two 1000-mg doses. 5. If administered after an initial IV loading dose, the first 125-mg SC injection should be given within a day of the IV loading dose. $ e134