Safety Profile in Psoriatic Arthritis | RINVOQ® (upadacitinib)

For active psoriatic arthritis (PsA) in adult TNFi‑IR patients¹

SAFETY DATA
18 CLINICAL TRIALS
ACROSS 5 INDICATIONS^1-6,*
RA, PSA, AS, AD & UC

>10,500
patients in global clinical
trials across US-approved
indications, including pediatrics
12+ years in AD^1-4,6,†

>18,500
patient-years of exposure
to RINVOQ 15 or 30 mg^3,6-10,‡

~5.5 years
max exposure beginning in RA
(~3.5 yrs median) to RINVOQ 15 mg
as of 6/30/21^7,11,§

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

*Includes 2 PsA phase 3 studies (SELECT‑PsA 1 and SELECT‑PsA 2); 6 RA phase 3 studies (SELECT‑EARLY, SELECT‑MONOTHERAPY, SELECT‑NEXT, SELECT‑COMPARE, SELECT‑BEYOND, and SELECT‑CHOICE); 1 AS phase 2/3 study (SELECT‑AXIS 1) and 1 AS phase 3 study (SELECT‑AXIS 2); 4 AD phase 3 studies (MEASURE UP 1, MEASURE UP 2, AD UP, and HEADS UP); and 4 UC phase 3 studies (U‑ACHIEVE Induction, U‑ACCOMPLISH Induction, U‑ACHIEVE Maintenance, and the long‑term extension study).^1‑6

†PsA: RINVOQ 15 mg, upadacitinib 30 mg; RA: RINVOQ 15 mg, upadacitinib 30 mg; AS: RINVOQ 15 mg; AD: RINVOQ 15 mg and RINVOQ 30 mg; UC: RINVOQ 15 mg, 30 mg, and 45 mg. RINVOQ 15 mg is the approved dose in PsA, RA, and AS; RINVOQ 15 mg and 30 mg are the approved doses in AD; RINVOQ 15 mg, 30 mg and 45 mg are the approved doses in UC.^1‑4,6,9

‡Includes 2504.6 patient‑years in PsA trials as of 06/2020, 12,259.5 patient‑years in RA trials as of 06/2021, 577.3 patient‑years in AS trials as of 11/2020 for SELECT‑AXIS 1 and 08/2021 for
SELECT‑AXIS 2 study 1, 2787.6 patient‑years in AD trials as of 11/2020, and 381.1 patient‑years in UC trials as of 04/2021.^3,6-10,12

^§In PsA: ~3 years maximum exposure (~1.3 years median) to RINVOQ 15 mg as of 06/2020; In AS: ~2.3 years max. exposure (~1.7 yrs median) to RINVOQ 15 mg as of 6/2020.^3,13

AD=atopic dermatitis; AS=ankylosing spondylitis; IR=intolerance or inadequate response; PsA=psoriatic arthritis; RA=rheumatoid arthritis; TNFi=tumor necrosis factor inhibitor; UC=ulcerative colitis

WELL-STUDIED
Safety Profile in PsA¹
Safety data at Week 24

Adverse events of special interest^12,14

Adverse reaction rates observed in clinical trials may not fully characterize the risks of RINVOQ. Certain adverse events may require longer observation periods and longer-term patient exposure to ascertain risk.

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.¹⁴

SAFETY CONSIDERATIONS

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

WARNINGS & PRECAUTIONS

Well-studied
Safety Data Across
5 Indications^{1,3,7,9‑12,15}

AbbVie is conducting the 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.

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

In PsA studies: Includes 2 Phase 3 trials as of 06/2020.
In RA studies: Includes 6 Phase 3 trials as of 06/2021.
In AS studies: Includes 1 Phase 2/3 trial as of 11/2020 for SELECT-AXIS 1.
In AD studies: Includes safety data from 3 Phase 3 trials including adults and
adolescents as of 11/2020.
In UC studies: Includes 1 Phase 3 trial as of 04/2021. Includes those who responded
to 45 mg induction dose to RINVOQ at Week 8.

Overall, the safety profile observed in patients with active PsA treated with RINVOQ 15 mg is consistent with the safety profile observed in patients with RA, with the addition of herpes zoster, herpes simplex, acne, and bronchitis.

TEAE=treatment emergent adverse event, defined as an adverse event with onset on or after first dose of study drug and up to 30 days after last dose of RINVOQ.¹⁴

Well-studied
safety profile

Most Common Adverse Reactions from RINVOQ Clinical Trials

PsA

PSORIATIC ARTHRITIS¹⁴

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.

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.¹⁶

ADVERSE REACTIONS: The most common adverse reactions in RINVOQ clinical trials were upper respiratory tract infections, herpes zoster, herpes simplex, bronchitis, nausea, cough, pyrexia, acne, headache, increased blood creatine phosphokinase, hypersensitivity, folliculitis, abdominal pain, increased weight, influenza, fatigue, neutropenia, myalgia, influenza-like illness, elevated liver enzymes, and rash.¹

Inform patients that retinal detachment has been reported in clinical trials with RINVOQ. Advise patients to immediately inform their healthcare provider if they develop any sudden changes in vision while receiving RINVOQ.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.

Infections

In the placebo-controlled study 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.¹⁷
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.¹⁷

Lab Monitoring and treatment
considerations¹

Lab Monitoring

Lab Abnormalities

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 patients with severe hepatic impairement.
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:¹ 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 initiation. Avoid use of live vaccines during, or immediately prior to, RINVOQ therapy.

Lab Abnormalities from the Placebo‑Controlled Period of the PsA^a and RA^b Programs^1,16,c

Neutropenia: Decreases in absolute neutrophil count (<1000 cells/mm³) occurred in 0.9% of patients treated with RINVOQ in PsA and 1.1% of patients treated with RINVOQ in RA in the first 3 months of exposure.

Lymphopenia: Decreases in lymphocyte counts (<500 cells/mm³) occurred in 1.3% of patients treated with RINVOQ in PsA and 0.9% of patients treated with RINVOQ in RA in the first 3 months of exposure.

Anemia: Hemoglobin decreases below 8 g/dL in at least one measurement occurred in 1.1% of patients treated with RINVOQ in PsA and <0.1% of patients treated with RINVOQ in RA in the first 3 months of exposure.

Lipid Elevations: Increases in lipid parameters including total cholesterol, triglycerides, low‑density lipoproteins (LDL), and high‑density lipoproteins (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: Increases in liver enzyme levels >3 times the upper limit of normal (ULN) were observed in patients treated with RINVOQ.

Creatine Phosphokinase Elevations: Increases in creatine phosphokinase (CPK) levels >5 times the upper limit of normal were observed in patients treated with RINVOQ. Most elevations >5 times ULN were transient and did not require treatment discontinuation.