For moderate to severe rheumatoid arthritis (RA) in adult TNFi‑IR patients1
For active psoriatic arthritis (PsA) in adult TNFi‑IR patients1
For active ankylosing spondylitis (AS)
in adult TNFi‑IR patients1

SAFETY DATA
FROM 10 TRIALS ACROSS
RA, PSA AND AS1,2,*

>6,800
patients evaluated on
upadacitinib1-4,
as of 6/30/2020

>6,800
patients evaluated on upadacitinib1-4,
as of 6/30/2020

>8,800
patient-years of exposure
to RINVOQ 15 mg1-4,
as of 6/30/2020

~4.5 Years
maximum exposure in RA (~2.6 yrs median),
~3 years max. exposure in PsA (~1.3 yrs median)
and ~2.3 years max. exposure in AS
(~1.7 yrs median) to RINVOQ 15 mg2,3,5,§
as of 6/30/2020

Clinical Trial Overview

SELECT-AXIS 2 Study Design Intro:1,6
14-week, double-blind, parallel-group, placebo-controlled Phase 3 study of 420 patients with active AS who had an intolerance or inadequate response to at least two NSAIDs and 1 or 2 bDMARDs. Patients were randomized to receive RINVOQ 15 mg once daily or placebo. Patients could continue background NSAIDs. The primary endpoint was proportion of patients achieving ASAS40 response at Week 14 vs placebo.

SELECT-AXIS 1 Study Design Intro:1,8
14-week, double-blind, multicenter, parallel-group, placebo-controlled study of 187 adult patients with active AS who had an inadequate response or intolerance to at least two NSAIDs and were bDMARD-naive. Patients were randomized to receive RINVOQ 15 mg or placebo. The primary endpoint was the proportion of patients who achieved an ASAS40 response at Week 14.

SELECT-PsA 1 Study Design Intro:1
24-week, double-blind, active placebo and comparator-controlled study of 1705 adult patients with moderate to severe PsA who had an inadequate response or intolerance to at least one non-biologic DMARD. Patients were randomized to receive either upadacitinib, active comparator, or placebo. The primary endpoint was proportion of patients achieving ACR20 response at Week 12 vs placebo.

SELECT-PsA 2 Study Design Intro:1
24-week, double-blind, placebo-controlled study of 642 adult patients with moderate to severe active PsA who had an inadequate response or intolerance to at least one biologic DMARD. Patients were randomized to receive upadacitinib or placebo. The primary endpoint was proportion of patients achieving ACR20 response at Week 12 vs placebo.

SELECT-EARLY (Study RA-I) Study Design Intro:1,9
48-week, double-blind, active comparator-controlled study of 947 adult patients with moderate to severe RA who were MTX‑naïve. Patients were randomized to receive RINVOQ 15 mg once daily (n=317) or MTX (n=314). The primary endpoint was ACR50 response at Week 12. At Week 26, non-responding patients were rescued according to prespecified criteria.

SELECT-MONOTHERAPY (Study RA-II) Study Design Intro:1,10
14-week, double-blind, active comparator-controlled study of 648 adult patients with moderate to severe RA who had an inadequate response to MTX. Patients were randomized to receive RINVOQ 15 mg once daily (n=217) or cMTX weekly (n=216). The primary endpoint was ACR20 response at Week 14.

SELECT-NEXT (Study RA-III) Study Design Intro:1,11
12-week, double-blind, placebo-controlled study of 661 adult patients with moderate to severe RA who had an inadequate response to csDMARDs. Patients on background csDMARDs were randomized to receive RINVOQ 15 mg once daily (n=221) or placebo (n=221). The primary endpoint was ACR20 response at Week 12.

SELECT-BEYOND (Study RA-V) Study Design Intro:1,12
12-week, double-blind, placebo-controlled study of 499 adult patients with moderate to severe RA who have had an inadequate response or intolerance to biological DMARDs. Patients on background csDMARDs were randomized to receive RINVOQ
15 mg once daily (n=164) or placebo (n=169). The primary endpoint was ACR20 response at Week 12.

SELECT-COMPARE (Study RA-IV) Study Design Intro:1,13
48-week, double-blind, active comparator-controlled study of 1629 adult patients with moderate to severe RA who had an inadequate response to MTX. Patients on background MTX were randomized to receive RINVOQ 15 mg once daily (n=651), placebo (n=651), or active comparator (n=327). The primary endpoint was ACR20 response at Week 12 vs placebo. Prespecified blinded rescue protocols occurred at Weeks 14, 18, 22, or 26.

SELECT-CHOICE Study Design Intro:14
24-week, double-blind, active comparator-controlled study of 612 adult patients with moderate to severe RA who had an inadequate response or intolerance to bDMARDs. Patients on stable csDMARDs were randomized to receive RINVOQ 15 mg once daily (n=303) or active comparator at 0, 2, and 4 weeks, and every 4 weeks thereafter (n=309). The primary endpoint was ΔDAS28-CRP (noninferiority) at Week 12.

Safety Profile
in SELECT-AXIS 2 and
Select-AXIS 11,6,8,15

Safety data at Week 14

Adverse events of special interest6,8,15

SELECT-AXIS 1 & SELECT-AXIS-2: Safety Data SELECT-AXIS 1 & SELECT-AXIS-2: Safety Data SELECT-AXIS 1 & SELECT-AXIS-2: Safety Data

Adverse reaction rates observed in clinical trials and LTE studies may not predict rates observed in clinical practice.

AbbVie is conducting long-term safety studies, including post-marketing studies, to continue to evaluate the safety of RINVOQ. Certain adverse events may require longer observation periods and larger patient exposure to ascertain risk.

SAFETY CONSIDERATIONS

Consider the benefits and risks for the individual patient prior to initiating therapy with RINVOQ

WARNINGS AND PRECAUTIONS

SERIOUS INFECTIONS

Patients treated with RINVOQ are at increased risk for developing infections that may lead to hospitalization or death. These infections include tuberculosis (TB) and 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. If a serious infection develops, interrupt RINVOQ until the infection is controlled.

Carefully consider the risks and benefits of treatment with RINVOQ prior to initiating therapy in patients with chronic or recurrent infection. Monitor patients closely for the development of signs and symptoms of infection during and after treatment with RINVOQ, including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy.

MORTALITY

In a large, randomized, postmarketing safety study comparing another Janus kinase (JAK) inhibitor to tumor necrosis factor (TNF) blockers in rheumatoid arthritis (RA) patients ≥50 years old with at least one cardiovascular (CV) risk factor, a higher rate of all-cause mortality, including sudden cardiovascular death, was observed with the JAK inhibitor. Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with RINVOQ.

MALIGNANCIES

Lymphoma and other malignancies have been observed in patients treated with RINVOQ. In a large, randomized, postmarketing safety study comparing another JAK inhibitor with TNF blockers in RA patients, a higher rate of malignancies (excluding non-melanoma skin cancer [NMSC]), lymphomas, and lung cancer (in current or past smokers) was observed with the JAK inhibitor. 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, 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 cancers have been reported in patients treated with RINVOQ. 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 suncreen.

MAJOR ADVERSE CARDIOVASCULAR EVENTS

In a large, randomized, postmarketing study comparing another JAK inhibitor with TNF blockers in RA patients ≥50 years old with at least one CV risk factor, a higher rate of major adverse cardiovascular events (MACE) (defined as cardiovascular death, myocardial infarction, and stroke) was observed with the JAK inhibitor. Patients who are current or past smokers are at additional increased risk. Discontinue RINVOQ in patients that have experienced a myocardial infarction or stroke.

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.

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 a large, randomized, postmarketing study comparing another JAK inhibitor to TNF blockers in RA patients ≥50 years old with at least one CV risk factor, a higher rate of thrombosis was observed with the JAK inhibitor. Avoid RINVOQ in patients at risk. Patients with symptoms of thrombosis should discontinue RINVOQ and be promptly evaluated.

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.

GASTROINTESTINAL PERFORATIONS

Gastrointestinal perforations have been reported in clinical studies with RINVOQ. Monitor RINVOQ-treated patients who may be at risk for gastrointestinal perforation (e.g., patients with a history of diverticulitis or taking NSAIDs). Promptly evaluate patients presenting with new onset abdominal pain for early identification of GI perforation.

LABORATORY ABNORMALITIES

Neutropenia: Treatment with RINVOQ was associated with an increased incidence of neutropenia (absolute neutrophil count [ANC] <1000 cells/mm3).

Lymphopenia: Absolute lymphocyte counts (ALC) <500 cells/mm3 were reported in RINVOQ clinical studies.

Anemia: Decreases in hemoglobin levels to <8 g/dL were reported in RINVOQ clinical studies.

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.

Liver enzyme elevations: Treatment with RINVOQ was associated with increased incidence of liver enzyme elevation compared to placebo.

EMBRYO-FETAL TOXICITY

Based on findings in animal studies, RINVOQ may cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with RINVOQ and for 4 weeks after the final dose. Verify pregnancy status of females of reproductive potential prior to starting treatment with RINVOQ.

VACCINATION

Avoid use of live vaccines during, or immediately prior to, RINVOQ therapy. Prior to initiating RINVOQ, patients should be brought up to date on all immunizations, including varicella zoster or prophylactic herpes zoster vaccinations, in agreement with current immunization guidelines.

CONSISTENT
SAFETY PROFILE
ACROSS RA, PsA and AS2-4,7,16

Safety data from clinical trials across indications2-4,7,16

Consistent safety profile across RA, PsA, and AS2-4,7,16

Overall, the safety profile observed
in patients with active AS is consistent with
the safety profile observed in patients with rheumatoid arthritis and psoriatic arthritis.1

Long Term Safety data in RA, PsA, and AS

In RA studies, patients could advance or switch to RINVOQ from placebo, or be rescued to RINVOQ from active comparator or placebo as early as Week 12 depending on the study design.1

In PsA studies, all remaining placebo patients were switched to RINVOQ 15 mg QD or upadacitinib 30 mg QD (1:1 ratio) at Week 24.1

In the SELECT-AXIS 1 study, all patients randomized to placebo were switched to RINVOQ 15 mg QD at Week 14.1

RINVOQ 15 mg is the only approved dose in RA, PsA, and AS.1

Adverse reaction rates observed in clinical trials and LTE studies may not predict rates observed in clinical practice.

ADVERSE REACTIONS: The most common adverse reactions in RINVOQ RA, PsA, and AS clinical trials (≥1%) were: upper respiratory tract infection, herpes zoster, herpes simplex, bronchitis, nausea, cough, pyrexia, acne, and headache.1

TEAEs were defined as AEs with an onset date that is on or after the first dose of study drug, and no more than 30 days after the last dose of RINVOQ and placebo if subject discontinued study drug prematurely.4

*Included RINVOQ monotherapy and combination therapy with csDMARDs across 6 trials.
†Included RINVOQ monotherapy and combination therapy with DMARDs across 2 trials.
‡Included RINVOQ in 1 Phase 2/3 trial.

Well-studied
Safety Profile

Most Common Adverse Reactions from RINVOQ clinical trials

ANKYLOSING SPONDYLITIS6,17

Most Common Adverse Reactions from SELECT-AXIS 2 (14 Weeks)

Adverse reactions reported in >2% of ankylosing spondylitis patients treated with
RINVOQ 15 mg from the placebo-controlled study.

Common adverse events

Infections

  • In the placebo-controlled study SELECT-AXIS 2 through 14 weeks, infections were reported in 13% of patients treated with placebo and 15% of patients treated with RINVOQ 15 mg.6

ADVERSE REACTIONS: The most common adverse reactions in RINVOQ clinical trials (≥1%) were: upper respiratory tract infection, herpes zoster, herpes simplex, bronchitis, nausea, cough, pyrexia, acne, and headache.1

PSORIATIC ARTHRITIS18

Most Common Adverse Reactions from SELECT‑PsA 1 and SELECT‑PsA 2 (24 Weeks)

Adverse reactions reported in >1% of psoriatic arthritis patients treated with
RINVOQ 15 mg pooled from the placebo‑controlled studies.

Common adverse events

Infections

  • In the placebo-controlled studies SELECT-PsA 1 and SELECT-PsA 2 through 24 weeks, infections were reported in 33.5% of patients treated with placebo and 37.5% of patients treated with RINVOQ 15 mg.19

ADVERSE REACTIONS: The most common adverse reactions in RINVOQ clinical trials (≥1%) were: upper respiratory tract infection, herpes zoster, herpes simplex, bronchitis, nausea, cough, pyrexia, acne, and headache.1

RHEUMATOID ARTHRITIS1

Most Common Adverse Reactions from SELECT-COMPARE,
SELECT-NEXT, and
SELECT-BEYOND (12 Weeks)1

Adverse reactions reported in ≥1% of moderate to severe rheumatoid arthritis
patients treated with RINVOQ 15 mg pooled from the placebo‑controlled studies.

Common adverse events

Infections

  • In the placebo-controlled studies SELECT-COMPARE, SELECT-NEXT, and SELECT-BEYOND through 12/14 weeks, infections were reported in 20.9% of patients treated with placebo and 27.4% of patients treated with RINVOQ 15 mg.20
  • In the 12-month exposure dataset, the incident rate of infection was 83.8 per 100 patient years for patients treated with RINVOQ 15 mg.20

ADVERSE REACTIONS: The most common adverse reactions in RINVOQ clinical trials (≥1%) were: upper respiratory tract infection, herpes zoster, herpes simplex, bronchitis, nausea, cough, pyrexia, acne, and headache.1

LAB monitoring and
treatment considerations1

RINVOQ Lab Monitoring

Treatment with RINVOQ should not be initiated, or should be interrupted if:

Absolute neutrophil count
<1000 cells/mm3*

Absolute lymphocyte count
<500 cells/mm3*

Hemoglobin levels
<8 g/dL*

Liver enzyme elevations
and a
drug-induced liver
injury is suspected*

Patient has or develops a serious
or opportunistic infection*

  • RINVOQ initiation is not recommended in patients with active hepatitis B or hepatitis C.
  • RINVOQ is not recommended for use in patients with severe hepatic impairment.
  • RINVOQ has not been studied in patients with end-stage renal disease.
  • Discontinue RINVOQ in patients that have experienced a myocardial infarction
    or stroke.
  • Avoid RINVOQ in patients that may be at increased risk for thrombosis. Discontinue RINVOQ and promptly evaluate patients with symptoms of thrombosis.

*Treatment can be initiated or restarted after levels return above specified values, drug-induced liver injury diagnosis is excluded, or infection is controlled.

No dose adjustment is required for mild,
moderate, or severe renal impairment.1

No dose adjustment is required for mild or moderate hepatic impairment.1

Serious Infections:1 Closely monitor patients for the development of signs and symptoms of infection during and after treatment with RINVOQ.

Tuberculosis (TB):1 Test patients for latent and active TB prior to initiation. If positive, treat prior to 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:1 Screening and monitoring for viral hepatitis and herpes zoster reactivation should be performed in accordance with clinical guidelines before starting and during therapy with RINVOQ. If a patient develops herpes zoster, consider temporarily interrupting RINVOQ until the episode resolves.

HYPERSENSITIVITY:RINVOQ is contraindicated in patients with known hypersensitivity to upadacitinib or any of its excipients. If a clinically significant hypersensitivity reaction occurs, discontinue RINVOQ and institute appropriate therapy.

Embryo-Fetal Toxicity:1 Based on animal studies, RINVOQ may cause fetal harm when administered to pregnant women. Verify pregnancy status prior to starting treatment. Advise women to use effective contraception during and for 4 weeks after completion of treatment.

VACCINATIONS:1 Update immunizations, including varicella zoster or prophylactic herpes zoster, according to current immunization guidelines prior to initation. Avoid use of live vaccines during, or immediately prior to, RINVOQ therapy.

Lab Abnormalities from the Package Insert1

Neutropenia: Decreases in absolute neutrophil count (<1000 cells/mm3) was associated with RINVOQ treatment.

Lymphopenia: Decreases in lymphocyte count (<500 cells/mm3) were reported with RINVOQ treatment.

Anemia: Hemoglobin decreases below 8 g/dL were reported with RINVOQ treatment.

Lipid Elevations: Increases in lipid parameters including total cholesterol, triglycerides, LDL, and HDL were observed in patients treated with RINVOQ. Elevations in LDL and HDL cholesterol peaked by Week 8 and remained stable thereafter.

Liver Enzyme Elevations: Increased incidence in liver enzyme elevations was associated with RINVOQ compared to placebo.

RINVOQ® COMPLETE

Discover how RINVOQ Complete can provide
exceptional access and product support