AbbVie to Present Analysis Evaluating Continuous RINVOQ® (upadacitinib) Treatment in Psoriatic Arthritis for More Than One Year at EULAR 2021 Virtual Congress

- In SELECT-PsA 2, 29 percent of bDMARD-IR patients treated with continuous RINVOQ (upadacitinib, 15 mg, once daily) achieved minimal disease activity at 56 weeks, which was consistent with improvements from baseline seen at week 24[1],[2]

- The safety results of RINVOQ 15 mg were consistent with previously reported results in rheumatoid arthritis, with no new significant safety risks identified[1],[3]

- Full results to be presented at the EULAR 2021 Virtual Congress

- RINVOQ is the first oral, once-daily, selective and reversible JAK inhibitor approved for three adult rheumatic indications in the European Union: rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis[2]

News provided by

AbbVie

Jun 02, 2021, 07:30 ET

NORTH CHICAGO, Ill., June 2, 2021 /PRNewswire/ -- AbbVie (NYSE: ABBV) today announced results of an analysis from the Phase 3 SELECT-PsA 2 clinical trial, showing that continuous treatment with RINVOQ^®(upadacitinib, 15 mg, once daily) resulted in sustained improvements in disease activity for more than one year (56 weeks) among patients with active psoriatic arthritis who have responded inadequately to one or more biologic disease modifying anti-rheumatic drugs (bDMARDs).¹ At week 56, 29 percent of patients treated with continuous RINVOQ 15 mg achieved minimal disease activity^a (MDA).¹ Results at week 56 were not multiplicity controlled.¹ The full, long-term results from the Phase 3 SELECT-PsA 2 clinical trial will be presented at the EULAR 2021 Virtual Congress. These results were also recently published online in Rheumatology and Therapy in April 2021.⁴

"We are pleased to share results showing that RINVOQ maintained improvements in these diverse musculoskeletal and skin symptoms of psoriatic arthritis over time," said Mudra Kapoor, M.D., rheumatology head, global medical affairs, AbbVie. "Building upon the recent approval of RINVOQ for psoriatic arthritis in the EU, these results further reinforce the critical role RINVOQ can play in providing adequate disease control that is maintained over time in multiple signs and symptoms of psoriatic arthritis."

In SELECT-PsA 2, 60 percent of patients treated with continuous RINVOQ 15 mg achieved ACR20 response at week 56.¹ Additionally, 41 percent/24 percent of patients treated with continuous RINVOQ achieved ACR50/ACR70 response, respectively.¹ The proportion of patients achieving resolution of enthesitis, dactylitis and improvements from baseline in skin clearance (as measured by PASI 75/90/100) was maintained in patients treated with continuous RINVOQ 15 mg.¹

*SELECT-PsA 2 Efficacy Results Observed at Week 56^,1**
	RINVOQ 15 mg (n=211)
MDA^a	29%
ACR20^b	60%
ACR50^b	41%
ACR70^b	24%

* Efficacy data reported based on randomized treatment. For patients who were discontinued from study medication, non-responder imputation (NRI) was used for binary endpoints. All reported endpoints were not controlled for multiplicity.

^aMDA is defined as the fulfillment of 5 of 7 outcome measures: TJC ≤1; SJC ≤1; PASI ≤1 or BSA-Ps ≤3 percent; Patient's Assessment of Pain NRS ≤1.5; PtGA-Disease Activity NRS ≤2.0; HAQ-DI score ≤0.5; and LEI (Leeds Enthesitis Index) ≤1.

^bACR20/50/70 is defined as at least a 20 percent/50 percent/70 percent reduction from baseline in the number of both tender and swollen joint counts and equivalent improvement in three or more of the five remaining American College of Rheumatology core set measures: patient assessments of pain, global disease activity, physical function, physician global assessment of disease activity and acute phase reactant.

"Managing psoriatic arthritis can be complex due to persistent musculoskeletal and skin symptoms, often causing pain and loss of physical function," said Philip Mease, M.D., director of the Rheumatology Research Division at Swedish Medical Center/Providence St. Joseph Health. "These data show that RINVOQ was able to maintain symptom improvement of psoriatic arthritis over one year with no new significant safety signals. RINVOQ can be an important treatment option to help rheumatologists provide their patients with long-term maintenance of improvements in disease activity."

Safety results of RINVOQ 15 mg at week 24 have been previously reported and were consistent with those observed in the rheumatoid arthritis clinical trial program, with no new significant safety risks identified.^1,3 At week 56, the rate of serious infections was 2.6 events/100PY on RINVOQ 15 mg.¹ The rate of major adverse cardiovascular events was 0.2/100PY and the rate of venous thromboembolic events was 0.2/100PY.¹ There were no deaths reported in the RINVOQ 15 mg group through week 56.¹

AbbVie has previously announced top-line data from SELECT-PsA 2 showing that RINVOQ met the primary endpoint of ACR20 response and all key ranked secondary endpoints versus placebo.⁵

About Psoriatic Arthritis

Psoriatic arthritis is a heterogeneous, systemic inflammatory disease with hallmark manifestations across multiple domains including joints and skin.^6,7 In psoriatic arthritis, the immune system creates inflammation that can lead to pain, fatigue, stiffness in the joints and cause a red, scaly rash.^6,7

About SELECT-PsA 2^1,8

SELECT-PsA 2 is a Phase 3, multicenter, randomized, double-blind, parallel-group, placebo-controlled study designed to evaluate the safety and efficacy of RINVOQ in adult patients with active psoriatic arthritis who have a history of inadequate response to at least one biologic (bDMARD). Patients were initially randomized to RINVOQ 15 mg, upadacitinib 30 mg or placebo followed by either RINVOQ 15 mg or upadacitinib 30 mg at week 24.

The primary endpoint was the percentage of subjects achieving an ACR20 response after 12 weeks of treatment. Key secondary endpoints included change from baseline in HAQ-DI, proportion of patients achieving ACR50 and ACR70 at week 12, proportion of patients achieving PASI 75 at week 16, as well as proportion of patients achieving MDA at week 24. These are not all of the secondary endpoints. The trial is ongoing, and the long-term extension will provide data on the long-term safety, tolerability and efficacy of RINVOQ in patients who have completed the placebo-controlled period.

More information on this trial can be found at www.clinicaltrials.gov (NCT03104374).

About RINVOQ^® (upadacitinib)

Discovered and developed by AbbVie scientists, RINVOQ is a selective and reversible JAK inhibitor that is being studied in several immune-mediated inflammatory diseases.^2,9-15 In human cellular assays, RINVOQ preferentially inhibits signaling by JAK1 or JAK1/3 with functional selectivity over cytokine receptors that signal via pairs of JAK2.² In August 2019, RINVOQ received U.S. FDA approval for adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to methotrexate. RINVOQ is approved by the European Commission for the treatment of adult patients with moderate to severe active rheumatoid arthritis who have responded inadequately to, or who are intolerant to one or more disease-modifying anti-rheumatic drugs (DMARDs); for the treatment of active psoriatic arthritis (PsA) in adult patients who have responded inadequately to, or who are intolerant to one or more DMARDs; and for the treatment of active ankylosing spondylitis (AS) in adult patients who have responded inadequately to conventional therapy. The approved dose for RINVOQ is 15 mg. Phase 3 trials of RINVOQ in atopic dermatitis, axial spondyloarthritis, Crohn's disease, ulcerative colitis, giant cell arteritis and Takayasu arteritis are ongoing.^10-15

Important EU Safety Information about RINVOQ^® (upadacitinib)²

RINVOQ is contraindicated in patients hypersensitive to the active substance or to any of the excipients, in patients with active tuberculosis (TB) or active serious infections, in patients with severe hepatic impairment, and during pregnancy.

Use in combination with other potent immunosuppressants is not recommended.

Serious and sometimes fatal infections have been reported in patients receiving upadacitinib. The most frequent serious infections reported included pneumonia and cellulitis. Cases of bacterial meningitis have been reported. Among opportunistic infections, TB, multidermatomal herpes zoster, oral/oesophageal candidiasis, and cryptococcosis have been reported with upadacitinib. Prior to initiating upadacitinib, consider the risks and benefits of treatment in patients with chronic or recurrent infection or with a history of a serious or opportunistic infection, in patients who have been exposed to TB or have resided or travelled in areas of endemic TB or endemic mycoses, and in patients with underlying conditions that may predispose them to infection. Upadacitinib therapy should be interrupted if a patient develops a serious or opportunistic infection. As there is a higher incidence of infections in patients ≥75 years of age, caution should be used when treating this population.

Patients should be screened for TB before starting upadacitinib therapy. Anti-TB therapy should be considered prior to initiation of upadacitinib in patients with previously untreated latent TB or in patients with risk factors for TB infection.

Viral reactivation, including cases of herpes zoster, were reported in clinical studies. The risk of herpes zoster appears to be higher in Japanese patients treated with upadacitinib. Consider interruption of therapy if a patient develops herpes zoster until the episode resolves. Screening for viral hepatitis and monitoring for reactivation should be performed before starting and during therapy with upadacitinib.

The 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 immunizations, including prophylactic zoster vaccinations, prior to initiating upadacitinib, in agreement with current immunization guidelines.

The risk of malignancies, including lymphoma is increased in patients with rheumatoid arthritis (RA). Immunomodulatory medicinal products may increase the risk of malignancies, including lymphoma. The clinical data are currently limited and long-term studies are ongoing. Malignancies, including non-melanoma skin cancer (NMSC), have been reported in patients treated with upadacitinib. Consider the risks and benefits of upadacitinib treatment prior to initiating therapy in patients with a known malignancy other than a successfully treated NMSC or when considering continuing upadacitinib therapy in patients who develop a malignancy. Periodic skin examination is recommended for patients who are at increased risk for skin cancer.

Absolute neutrophil count <1000 cells/mm³, absolute lymphocyte count <500 cells/mm³, or haemoglobin levels <8 g/dL were reported in <1% of patients in clinical trials. Treatment should not be initiated, or should be temporarily interrupted, in patients with these haematological abnormalities observed during routine patient management.

RA patients have an increased risk for cardiovascular disorders. Patients treated with upadacitinib should have risk factors (e.g., hypertension, hyperlipidaemia) managed as part of usual standard of care.

Upadacitinib treatment was associated with increases in lipid parameters, including total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. The effect of these lipid parameter elevations on cardiovascular morbidity and mortality has not been determined.

Treatment with upadacitinib was associated with an increased incidence of liver enzyme elevation compared to placebo. If increases in ALT or AST are observed during routine patient management and drug-induced liver injury is suspected, upadacitinib therapy should be interrupted until this diagnosis is excluded.

Events of deep vein thrombosis (DVT) and pulmonary embolism (PE) have been reported in patients receiving JAK inhibitors, including upadacitinib. Upadacitinib should be used with caution in patients at high risk for DVT/PE. Risk factors that should be considered in determining the patient's risk for DVT/PE include older age, obesity, a medical history of DVT/PE, patients undergoing major surgery, and prolonged immobilisation. If clinical features of DVT/PE occur, upadacitinib treatment should be discontinued and patients should be evaluated promptly, followed by appropriate treatment.

The most commonly reported adverse drug reactions were upper respiratory tract infections, bronchitis, nausea, blood creatine phosphokinase (CPK) increased and cough. The most common serious adverse reactions were serious infections.

Overall, the safety profile observed in patients with active psoriatic arthritis treated with upadacitinib 15 mg was consistent with rheumatoid arthritis. A higher incidence of acne and bronchitis was observed in patients treated with upadacitinib compared to placebo. A higher rate of serious infections and hepatic transaminase elevations was observed in patients treated with upadacitinib in combination with MTX compared to monotherapy. There was a higher rate of serious infections in patients ≥65 years of age, although data are limited.

Please see the full SmPC for complete prescribing information at http://www.EMA.europa.eu.

Globally, prescribing information varies; refer to the individual country product label for complete information.

About AbbVie in Rheumatology

For more than 20 years, AbbVie has been dedicated to improving care for people living with rheumatic diseases. Our longstanding commitment to discovering and delivering transformative therapies is underscored by our pursuit of cutting-edge science that improves our understanding of promising new pathways and targets in order to help more people living with rheumatic diseases reach their treatment goals. For more information on AbbVie in rheumatology, visit https://www.abbvie.com/our-science/therapeutic-focus-areas/immunology/immunology-focus-areas/rheumatology.html.

About AbbVie

AbbVie's mission is to discover and deliver innovative medicines that solve serious health issues today and address the medical challenges of tomorrow. We strive to have a remarkable impact on people's lives across several key therapeutic areas: immunology, oncology, neuroscience, eye care, virology, women's health and gastroenterology, in addition to products and services across its Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on Twitter, Facebook, Instagram, YouTube and LinkedIn.

Forward-Looking Statements

Some statements in this news release are, or may be considered, forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words "believe," "expect," "anticipate," "project" and similar expressions, among others, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those indicated in the forward-looking statements. Such risks and uncertainties include, but are not limited to, failure to realize the expected benefits from AbbVie's acquisition of Allergan plc ("Allergan"), failure to promptly and effectively integrate Allergan's businesses, competition from other products, challenges to intellectual property, difficulties inherent in the research and development process, adverse litigation or government action, changes to laws and regulations applicable to our industry and the impact of public health outbreaks, epidemics or pandemics, such as COVID-19. Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie's operations is set forth in Item 1A, "Risk Factors," of AbbVie's 2020 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission, as updated by its subsequent Quarterly Reports on Form 10-Q. AbbVie undertakes no obligation to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law.

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