Long-Term Efficacy and Safety of a JAKi in RA
Video
Dr. Stan Cohen shares his clinical perspective on upadacitinib data in patients with RA
- 11-minute watch
The expert
Stanley Cohen, MD
- Physician, Rheumatology Associates
- Clinical Professor in the Department of Internal Medicine at UT Southwestern Medical Center
- Co-Director of the Division of Rheumatology at Presbyterian Hospital, Dallas
- Co-Medical Director of Metroplex Clinical Research Center
- Past President, American College of Rheumatology
Key information
RA was the first indication for upadacitinib4,5
In an integrated RA safety analysis,4,6
AD, atopic dermatitis; AS, ankylosing spondylitis; bDMARD-IR, inadequate response or intolerance to biological disease-modifying antirheumatic drug; CD, Crohn’s disease; FDA, US Food & Drug Administration; JAKi, Janus kinase inhibitor; nr-axSpA, non-radiographic axial spondyloarthritis; PsA, psoriatic arthritis; PY, patient-year; QD, once-daily; RA, rheumatoid arthritis; RCT, randomized clinical trial; TNFi-IR, inadequate response or intolerance to tumor necrosis factor inhibitors; UC, ulcerative colitis; UPA, upadacitinib.
When considering what treatment to use in your patients, does long-term efficacy and safety data play an important role?
How likely are you to discuss long-term efficacy and safety with your patients with RA when considering JAKi treatment in patients who are TNFi-IR?
Do you feel confident in your ability to discuss the benefit vs. risk of upadacitinib with your patients with RA who are TNFi-IR?
Indications
Upadacitinib is a Janus kinase (JAK) inhibitor indicated for the treatment of:
Adults with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response or intolerance to one or more tumor necrosis factor (TNF) blockers.
Adults with active psoriatic arthritis (PsA) who have had an inadequate response or intolerance to one or more TNF blockers.
Adults with active ankylosing spondylitis (AS) who have had an inadequate response or intolerance to one or more TNF blockers.
Adults with active non-radiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation who have had an inadequate response or intolerance to TNF blocker therapy.
- Limitations of Use for RA, PsA, AS and nr-axSpA: Upadacitinib is not recommended for use in combination with other JAK inhibitors, biologic disease-modifying antirheumatic drugs (bDMARDs), or with potent immunosuppressants such as azathioprine and cyclosporine.
Adults and pediatric patients 12 years of age and older with refractory moderate to severe atopic dermatitis (AD) whose disease is not adequately controlled with other systemic drug products, including biologics, or when use of those therapies are inadvisable.
- Limitations of Use for AD: Upadacitinib is not recommended for use in combination with other JAK inhibitors, biologic immunomodulators, or with other immunosuppressants.
Adults with moderately to severely active ulcerative colitis (UC) who have had an inadequate response or intolerance to one or more TNF blockers.
Adults with moderately to severely active Crohn’s disease (CD) who have had an inadequate response or intolerance to one or more TNF blockers.
- Limitations of Use for UC and CD: Upadacitinib is not recommended for use in combination with other JAK inhibitors, biological therapies for UC or CD, respectively, or with potent immunosuppressants such as azathioprine and cyclosporine.
Important safety considerations and boxed warning
Serious Infections: Patients treated with upadacitinib are at increased risk for developing serious infections that may lead to hospitalization or death. These infections include tuberculosis (TB), invasive fungal, bacterial, viral, and other infections due to opportunistic pathogens. Most patients who developed these infections were taking concomitant immunosuppressants, such as methotrexate or corticosteroids. Test for latent TB before and during therapy; treat latent TB prior to use. Consider the risks and benefits prior to initiating therapy in patients with chronic or recurrent infection. If a serious infection develops, interrupt upadacitinib until the infection is controlled.
Mortality: In a postmarketing safety study in RA patients ≥ 50 years of age with at least one cardiovascular (CV) risk factor comparing another JAK inhibitor to TNF blockers, a higher rate of all-cause mortality, including sudden CV death, was observed with the JAK inhibitor.
Malignancies: Malignancies have been observed in upadacitinib treated patients. In RA patients treated with another JAK inhibitor, a higher rate of lymphomas and lung cancers was observed when compared with TNF blockers. Patients who are current or past smokers are at additional increased risk. Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with upadacitinib, particularly in patients with a known malignancy (other than a successfully treated non-melanoma skin cancer [NMSC]), patients who develop a malignancy when on treatment, and patients who are current or past smokers. NMSCs have been reported in patients treated with upadacitinib. Periodic skin examination is recommended for patients who are at increased risk for skin cancer. Advise patients to limit sunlight exposure by wearing protective clothing and using sunscreen.
Major Adverse Cardiovascular Events (MACE): In RA patients who were ≥ 50 years of age with at least one CV risk factor treated with another JAK inhibitor, a higher rate of MACE (CV death, myocardial infarction, and stroke) was observed compared with TNF blockers. Patients who are current or past smokers are at additional increased risk. Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with upadacitinib. Patients should be informed about the symptoms of serious CV events and the steps to take if they occur. Discontinue upadacitinib in patients that have experienced a myocardial infarction or stroke.
Thrombosis: Thrombosis, including deep vein thrombosis, pulmonary embolism, and arterial thrombosis, have occurred in patients treated with JAK inhibitors, including upadacitinib. Many of these adverse events were serious and some resulted in death. In RA patients who were ≥ 50 years of age with at least one CV risk factor treated with another JAK inhibitor, a higher rate of thrombosis was observed when compared with TNF blockers. Avoid upadacitinib in patients at risk. Patients with symptoms of thrombosis should discontinue upadacitinib and be promptly evaluated.
Hypersensitivity Reactions: Upadacitinib is contraindicated in patients with known hypersensitivity to upadacitinib or any of its excipients. Serious hypersensitivity reactions such as anaphylaxis and angioedema were reported in patients receiving upadacitinib in clinical trials. If a clinically significant hypersensitivity reaction occurs, discontinue upadacitinib and institute appropriate therapy.
Other Serious Adverse Reactions: Patients treated with upadacitinib also may be at risk for other serious adverse reactions, including gastrointestinal perforations, neutropenia, lymphopenia, anemia, lipid elevations, liver enzyme elevations, and embryo-fetal toxicity.
Vaccinations: Avoid use of live vaccines during, or immediately prior to, upadacitinib therapy. Prior to initiating upadacitinib, it is recommended that patients be brought up to date with all immunizations, including varicella zoster or prophylactic herpes zoster vaccinations, in agreement with current immunization guidelines.
Medication Residue in Stool: Reports of medication residue in stool or ostomy output have occurred in patients taking upadacitinib. Most reports described patients with shortened gastrointestinal transit times. Instruct patients to contact their healthcare provider if medication residue is observed repeatedly.
Common Adverse Reactions in RA, PsA, AS and nr-axSpA: The most common adverse reactions (≥1%) were upper respiratory tract infections, herpes zoster, herpes simplex, bronchitis, nausea, cough, pyrexia, acne, and headache.
Common Adverse Reactions in AD: The most common adverse reactions (≥1%) are upper respiratory tract infections, acne, herpes simplex, headache, increased blood creatine phosphokinase, cough, hypersensitivity, folliculitis, nausea, abdominal pain, pyrexia, increased weight, herpes zoster, influenza, fatigue, neutropenia, myalgia, and influenza like illness.
Common Adverse Reactions in UC: The most common adverse reactions (≥5%) reported are upper respiratory tract infections, increased blood creatine phosphokinase, acne, neutropenia, elevated liver enzymes, and rash.
Common Adverse Reactions in CD: The most common adverse reactions (≥5%) reported are upper respiratory tract infections, anemia, pyrexia, acne, herpes zoster, and headache.
Review accompanying upadacitinib full Prescribing Information for additional information, visit www.rxabbvie.com or contact AbbVie Medical Information at 1-800-633-9110.
Explore more posts about patients with RA:
Heart to Heart: Experts Discuss Cardiovascular Risk in Rheumatoid Arthritis
Perspectives on the Safety of a JAK Inhibitor
Long-term JAK Inhibitor Treatment for Rheumatoid Arthritis (RA)
1. RINVOQ (upadacitinib) [package insert]. North Chicago, IL: AbbVie Inc.
2. Data on file, AbbVie Inc. ABVRRTI74922.
3. Data on file, AbbVie Inc. ABVRRTI75992.
4. Data on file, AbbVie Inc. ABVRRTI74946.
5. Fleischmann R, Meerwein S, Charles-Schoeman C, et al. Safety and efficacy of upadacitinib in patients with rheumatoid arthritis and inadequate response or intolerance to biologic DMARDs: Results through 5 years from the SELECT-BEYOND study. Poster presented at: ACR Convergence 2022; November 10–14, 2022; Philadelphia, PA. Poster 0294.
6. Cohen SB, van Vollenhoven R, Curtis JR, et al. Safety profile of upadacitinib up to 6.5 years of exposure in patients with rheumatoid arthritis. Abstract presented at: European Alliance of Associations for Rheumatology 2023; May 31–June 3, 2023; Milan, Italy. Abstract 2415.