For moderate to severe rheumatoid arthritis (RA) in adult TNFi-IR patients1

Safety data
FROM 6 ROBUST PHASE 3 TRIALS2,a

~4400
patients evaluated on upadacitinibb

>7000
patient-years exposure to
RINVOQ 15 mg
as of 6/30/20

~4.5 years
maximum in RA and
~2.6 years median long-term
exposure to RINVOQ 15 mg as of 6/30/20

Clinical Trial Overview

SELECT‑EARLY (Study RA‑I) Study Design Intro:1,3
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:1,4
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:1,5
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:1,6
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 bDMARDs. 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:1,7
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 protocol occurred at weeks 14, 18, 22, or 26.

SELECT-CHOICE Study Design Intro:8
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 IV at 0, 2, and 4 weeks, and every 4 weeks thereafter (n=309). The primary endpoint was ΔDAS28 CRP (noninferiority) at Week 12.

Well-studied
  safety profile1

Data from 5 robust Phase 3 clinical trials

Adverse Events of Special Interest1,9

Short-term safety data Short-term safety data Short-term safety data

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

TEAE=treatment emergent adverse event is defined as any adverse event with an onset date on or after the first dose of study drug and no more than 30 days after the last dose of study drug if subject discontinued study drug prematurely.9

SAFETY CONSIDERATIONS

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

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.

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.

GASTROINTESTINAL PERFORATIONS

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

Use of live, attenuated vaccines during, or immediately prior to, RINVOQ therapy is not recommended. Prior to initiating RINVOQ, patients should be brought up to date with all immunizations, including prophylactic zoster vaccinations, in agreement with current immunization guidelines.

consistent SAFETY PROFILE OF AEs
OBSERVED IN LONG-TERM ANALYSIS2

RINVOQ 15 mg median long-term exposure is ~2.6 years

Adverse Events of Special Interest2

Data as of June 30, 2020

Phase 3 Program AEs

Maximum exposure: ~4.5 years
Median exposure: ~2.6 years
>7,000 patient-years

Now with up to ~4.5 years of long‑term exposure2

Previously up to ~3.5 years of long-term exposure14

Adverse Events of Special Interest Adverse Events of Special Interest Adverse Events of Special Interest

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

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

*Included RINVOQ monotherapy and combination therapy with csDMARDs across 6 trials.

Infections were identified by the investigator as serious if they met one or more of the following seriousness criteria; death, life-threatening, hospitalization (initial or prolonged), disability or permanent damage, congenital anomaly/birth defect, required intervention to prevent permanent impairment or damage, or other serious important medical events.15

TEAE=treatment-emergent adverse event, defined as an adverse event with an onset date on or after the first dose of oral study drug and up to 30 days after last dose of RINVOQ.16

Well-studied
  safety profile1

Common Adverse Reactions

Common adverse events Common adverse events Common adverse events

Infections

  • In the placebo‑controlled studies 
    SELECT-BEYOND, SELECT-NEXT, and
    SELECT-COMPARE through 12/14 weeks, infections were reported in 20.9% of patients treated with placebo and 27.4% in patients treated with RINVOQ 15 mg.17
  • In the 12 month pooled safety datac, the incidence rate of infection was 83.8* per 100 patient-years for patients treated with RINVOQ 15 mg.1,17

aPatients were on background MTX or csDMARDS.
bURTI includes: acute sinusitis, laryngitis, nasopharyngitis, oropharyngeal pain, pharyngitis, pharyngotonsillitis, rhinitis, sinusitis, tonsillitis, viral upper respiratory tract infection.
cSELECT-EARLY, SELECT-MONOTHERAPY, SELECT-NEXT, and SELECT-BEYOND.
*615/733.6 (n/PYS)

Lab Monitoring and treatment
considerations1

Lab monitoring Lab monitoring Lab monitoring

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

Absolute lymphocyte count <500 cells/mm3*; Absolute neutrophil count <1000 cells/mm3*; Hemoglobin levels <8 g/dL*; Elevated hepatic transaminases and drug-induced liver injury is suspected; Patient develops a serious infection* Absolute lymphocyte count <500 cells/mm3*; Absolute neutrophil count <1000 cells/mm3*; Hemoglobin levels <8 g/dL*; Elevated hepatic transaminases and drug-induced liver injury is suspected; Patient develops a serious infection* Absolute lymphocyte count <500 cells/mm3*; Absolute neutrophil count <1000 cells/mm3*; Hemoglobin levels <8 g/dL*; Elevated hepatic transaminases and drug-induced liver injury is suspected; Patient develops a serious infection*

*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

Rinvoq has not been studied in subjects with end stage renal disease.1

RINVOQ is not recommended for use in patients with severe 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 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 for viral hepatitis and monitoring for reactivation should be performed in accordance with clinical guidelines before starting and during therapy with RINVOQ.

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.

Lab abnormalitiesfrom the Controlled Period
of the Phase 3 program
(Week 12 or 14)1

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

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

Anemia: Hemoglobin decreases below 8 g/dL in at least one measurement occurred in <0.1% of patients treated with RINVOQ 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 >5x ULN were transient and did not require treatment discontinuation.

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