THE ONLY AD THERAPY WITH
SUPERIORITY DATA IN
HEAD-TO-HEAD
MONOTHERAPY TRIAL VS
DUPIXENT® (dupilumab)2

LEVEL UP Overview

Pivotal Trial Endpoints in MEASURE UP 1 and MEASURE UP 21,3

Double-blind, placebo-controlled; NRI-C; ITT

WP-NRS ≥4 improvement at Week 16

Ranked secondary endpoint

MEASURE UP 1:
RINVOQ 15 mg 52%* (n=274)
RINVOQ 30 mg 60%* (n=280)
Placebo 12% (n=272)

MEASURE UP 2:
RINVOQ 15 mg 42%* (n=270)
RINVOQ 30 mg 60%* (n=280)
Placebo 9% (n=274)

EASI 75 at Week 16

Co-primary endpoint

MEASURE UP 1:
RINVOQ 15 mg 70%* (n=281)
RINVOQ 30 mg 80%* (n=285)
Placebo 16% (n=281)

MEASURE UP 2:
RINVOQ 15 mg 60%* (n=276)
RINVOQ 30 mg 73%* (n=282)
Placebo 13% (n=278)

vIGA 0/1 at Week 16

Co-primary endpoint

MEASURE UP 1:
RINVOQ 15 mg 48%* (n=281)
RINVOQ 30 mg 62%* (n=285)
Placebo 8% (n=281)

MEASURE UP 2:
RINVOQ 15 mg 39%* (n=276)
RINVOQ 30 mg 52%* (n=282)
Placebo 5% (n=278)

*p≤0.001; RINVOQ vs placebo.

RECOMMENDED DOSAGE IN AD1:

  • 30 mg is not an approved starting dose
  • For pediatric patients ≥12 years (40+ kg) and adults <65 years old: Initiate with 15 mg once daily. If an adequate response is not achieved, consider increasing dosage to 30 mg once daily. Discontinue if an adequate response is not achieved with 30 mg dose. Use the lowest effective dose needed to maintain response
  • For 65+ years: Recommended dosage is 15 mg once daily
See MEASURE UP 1 and 2 Study Details

Please see Important Safety Information, including BOXED WARNING on Serious Infections, Mortality, Malignancies, Major Adverse Cardiovascular Events, and Thrombosis, below.

Learn more about these and the full Important Safety Information below 

LEVEL UP Clinical Trial1,2,4

LEVEL UP: A prospective, open-label, assessor-blinded study in RINVOQ's indicated population with the approved starting dose

Phase 3b/4, 2-part, head-to-head, multicenter, randomized, open-label, efficacy–assessor-blinded study that evaluated the safety and efficacy of upadacitinib vs dupilumab in moderate to severe atopic dermatitis (AD) patients not adequately controlled with systemic therapy or when use of those therapies are inadvisable. Upadacitinib was dosed as 15 mg once daily starting dose and dose-adjusted to 30 mg based on clinical response per protocol starting at Week 4 versus dupilumab, per its labeled dose.

Clinical decisions regarding treatment selection should take into account all relevant information, including full benefit-risk profiles in each product’s full Prescribing Information.
 

is indicated for 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.

Boxed Warning on serious infections, mortality, malignancies, major adverse cardiovascular events, and thrombosis

DUPIXENT® (dupilumab).

is indicated for patients 6+ months of age with moderate to severe AD not adequately controlled with topical prescription therapies.

No Boxed Warning

These are not all the risks associated with RINVOQ and DUPIXENT. Please see additional Important Safety Information by clicking the Label Highlights here.

Conclusions comparing the overall benefit-risk profile of 2 active therapies cannot be made on a single clinical trial alone.

Study Details

†DUPIXENT is a registered trademark of Sanofi Biotechnology. See US Prescribing Information for more information.

Significantly More RINVOQ Patients Achieved Higher-Level Disease Control‡ vs DUPIXENT at Week 162,5

HIGHER-LEVEL
DISEASE CONTROL‡ in both itch & skin

 

 ‡Defined by simultaneous achievement of WP-NRS 0/1 & EASI 90; higher than WP-NRS ≥4 improvement and EASI 75. Itch & skin are clinical features of AD; other outcome measures may exist.

While most studies focus on adequate control over itch and skin in AD, AbbVie is the first company to combine WP-NRS 0/1 and EASI 90 data as a primary endpoint—elevating what control could mean for AD.1,2,4,6,7‡

 

Label Highlights for RINVOQ and DUPIXENT
Monotherapy Superiority Data

Proportion of patients achieving itch and skin improvement

RINVOQ vs DUPIXENT at Week 162,5

LEVEL UP Head-to-Head Data.

*RINVOQ was dosed as 15 mg once daily starting and dose-adjusted to 30 mg based on clinical response per protocol starting at Week 4 versus DUPIXENT, per its labeled dose. The study was powered to evaluate all RINVOQ vs all DUPIXENT-treated patients without regard to dose.

†Defined by simultaneous achievement of WP-NRS 0/1 & EASI 90; higher than WP-NRS >4 improvement and EASI 75. Itch & skin are clinical features of AD; other outcome measures may exist.

‡p<0.0001; NRI-MI, ITT.

§n-value includes patients whose baseline WP-NRS is >1.

DATA LIMITATIONS:

Due to the open-label study design, patients knew the drug they were taking, which may have introduced bias.

LEVEL UP is an open-label, phase 3b/4, multicenter, randomized, 2-part, head-to-head, efficacy–assessor-blinded study that evaluated the safety and assessor-blinded efficacy of upadacitinib vs dupilumab in moderate to severe atopic dermatitis patients not adequately controlled with systemic therapy or when use of those therapies are inadvisable.2

 

DATA LIMITATIONS:

Due to the open-label study design, patients knew the drug they were taking, which may have introduced bias.

RINVOQ and DUPIXENT have different indications as well as Warnings and Precautions (including BOXED WARNING for RINVOQ). Please refer to Label Highlights for differences in Safety Profiles.

WP-NRS 0/1 improvement at Week 22,5

Ranked secondary endpoint

8%‡ RINVOQ

1% DUPIXENT

EASI 90 responses as early as Week 42,5

Ranked secondary endpoint

24%‡ RINVOQ

10% DUPIXENT

‡p<0.0001; NRI-MI, ITT.

Study Details
See Efficacy Data from Pivotal Trials

Safety Considerations

Serious Infections: RINVOQ-treated patients are at increased risk of serious bacterial (including tuberculosis [TB]), fungal, viral, and opportunistic infections leading to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants, such as methotrexate or corticosteroids.

Mortality: A higher rate of all-cause mortality, including sudden cardiovascular (CV) death, was observed with a Janus kinase inhibitor (JAKi) in a study comparing another JAKi with tumor necrosis factor (TNF) blockers in rheumatoid arthritis (RA) patients ≥50 years with ≥1 CV risk factor.

Malignancies: Malignancies have occurred in RINVOQ-treated patients. A higher rate of lymphomas and lung cancer (in current or past smokers) was observed with another JAKi when compared with TNF blockers in RA patients.

Major Adverse Cardiovascular Events: A higher rate of CV death, myocardial infarction, and stroke was observed with a JAKi in a study comparing another JAKi with TNF blockers in RA patients ≥50 years with ≥1 CV risk factor. History of smoking increases risk.

Thrombosis: Deep venous thrombosis, pulmonary embolism, and arterial thrombosis have occurred in patients treated with JAK inhibitors used to treat inflammatory conditions. A higher rate of thrombosis was observed with another JAKi when compared with TNF blockers in RA patients.

Hypersensitivity: RINVOQ is contraindicated in patients with hypersensitivity to RINVOQ or its excipients.

Other Serious Adverse Reactions: Hypersensitivity Reactions, Gastrointestinal Perforations, Laboratory Abnormalities, and Embryo-Fetal Toxicity.

Learn more about these and the full Important Safety Information below 

Adverse Events (AEs) of Special Interest at Week 16
Across Multiple RINVOQ AD Studies8-10

AEs of special interest were generally consistent across multiple RINVOQ AD studies

<<Swipe table to see more

    All Subjects
MEASURE UP 1, 2, AD UP,
and Phase 2b		   All Subjects
LEVEL UP Period 1
    Placebo (N=902) (PY=255.0) % (n/100 PY)   RINVOQ 15 mg (N=899) (PY=271.2) % (n/100 PY)   RINVOQ 30 mg (N=906) (PY=273.3) % (n/100PY)   RINVOQa (N=458) (PY=137.3) % (n/100 PY)   DUPIXENTa (N=461) (PY=139.4) % (n/100 PY)
INFECTIONS                    
Any serious infection   0.6 (2.0)   0.8 (2.6)   0.4 (1.5)   0   0.2 (0.7)
Active TB   0   0   0   0   0
Opportunistic infection
(excluding TB and herpes zoster)b		   0.4 (1.6)   0.7 (2.2)   0.8 (2.6)   1.1 (3.7)   0
Herpes zoster   0.6 (2.0)   1.6 (5.2)   1.5 (5.2)   1.7 (5.9)   0.4 (1.4)
MORTALITY                    
Mortality   0   0   0   0   0
MALIGNANCY                    
Malignancy (excluding NMSC)c   0   0   0.4 (1.5)   0   0
NMSCc   0   0.3 (1.1)   0.2 (0.7)   0   0
CARDIOVASCULAR EVENTS                  
Adjudicated MACEc   0   0   0   0   0
Adjudicated VTEc   0.1 (0.4)   0   0   0   0
GASTROENTEROLOGICAL EVENTS                
Adjudicated GI perforationsc   0   0   0   0   0

LEVEL UP was not designed or statistically powered to evaluate safety outcomes, including between RINVOQ and DUPIXENT nor to detect the risks revealed by the larger and longer XELJANZ ORAL Surveillance post-marketing study.

RINVOQ has a BOXED WARNING which includes Serious Infections, Mortality, Malignancies, Major Adverse Cardiovascular Events, and Thrombosis.

Safety rates in the LEVEL UP study were generally consistent with the known profile of RINVOQ for atopic dermatitis.


aRINVOQ was dosed as 15 mg once daily starting and dose-adjusted to 30 mg based on clinical response per protocol starting at Week 4 versus DUPIXENT, per its labeled dose. The study was powered to evaluate all RINVOQ versus all DUPIXENT-treated patients without regard to dose.

See full Prescribing Information for DUPIXENT, which reflects different rates of AEs from those observed in the LEVEL UP clinical trial.4

bAll events were eczema herpeticum.

cPer protocol, patients experiencing AEs of malignancy (except for localized NMSC or cancer of the cervix in situ), adjudicated GI perforations, and adjudicated VTE were required to discontinue therapy.

AEs of special interest: 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 upadacitinib and placebo.

MACE=major adverse cardiovascular event; n/100 PY=number of subjects with at least 1 event per 100 PY; NMSC=nonmelanoma skin cancer; PY=patient-years; TB=tuberculosis; VTE=venous thromboembolism.

Study Details
See Long-Term Safety Data from Pivotal Trials

Highlights of Prescribing Information for RINVOQ and DUPIXENT1,4

<<Swipe table to see more

  RINVOQ® (upadacitinib)   DUPIXENT® (dupilumab)
Indication and Usage 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.   Adult and pediatric patients aged 6 months and older with moderate-to-severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. DUPIXENT can be used with or without topical corticosteroids.
Limitations of Use RINVOQ is not recommended for use in combination with other JAK inhibitors, biologic immunomodulators, or with other immunosuppressants.   None
Boxed Warnings
  • Increased risk of serious bacterial, fungal, viral, and opportunistic infections leading to hospitalization or death, including tuberculosis (TB). Interrupt treatment with RINVOQ if serious infection occurs until the infection is controlled. Test for latent TB before and during therapy; treat latent TB prior to use. Monitor all patients for active TB during treatment, even patients with initial negative, latent TB test.
  • Higher rate of all-cause mortality, including sudden cardiovascular death with another Janus kinase (JAK) inhibitor vs. tumor necrosis factor (TNF) blockers in rheumatoid arthritis (RA) patients.
  • Malignancies have occurred in patients treated with RINVOQ. Higher rate of lymphomas and lung cancers with another JAK inhibitor vs. TNF blockers in RA patients.
  • Higher rate of MACE (defined as cardiovascular death, myocardial infarction, and stroke) with another JAK inhibitor vs. TNF blockers in RA patients.
  • Thrombosis has occurred in patients treated with RINVOQ. Increased incidence of pulmonary embolism, venous and arterial thrombosis with another JAK inhibitor vs. TNF blockers.
   None
Contraindications Known hypersensitivity to upadacitinib or any of the excipients in RINVOQ   Known hypersensitivity to dupilumab or any excipients in DUPIXENT
Warnings and Precautions
  • Serious Infections: Avoid use in patients with active, serious infection, including localized infections.
  • Hypersensitivity: Serious hypersensitivity reactions (e.g., anaphylaxis) have been reported. Discontinue if a serious hypersensitivity reaction occurs.
  • Gastrointestinal (GI) Perforations: Monitor patients at risk for GI perforations and promptly evaluate patients with symptoms.
  • Laboratory Abnormalities: Monitoring recommended due to potential changes in lymphocytes, neutrophils, hemoglobin, liver enzymes and lipids.
  • Embryo-Fetal Toxicity: May cause fetal harm based on animal studies. Advise female patients of reproductive potential of the potential risk to a fetus and to use effective contraception.
  • Vaccinations: Avoid use with live vaccines.
  • Medication Residue in Stool: Observed in stool or ostomy output in patients with shortened GI transit times. Monitor patients clinically and consider alternative treatment if inadequate therapeutic response.
  
  • Hypersensitivity: Hypersensitivity reactions including anaphylaxis, serum sickness, angioedema, urticaria, rash, erythema nodosum, and erythema multiforme have occurred. Discontinue DUPIXENT in the event of a hypersensitivity reaction.
  • Conjunctivitis and Keratitis: Advise patients to report new onset or worsening eye symptoms to their healthcare provider. Consider ophthalmological examination, as appropriate.
  • Eosinophilic Conditions: Be alert to vasculitic rash, worsening pulmonary symptoms, and/or neuropathy, especially upon reduction of oral corticosteroids.
  • Reduction of Corticosteroid Dosage: Do not discontinue systemic, topical, or inhaled corticosteroids abruptly upon initiation of DUPIXENT. Decrease steroids gradually, if appropriate.
  • Arthralgia: Advise patients to report new onset or worsening joint symptoms to their healthcare provider. If symptoms persist or worsen, consider rheumatological evaluation and/or discontinuation of DUPIXENT.
  • Parasitic (Helminth) Infections: Treat pre-existing helminth infections before initiating DUPIXENT. If patients become infected while receiving DUPIXENT and do not respond to anti-helminth treatment, discontinue DUPIXENT until the infection resolves.
  • Vaccinations: Avoid use of live vaccines.
Adverse Reactions

Atopic Dermatitis: Adverse reactions (≥1%) are: upper respiratory tract infections, acne, herpes simplex, headache, blood creatine phosphokinase increased, cough, hypersensitivity, folliculitis, nausea, abdominal pain, pyrexia, increased weight, herpes zoster, influenza, fatigue, neutropenia, myalgia, and influenza like illness.

  

Atopic Dermatitis (incidence ≥1%): Injection site reactions, conjunctivitis, blepharitis, oral herpes, keratitis, eye pruritus, other herpes simplex virus infection, dry eye, and eosinophilia.
Drug Interactions
  • Strong CYP3A4 Inhibitors: See the Full Prescribing Information for dosage modification for patients with atopic dermatitis, ulcerative colitis, and Crohn’s disease.
  • Strong CYP3A4 Inducers: Coadministration of RINVOQ with strong CYP3A4 inducers is not recommended.
   None
Use in Specific Populations
  • Lactation: Advise not to breastfeed.
  • Hepatic Impairment: RINVOQ is not recommended in patients with severe hepatic impairment.
   None

Please see additional Important Safety Information for RINVOQ.

Please see Full Prescribing Information for RINVOQ.

LEVEL UP your conversation

Talk to your patients about the LEVEL UP head-to-head data for both itch & skin.