New Long-Term Efficacy and Safety Analyses Evaluating RINVOQ® (upadacitinib) in Patients with Rheumatoid Arthritis to be Presented at EULAR 2021 Virtual Congress

NORTH CHICAGO, Ill., June 2, 2021 /PRNewswire/ -- AbbVie (NYSE: ABBV) today announced new analyses to be presented at the EULAR 2021 Virtual Congress showing patients with moderate to severe rheumatoid arthritis on background methotrexate (MTX) treated with RINVOQ^® (upadacitinib, 15 mg, once daily) maintained higher rates of clinical remission and low disease activity through three years compared to those patients treated with HUMIRA^® (adalimumab).¹ Additionally, a separate integrated safety analysis found the safety profile of RINVOQ was consistent over 4.5 years, with no new safety risks observed.²

"We are dedicated to helping more people living with rheumatoid arthritis reach their treatment goals aimed at remission or low disease activity," said Mudra Kapoor, M.D., rheumatology head, global medical affairs, AbbVie. "These data reinforce the long-term efficacy and safety profile of RINVOQ in rheumatoid arthritis. We continue to advance research to provide valuable insights into the role that RINVOQ has in helping patients with moderate to severe rheumatoid arthritis."

SELECT-COMPARE Results at Three Years

In this study, a higher proportion of patients treated with RINVOQ 15 mg achieved and maintained clinical remission and low disease activity compared to those treated with HUMIRA, through three years.¹

In addition to higher rates of clinical remission and low disease activity, a higher proportion of patients treated with RINVOQ 15 mg completed three years of treatment without rescue compared to those treated with HUMIRA (46 percent versus 34 percent, respectively).¹

In this study, through three years, the safety profile of RINVOQ 15 mg was consistent with the profile reported previously and with that shown in the Phase 3 integrated safety analysis.^1,2,4,5 Additionally, the rates of events of special interest were generally comparable between the RINVOQ and HUMIRA groups.^1,2,4,5 Higher rates of herpes zoster, lymphopenia, hepatic disorder and blood creatine phosphokinase (CPK) increase were reported among the RINVOQ group.^1,2,4,5 The majority of herpes zoster and hepatic disorder cases were non-serious.¹ Patients with blood CPK increase were usually asymptomatic and no cases of rhabdomyolysis were reported.¹ Serious adverse events occurred at 10.9 events per 100 patient years (100PY) for RINVOQ compared to 14.1 events/100PY for HUMIRA.¹ The rate of serious infections was 3.0 events/100PY on RINVOQ and 3.5 events/100PY on HUMIRA.¹ The rate of deaths was 0.6/100PY on RINVOQ and 0.9/100PY on HUMIRA, including non-treatment emergent deaths.¹ The rate of major adverse cardiac events (MACE) on both RINVOQ and HUMIRA was 0.4/100PY.¹ The rate of venous thromboembolic events (VTE) was 0.3/100PY on RINVOQ and 0.5/100PY on HUMIRA.¹ The rate of malignancy (excluding non-melanoma skin cancer) was 0.6/100PY on RINVOQ and 0.7/100PY on HUMIRA.¹

AbbVie previously announced top-line data from SELECT-COMPARE showing that RINVOQ 15 mg met the primary endpoints of ACR20 response and clinical remission versus placebo, as well as all ranked secondary endpoints versus placebo or HUMIRA at week 12.⁶ These results were also published in Arthritis and Rheumatology.

Integrated Safety Analysis up to 4.5 Years

An integrated safety analysis including safety data across RINVOQ rheumatoid arthritis studies showed that the safety profile of RINVOQ 15 mg was consistent with previous analyses, with no new safety risks identified up to 4.5 years of treatment.^2,4 This analysis included data pooled from six rheumatoid arthritis Phase 3 clinical trials and included more than 3,000 patients with over 7,000 PY of exposure of RINVOQ 15 mg, as well as data of HUMIRA and MTX.² In this integrated safety analysis, results showed that the safety profiles of RINVOQ 15 mg and HUMIRA were generally similar, with the exception of higher rates of herpes zoster and blood CPK increase seen with RINVOQ 15 mg.² Most herpes zoster cases were non-serious (94 percent) and CPK elevations were mostly asymptomatic.² The most common adverse events seen with RINVOQ 15 mg were upper respiratory tract infection, nasopharyngitis and urinary tract infection.² Rates of serious infections, malignancy (excluding non-melanoma skin cancer), MACE and VTE were broadly similar across RINVOQ and comparator-treatment groups.² The rate of deaths in RINVOQ-treated patients with rheumatoid arthritis remains consistent with the background rate for patients with rheumatoid arthritis.^2,7-9

"In SELECT-COMPARE, more than a quarter of patients achieved clinical remission at three years, and the separate integrated safety analysis showed a consistent safety profile for more than four years," said Roy M. Fleischmann, M.D., primary investigator for SELECT-COMPARE and clinical professor at the University of Texas Southwestern Medical Center at Dallas. "In a disease where more than 70 percent of people fail to achieve clinical remission at all, it is encouraging to see efficacy results coupled with a consistent safety profile over this period of time."

About Rheumatoid Arthritis

Rheumatoid arthritis is a chronic and debilitating immune-mediated inflammatory disease that affects an estimated 23.7 million people worldwide.^10,11 As the most common form of autoimmune arthritis, it causes pain, stiffness, swelling and loss of function in the joints.^10,12 Many patients with rheumatoid arthritis still do not achieve clinical remission or low disease activity targets.¹³

About SELECT-COMPARE^1,14

SELECT-COMPARE is a Phase 3, multicenter, randomized, double-blind study designed to evaluate the safety and efficacy of RINVOQ compared to placebo and HUMIRA in adult patients with moderate to severe active rheumatoid arthritis who had an inadequate response to MTX and continued a stable background of MTX. Patients received background MTX and were randomized 2:2:1 to receive RINVOQ (15 mg, once daily), placebo or HUMIRA (given as a subcutaneous injection of 40 mg every other week).

The primary endpoints included the percentage of subjects achieving ACR20 and clinical remission (based on DAS28-CRP) after 12 weeks of treatment compared to placebo. Ranked secondary endpoints included change in the mTSS compared to placebo and a comparison versus HUMIRA in percentage of subjects achieving ACR50, low disease activity, changes in pain as measured by the Patient's Assessment of Pain (based on VAS) and changes in physical function, as measured by the Health Assessment Questionnaire-Disability-Index (HAQ-DI). The trial is ongoing and included a 48-week randomized, double-blind treatment period followed by an ongoing long-term extension study for an overall study length of up to ten years.

More information on this trial can be found at www.clinicaltrials.gov (NCT02629159).

About the Integrated Safety Analysis²

The integrated safety analysis included pooled data from six randomized, controlled RINVOQ rheumatoid arthritis clinical trials. Treatment-emergent adverse events, including adverse events of special interest were summarized for RINVOQ 15 mg (pooled), upadacitinib 30 mg (pooled), MTX and HUMIRA. Treatment-emergent adverse events were reported as exposure adjusted event rates (events/100 PY), which included both incident and recurrent events, up to a cut-off date of June 2020.

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.^3,15-21 In human cellular assays, RINVOQ preferentially inhibits signaling by JAK1 or JAK1/3 with functional selectivity over cytokine receptors that signal via pairs of JAK2.³ 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.^16-21

Important Safety Information about RINVOQ^® (upadacitinib)³

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 ≥65 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.

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

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

About HUMIRA^® in the European Union²²

HUMIRA, in combination with methotrexate, is indicated for the treatment of moderate to severe, active rheumatoid arthritis in adult patients when the response to disease-modifying anti-rheumatic drugs, including methotrexate, has been inadequate.

Important EU Safety Information about HUMIRA^® (adalimumab)

HUMIRA is contraindicated in patients with active tuberculosis or other severe infections such as sepsis, and opportunistic infections and in patients with moderate to severe heart failure (NYHA class III/IV). It is also contraindicated in patients hypersensitive to the active substance or to any of the excipients; serious allergic reactions including anaphylaxis have been reported. The use of HUMIRA increases the risk of developing serious infections, including hepatitis B reactivation, which may, in rare cases, be life-threatening. Rare cases of lymphoma and leukemia have been reported in patients treated with HUMIRA. On rare occasions, a severe type of cancer called hepatosplenic T-cell lymphoma has been observed and often results in death. A risk for the development of malignancies in patients treated with TNF-antagonists cannot be excluded. Rare cases of pancytopenia, aplastic anaemia, demyelinating disease, lupus, lupus-related conditions and Stevens-Johnson syndrome have been reported in patients treated with HUMIRA. The most frequently reported adverse events across all indications included respiratory infections, injection site reactions, headache and musculoskeletal pain.

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, including the impact of the COVID-19 pandemic on AbbVie's operations, results and financial results, 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 of the Allergan acquisition, failure to promptly and effectively integrate Allergan's businesses, significant transaction costs and/or unknown or inestimable liabilities, potential litigation associated with the Allergan acquisition, challenges to intellectual property, competition from other products, difficulties inherent in the research and development process, adverse litigation or government action, and changes to laws and regulations applicable to our industry. 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 (SEC). 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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