*

48

17

*

31

10

Study design overview1,2

Clinical summary: SELECT-NEXT

Screening period 12-week, randomised, double-blind treatment period Blinded extension (up to 5 years)

This is a promotional material organised and funded by AbbVie Ltd, for UK healthcare professionals only.February 2021 | UK-UPAD-210044

Significantly more patients achieved low disease activity and remission with RINVOQ + csDMARD(s) vs PBO + csDMARD(s), as early as Week 1 and sustained through Week 122

Pat

ient

s, %

Mea

n ch

ange

in D

AS

28

-CR

P

Time, weeksWeek 12

0

20

-2.0

10

-2.5

40

-1.030

-1.5

60

0.00

50

-0.5

*p≤0.0001 RINVOQ + csDMARD(s) vs PBO + csDMARD(s); Inominal p≤0.0001 RINVOQ + csDMARD(s) vs PBO + csDMARD(s).

Adapted from Burmester GR, et al. Lancet. 2018;391:2503–12.

Study findings at-a-glanceThe analysis in this study was performed using non-responder imputation.

Onset of action was

rapid for RINVOQ 15 mg OD + csDMARD(s) vs PBO + csDMARD(s),

with a significant decrease from baseline in DAS28-CRP

as early as Week 1 and continuing through

Week 12.2

Significantly more patients

treated with RINVOQ + csDMARD(s) achieved DAS28-CRP ≤3.2 (LDA)

vs PBO + csDMARD(s) at Week 12, reaching its primary endpoint.1,2

At Week 12, significant

improvements in physical function and

health-related quality of life measures were observed

for RINVOQ 15 mg OD + csDMARD(s) vs PBO

+ csDMARD(s).2

A Phase III study comparing RINVOQ to PBO treatment in

patients with rheumatoid arthritis, who have had an

inadequate response to csDMARD(s).1,2

The study findings show that RINVOQ

15 mg OD + csDMARD(s) achieves better remission

and clinical responses than PBO + csDMARD(s).2

Adults with moderate- to-severe

RA and inadequate response to csDMARD(s) Ra

ndom

isat

ion

2:2:

1:1

Baseline W 12

†Upadacitinib 30 mg OD is an unlicensed dose and therefore, only the RINVOQ 15 mg OD results will be presented in this summary.3

PBO (n=221)

RINVOQ 15 mg OD (n=221)

All participants on background csDMARD(s)

Upadacitinib 30 mg OD (n=219)†

Upadacitinib 30 mg OD†

RINVOQ 15 mg OD

DAS28-CRP <2.6 (REMISSION)

The safety profile of RINVOQ was

consistent with other Phase III SELECT

studies – COMPARE, MONOTHERAPY and BEYOND.2

DAS28-CRP ≤3.2 (LDA)

PBO + csDMARD(s) (n=221) RINVOQ 15 mg OD + csDMARD(s) (n=221)

121086421

-2.25*I

I

I

I-1.02

Primary endpoint at

Week 12: DAS28-CRP ≤3.2 for RINVOQ +

csDMARD(s) vs PBO + csDMARD(s)

6

36

15

64*

38I

21I

ACR50 ACR70

RINVOQ + csDMARD(s) was associated with improvements in clinical symptoms, physical function and quality of life vs PBO + csDMARD(s) alone at Week 122

Pat

ient

s, %

ACR200

30

10

221 207 207 221n= n= n= n=221 209 207 221221 221221 221

20

40

60

50

70

80

PBO + csDMARD(s) RINVOQ 15 mg OD + csDMARD(s)

3.0

7.6*

Cha

nge

from

bas

elin

e

SF-36 (PCS)

Week 12 Week 12

0

2

4

6

8

10

3.0

7.9*

FACIT-F

0

2

4

6

8

10

This is a promotional material organised and funded by AbbVie Ltd, for UK healthcare professionals only.February 2021 | UK-UPAD-210044

*p≤0.0001 RINVOQ + csDMARD(s) vs PBO + csDMARD(s); Inominal p≤0.0001 RINVOQ + csDMARD(s) vs PBO + csDMARD(s).

Adapted from Burmester GR, et al. Lancet. 2018;391:2503–12.

ACR20/50/70, American College of Rheumatology 20%/50%/70% improvement criteria; AE, adverse event; BL, baseline; csDMARD, conventional synthetic disease-modifying antirheumatic drug; DAS28-CRP, Disease Activity Score for 28 joint counts based on C-reactive protein; FACIT-F, Functional Assessment of Chronic Illness Therapy–Fatigue; HAQ-DI, Health Assessment Questionnaire Disability Index; LDA, low disease activity; MACE, major adverse cardiovascular event; OD, once daily; PBO, placebo; PCS, physical component summary; RA, rheumatoid arthritis; SF-36, Short-Form 36-item Health Survey; VTE, venous thromboembolic event.References: 1. ClinicalTrials.gov. NCT02675426. Available at: https://clinicaltrials.gov/ct2/show/NCT02675426. Accessed: February 2021; 2. Burmester GR, et al. Lancet. 2018;391:2503–12 and Supplementary data; 3. RINVOQ [Summary of Product Characteristics]. AbbVie Deutschland GmbH & Co. KG; Current SmPC.

RINVOQ 15 mg OD + csDMARD(s)

(n=221)

PBO + csDMARD(s) (n=221)

Serious AEs 4% 2%

Serious infections <1% <1%

Herpes zoster <1% <1%

Deaths 0 0

Adjudicated MACE 0 0

Adjudicated VTEs 0 0

Conclusions2Safety outcomes through Week 122

In patients with RA who had an inadequate response to csDMARD(s), significant improvements in clinical outcomes were observed as early as Week 1 when patients were treated with RINVOQ 15 mg OD + csDMARD(s) vs PBO + csDMARD(s).

All key secondary endpoints (change from BL in DAS28-CRP, SF-36, FACIT-F and HAQ-DI, DAS28-CRP <2.6 and ACR20 response) were achieved at Week 12 by patients receiving RINVOQ 15 mg OD + csDMARD(s).

Please refer to the Summary of Product Characteristics for full safety information.Adapted from Burmester GR, et al. Lancet. 2018;391:2503–12.

-0.26

Cha

nge

from

bas

elin

e

HAQ-DI

-1.0

-0.8

-0.6

-0.4

-0.2

0.0

*-0.61

Prescribing Information (PI)

RINVOQ® (upadacitinib) 15 mg prolonged-release tablets. Refer to Summary of Product Characteristics (SmPC) for full prescribing information.PRESENTATION: Each tablet contains upadacitinib hemihydrate, equivalent to 15mg upadacitinib. INDICATION: Treatment of moderate to severe active rheumatoid arthritis (RA) and active psoriatic arthritis (PsA) in adult patients who have responded inadequately to,or who are intolerant to one or more disease-modifying anti-rheumatic drugs (DMARDs). RINVOQ may be used as monotherapy or in combination with methotrexate. Treatment of active ankylosing spondylitis (AS) in adult patients who have responded inadequately to conventional therapy. DOSAGE AND ADMINISTRATION: Intended for use under guidance and supervision of a physician experienced in diagnosis and treatment of RA, PsA and AS. Dosage: The recommended oral dose is 15mg once daily. Consideration should be given to discontinuing treatment in patients with AS who have shown no clinical response after 16 weeks of treatment. Some patients with initial partial response may subsequently improve with continued treatment beyond 16 weeks. Special Populations: Elderly: No dose adjustment required for patients aged 65 years and older, limited data for patients aged 75 and older. Renal: No dose adjustment required in mild-moderate renal impairment, use with caution in patients with severe renal impairment. Upadacitinib has not been studied in subjects with end stage renal disease. Hepatic impairment: Should not be used in patients with severe Child Pugh C impairment. Paediatric Population: No data available. CONTRAINDICATIONS: Hypersensitivity to active substance or excipients. Active TB or active serious infections. Severe hepatic impairment. Pregnancy. SPECIAL WARNINGS AND PRECAUTIONS: See SmPC for full details.Immunosuppression: Combination use, with immunosuppressants e.g. azathioprine, ciclosporin, tacrolimus, and biologic DMARDs or other Janus kinase (JAK) inhibitors has not been evaluated in clinical studies and is not recommended as the risk of additive immunosuppression cannot be excluded. Serious infections: Serious and fatal infections have been reported. Caution when treating patients ≥65 years. Frequently reported –

pneumonia and cellulitis. Bacterial meningitis has been reported. Opportunistic infections reported - multidermatomal herpes zoster, oral/oesophageal candidiasis, and cryptococcosis. Do not initiate treatment in patients with active infection or underlying conditions that may predispose patients to infection. Consider the risk/benefit of treatment in patients with; chronic or recurrent infection, history of serious or opportunistic infection, those exposed to tuberculosis (TB), those who have resided or travelled in areas of endemic TB or endemic mycoses. Closely monitor patients and interrupt treatment if there are signs and symptoms of infection pre and post treatment. Tuberculosis: Pre-screen patients for active or latent TB. RINVOQ should not be given to patients with active TB. Consider anti-TB therapy in patients with previously untreated latent TB and consult with a physician with experience in TB therapy and whether initiating anti-TB therapy is appropriate for an individual patient. 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: Cases of herpes virus reactivation have been reported e.g., herpes zoster. If herpes zoster is reactivated, consider interruption of therapy until the episode resolves. Screen pre-therapy for viral hepatitis and monitor regularly for reactivation. Patients, positive for hepatitis C antibody/hepatitis C virus RNA and hepatitis B surface antigen/hepatitis B virus DNA were excluded from clinical studies. If hepatitis is detected while receiving therapy, a liver specialist should be consulted. Vaccination: Use of live, attenuated vaccines during or immediately prior to therapy is not recommended. It is recommended that patients be brought up to date with all immunisations, including prophylactic zoster vaccinations prior to starting therapy, in agreement with current immunisation guidelines. Malignancy: Immunomodulatory therapies may increase the risk of malignancies including lymphoma and non-melanoma skin cancer in RA patients. Malignancies were observed in clinical studies (see SmPC). Haematological abnormalities: Do not start therapy if Absolute Neutrophil Count <1,000 cells/mm3, Absolute Lymphocyte Count <500 cells/mm3 and Hb <8 g/dL. Monitor patients and temporarily stop therapy if abnormal haematological parameters as specified are detected during routine patient management. Cardiovascular Risk: RA patients have an increased risk for cardiovascular disorders. Manage patient’s risk factors for e.g. hypertension, hyperlipidaemia as per usual standard or care.Lipids: Monitor total cholesterol, LDL and HDL at 12 weeks and thereafter according to international guidelines. Elevated LDL in clinical trials decreased to pre-treatment levels

in response to statin therapy, although evidence is limited. The effect of these lipid parameter elevations on cardiovascular morbidity and mortality has not been determined. Hepatic transaminase elevations: Monitor 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. In such cases therapy should be interrupted until this diagnosis is excluded. Venous thromboembolism: Deep vein thrombosis (DVT) and pulmonary embolism (PE) have been reported in patients receiving JAKi. Use therapy with caution in patients at high risk for DVT/PE. Risk factors should be determined by patients age, obesity and medical history of DVT/PE, patients undergoing major surgery and prolonged immobilisation. If clinical features of DVT/PE occur discontinue therapy and evaluate promptly. ADVERSE REACTIONS: Refer to SmPC for full details on adverse reactions.Very common adverse reactions (≥1/10): Upper respiratory tract infections. Common adverse reactions (≥1/100 to <1/10): Bronchitis, Herpes zoster, Herpes simplex, Neutropaenia, hypercholesterolaemia, cough, nausea, acne, pyrexia, increased blood CPK/ALT/AST and increased weight. Serious adverse reactions: Please see above.LEGAL CLASSIFICATION: POMLOCAL REPPRESENTATIVE: AbbVie Ltd, Maidenhead, SL6 4UB, UKMARKETING AUTHORISATION NUMBER/ PRESENTATION/NHS LIST PRICE: EU/1/19/1404/001: RINVOQ 15 mg prolonged-release tablets in cartons of 28 tablets: £805.56 DATE OF REVISION: December 2020PI-RINVOQ-003

Adverse events should be reported. Reporting forms and information can be found at

https://yellowcard.mhra.gov.uk. Adverse events should also be reported to AbbVie on

GBPV@abbvie.com.