2023 Meeting Magazine - 26

RINVOQ (RIN-VOKE) (upadacitinib) extended-release tablets, for oral use
Ankylosing Spondylitis
®
WARNING: SERIOUS INFECTIONS, MORTALITY, MALIGNANCY,
MAJOR ADVERSE CARDIOVASCULAR EVENTS, and THROMBOSIS
SERIOUS INFECTIONS
Patients treated with RINVOQ are at increased risk for developing
serious infections that may lead to hospitalization or death
[see Warnings and Precautions, Adverse Reactions]. Most
patients who developed these infections were taking concomitant
immunosuppressants such as methotrexate or corticosteroids.
If a serious infection develops, interrupt RINVOQ until the infection
is controlled.
Reported infections include:
* Active tuberculosis, which may present with pulmonary or
extrapulmonary disease. Patients should be tested for latent
tuberculosis before RINVOQ use and during therapy. Treatment
for latent infection should be considered prior to RINVOQ use.
* Invasive fungal infections, including cryptococcosis and
pneumocystosis.
* Bacterial, viral, including herpes zoster, and other infections due
to opportunistic pathogens.
The risks and benefits of treatment with RINVOQ should be carefully
considered prior to initiating therapy in patients with chronic or
recurrent infection.
Patients should be closely monitored for the development of signs
and symptoms of infection during and after treatment with RINVOQ,
including the possible development of tuberculosis in patients who
tested negative for latent tuberculosis infection prior to initiating
therapy [see Warnings and Precautions].
MORTALITY
In a large, randomized, postmarketing safety study in rheumatoid
arthritis (RA) patients 50 years of age and older with at least one
cardiovascular risk factor comparing another Janus kinase (JAK)
inhibitor to tumor necrosis factor (TNF) blockers, a higher rate of
all-cause mortality, including sudden cardiovascular death, was
observed with the JAK inhibitor [see Warnings and Precautions].
MALIGNANCIES
Lymphoma and other malignancies have been observed in patients
treated with RINVOQ. In RA patients treated with another JAK
inhibitor, a higher rate of malignancies (excluding non-melanoma
skin cancer (NMSC)) was observed when compared with TNF
blockers. Patients who are current or past smokers are at additional
increased risk [see Warnings and Precautions].
MAJOR ADVERSE CARDIOVASCULAR EVENTS
In RA patients 50 years of age and older with at least one
cardiovascular risk factor treated with another JAK inhibitor,
a higher rate of major adverse cardiovascular events (MACE)
(defined as cardiovascular death, myocardial infarction, and
stroke), was observed when compared with TNF blockers. Patients
who are current or past smokers are at additional increased risk.
Discontinue RINVOQ in patients that have experienced a myocardial
infarction or stroke [see Warnings and Precautions].
THROMBOSIS
Thrombosis, including deep venous thrombosis, pulmonary
embolism, and arterial thrombosis have occurred in patients
treated with JAK inhibitors used to treat inflammatory conditions.
Many of these adverse events were serious and some resulted
in death. In RA patients 50 years of age and older with at least
one cardiovascular risk factor treated with another JAK inhibitor,
a higher rate of thrombosis was observed when compared with
TNF blockers. Avoid RINVOQ in patients at risk. Patients with
symptoms of thrombosis should discontinue RINVOQ and be
promptly evaluated [see Warnings and Precautions].
INDICATIONS AND USAGE
Rheumatoid Arthritis
RINVOQ® is indicated for the treatment of adults with moderately to severely
active rheumatoid arthritis who have had an inadequate response or
intolerance to one or more TNF blockers.
* Limitations of Use: RINVOQ is not recommended for use in combination
with other JAK inhibitors, biologic disease-modifying antirheumatic
drugs (DMARDs), or with potent immunosuppressants such as
azathioprine and cyclosporine.
Psoriatic Arthritis
RINVOQ is indicated for the treatment of adults with active psoriatic
arthritis who have had an inadequate response or intolerance to one or
more TNF blockers.
* Limitations of Use: RINVOQ is not recommended for use in
combination with other JAK inhibitors, biologic DMARDs, or with potent
immunosuppressants such as azathioprine and cyclosporine.
Atopic Dermatitis
RINVOQ is indicated for the treatment of adults and pediatric patients
12 years of age and older with refractory, moderate to severe atopic
dermatitis whose disease is not adequately controlled with other
systemic drug products, including biologics, or when use of those
therapies are inadvisable.
* Limitations of Use: RINVOQ is not recommended for use in combination
with other JAK inhibitors, biologic immunomodulators, or with other
immunosuppressants.
Ulcerative Colitis
RINVOQ is indicated for the treatment of adult patients with moderately to
severely active ulcerative colitis who have had an inadequate response or
intolerance to one or more TNF blockers.
* Limitations of Use: RINVOQ is not recommended for use in combination
with other JAK inhibitors, biological therapies for ulcerative colitis, or with
potent immunosuppressants such as azathioprine and cyclosporine.
Crohn's Disease
RINVOQ is indicated for the treatment of adult patients with moderately to
severely active Crohn's disease who have had an inadequate response or
intolerance to one or more TNF blockers.
* Limitations of Use: RINVOQ is not recommended for use in combination
with other JAK inhibitors, biological therapies for Crohn's disease, or with
potent immunosuppressants such as azathioprine and cyclosporine.
PROFESSIONAL BRIEF SUMMARY
CONSULT PACKAGE INSERT FOR FULL PRESCRIBING INFORMATION
RINVOQ is indicated for the treatment of adults with active ankylosing
spondylitis who have had an inadequate response or intolerance to one or
more TNF blockers.
* Limitations of Use: RINVOQ is not recommended for use in
combination with other JAK inhibitors, biologic DMARDs, or with potent
immunosuppressants such as azathioprine and cyclosporine.
Non-radiographic Axial Spondyloarthritis
RINVOQ is indicated for the treatment of adults with active non-radiographic
axial spondyloarthritis with objective signs of inflammation who have had an
inadequate response or intolerance to TNF blocker therapy.
* Limitations of Use: RINVOQ is not recommended for use in
combination with other JAK inhibitors, biologic DMARDs, or with potent
immunosuppressants such as azathioprine and cyclosporine.
CONTRAINDICATIONS
RINVOQ is contraindicated in patients with known hypersensitivity to
upadacitinib or any of its excipients [see Warnings and Precautions].
WARNINGS AND PRECAUTIONS
Serious Infections
Serious and sometimes fatal infections have been reported in patients
receiving RINVOQ. The most frequent serious infections reported with
RINVOQ included pneumonia and cellulitis [see Adverse Reactions]. Among
opportunistic infections, tuberculosis, multidermatomal herpes zoster, oral/
esophageal candidiasis, and cryptococcosis, were reported with RINVOQ.
Avoid use of RINVOQ in patients with an active, serious infection, including
localized infections. Consider the risks and benefits of treatment prior to
initiating RINVOQ in patients:
* with chronic or recurrent infection
* who have been exposed to tuberculosis
* with a history of a serious or an opportunistic infection
* who have resided or traveled in areas of endemic tuberculosis or
endemic mycoses; or
* with underlying conditions that may predispose them to infection.
Closely monitor patients for the development of signs and symptoms of
infection during and after treatment with RINVOQ. Interrupt RINVOQ if a
patient develops a serious or opportunistic infection.
A patient who develops a new infection during treatment with RINVOQ
should undergo prompt and complete diagnostic testing appropriate for an
immunocompromised patient; appropriate antimicrobial therapy should be
initiated, the patient should be closely monitored, and RINVOQ should be
interrupted if the patient is not responding to antimicrobial therapy. RINVOQ
may be resumed once the infection is controlled.
Tuberculosis
Evaluate and test patients for latent and active tuberculosis (TB) infection
prior to administration of RINVOQ. Patients with latent TB should be treated
with standard antimycobacterial therapy before initiating RINVOQ. RINVOQ
should not be given to patients with active TB. Consider anti-TB therapy
prior to initiation of RINVOQ in patients with previously untreated latent TB
or active TB in whom an adequate course of treatment cannot be confirmed,
and for patients with a negative test for latent TB but who have risk factors
for TB infection.
Consultation with a physician with expertise in the treatment of TB is
recommended to aid in the decision about whether initiating anti-TB therapy
is appropriate for an individual patient.
During RINVOQ use, monitor patients for the development of signs and
symptoms of TB, including patients who tested negative for latent TB
infection prior to initiating therapy.
Viral Reactivation
Viral reactivation, including cases of herpes virus reactivation (e.g., herpes
zoster) and hepatitis B virus reactivation, were reported in clinical trials with
RINVOQ [see Adverse Reactions]. The risk of herpes zoster appears to be
higher in patients treated with RINVOQ in Japan. If a patient develops herpes
zoster, consider temporarily interrupting RINVOQ until the episode resolves.
Screening for viral hepatitis and monitoring for reactivation should be
performed in accordance with clinical guidelines before starting and during
therapy with RINVOQ. Patients who were positive for hepatitis C antibody
and hepatitis C virus RNA, were excluded from clinical trials. Patients who
were positive for hepatitis B surface antigen or hepatitis B virus DNA were
excluded from clinical trials. However, cases of hepatitis B reactivation
were still reported in patients enrolled in the Phase 3 trials of RINVOQ. If
hepatitis B virus DNA is detected while receiving RINVOQ, a liver specialist
should be consulted.
Mortality
In a large, randomized, postmarketing safety study of another JAK inhibitor
in RA patients 50 years of age and older with at least one cardiovascular risk
factor, a higher rate of all-cause mortality, including sudden cardiovascular
death, was observed in patients treated with the JAK inhibitor compared
with TNF blockers.
Consider the benefits and risks for the individual patient prior to initiating or
continuing therapy with RINVOQ.
Malignancy and Lymphoproliferative Disorders
Malignancies, including lymphomas, were observed in clinical trials of
RINVOQ [see Adverse Reactions].
In a large, randomized, postmarketing safety study of another JAK inhibitor
in RA patients, a higher rate of malignancies (excluding NMSC) was
observed in patients treated with the JAK inhibitor compared to those
treated with TNF blockers. A higher rate of lymphomas was observed in
patients treated with the JAK inhibitor compared to those treated with
TNF blockers. A higher rate of lung cancers was observed in current or
past smokers treated with the JAK inhibitor compared to those treated
with TNF blockers. In this study, current or past smokers had an additional
increased risk of overall malignancies.
Consider the benefits and risks for the individual patient prior to initiating
or continuing therapy with RINVOQ, particularly in patients with a known
malignancy (other than a successfully treated NMSC), patients who
develop a malignancy when on treatment, and patients who are current
or past smokers.
Non-Melanoma Skin Cancer
NMSCs have been reported in patients treated with RINVOQ. Periodic skin
examination is recommended for patients who are at increased risk for
skin cancer.
Exposure to sunlight and UV light should be limited by wearing protective
clothing and using a broad-spectrum sunscreen.
Major Adverse Cardiovascular Events
In a large, randomized, postmarketing safety study of another JAK inhibitor
in RA patients 50 years of age and older with at least one cardiovascular risk
factor, a higher rate of major adverse cardiovascular events (MACE) defined
as cardiovascular death, non-fatal myocardial infarction (MI), and non-fatal
stroke was observed with the JAK inhibitor compared to those treated 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 RINVOQ, particularly in patients who are current or
past smokers and patients with other cardiovascular risk factors. Patients
should be informed about the symptoms of serious cardiovascular events
and the steps to take if they occur. Discontinue RINVOQ in patients that have
experienced a myocardial infarction or stroke.
Thrombosis
Thrombosis, including deep venous thrombosis (DVT), pulmonary embolism
(PE), and arterial thrombosis, have occurred in patients treated for
inflammatory conditions with JAK inhibitors, including RINVOQ. Many of
these adverse events were serious and some resulted in death.
In a large, randomized, postmarketing safety study of another JAK inhibitor
in RA patients 50 years of age and older with at least one cardiovascular
risk factor, higher rates of overall thrombosis, DVT, and PE were observed
compared to those treated with TNF blockers.
If symptoms of thrombosis occur, patients should discontinue RINVOQ and
be evaluated promptly and treated appropriately. Avoid RINVOQ in patients
that may be at increased risk of thrombosis.
Hypersensitivity Reactions
Serious hypersensitivity reactions such as anaphylaxis and angioedema
were reported in patients receiving RINVOQ in clinical trials. If a clinically
significant hypersensitivity reaction occurs, discontinue RINVOQ and institute
appropriate therapy [see Adverse Reactions].
Gastrointestinal Perforations
Gastrointestinal perforations have been reported in clinical trials with
RINVOQ [see Adverse Reactions].
Monitor RINVOQ-treated patients who may be at risk for gastrointestinal
perforation (e.g., patients with a history of diverticulitis and those taking
concomitant medications including NSAIDs or corticosteroids). Evaluate
promptly patients presenting with new onset abdominal pain for early
identification of gastrointestinal perforation.
Laboratory Abnormalities
Neutropenia
Treatment with RINVOQ was associated with an increased incidence of
neutropenia (ANC less than 1000 cells/mm3).
Evaluate neutrophil counts at baseline and thereafter according to routine
patient management. Avoid RINVOQ initiation and interrupt RINVOQ
treatment in patients with a low neutrophil count (i.e., ANC less than
1000 cells/mm3).
Lymphopenia
ALC less than 500 cells/mm3 were reported in RINVOQ-treated patients in
clinical trials.
Evaluate lymphocyte counts at baseline and thereafter according to routine
patient management. Avoid RINVOQ initiation or interrupt RINVOQ treatment
in patients with a low lymphocyte count (i.e., less than 500 cells/mm3).
Anemia
Decreases in hemoglobin levels to less than 8 g/dL were reported in
RINVOQ-treated patients in clinical trials.
Evaluate hemoglobin at baseline and thereafter according to routine patient
management. Avoid RINVOQ initiation or interrupt RINVOQ treatment in
patients with a low hemoglobin level (i.e., less than 8 g/dL).
Lipids
Treatment with RINVOQ was associated with increases in lipid parameters,
including total cholesterol, low-density lipoprotein (LDL) cholesterol,
and high-density lipoprotein (HDL) cholesterol [see Adverse Reactions].
Elevations in LDL cholesterol decreased to pre-treatment levels in response
to statin therapy. The effect of these lipid parameter elevations on
cardiovascular morbidity and mortality has not been determined.
Assess lipid parameters approximately 12 weeks after initiation of
treatment, and thereafter according to the clinical guidelines for
hyperlipidemia. Manage patients according to clinical guidelines for the
management of hyperlipidemia.
Liver Enzyme Elevations
Treatment with RINVOQ was associated with increased incidence of liver
enzyme elevations compared to treatment with placebo.
Evaluate liver enzymes at baseline and thereafter according to routine
patient management. Prompt investigation of the cause of liver enzyme
elevation is recommended to identify potential cases of drug-induced
liver injury.
If increases in ALT or AST are observed during routine patient management
and drug-induced liver injury is suspected, RINVOQ should be interrupted
until this diagnosis is excluded.
Embryo-Fetal Toxicity
Based on findings in animal studies, RINVOQ may cause fetal harm when
administered to a pregnant woman. Administration of upadacitinib to rats
and rabbits during organogenesis caused increases in fetal malformations.
Verify the pregnancy status of patients of reproductive potential prior to
starting treatment. Advise females of reproductive potential of the potential
risk to the fetus and to use effective contraception during treatment with
RINVOQ and for 4 weeks following completion of therapy [see Use in
Specific Populations].
Vaccinations
Avoid use of live vaccines during or immediately prior to RINVOQ therapy
initiation. Prior to initiating RINVOQ, 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 RINVOQ. Most reports described anatomic (e.g., ileostomy,
colostomy, intestinal resection) or functional gastrointestinal conditions
https://www.rinvoqhcp.com/
2023 Meeting Magazine

Table of Contents for the Digital Edition of 2023 Meeting Magazine
