New Long-Term Efficacy and Safety Analyses Evaluating RINVOQ[®] ▼ (upadacitinib) in Patients with Rheumatoid Arthritis to be Presented at EULAR 2021 Virtual Congress
- Long-term data from the Phase 3 SELECT-COMPARE trial show that continuous treatment with upadacitinib plus methotrexate (MTX) maintained rates of clinical remission and low disease activity through three years in adults with rheumatoid arthritis1
- In a separate integrated safety analysis of upadacitinib, no new significant safety findings were observed up to 4.5 years in patients with rheumatoid arthritis2
- Results from both presentations will be shared at the EULAR 2021 Virtual Congress
- Upadacitinib is an oral, once-daily, selective and reversible JAK inhibitor approved in the UK for treatment of patients with severe active rheumatoid arthritis3
MAIDENHEAD, UK, June 3, 2021 – AbbVie (NYSE: ABBV) has 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 upadacitinib 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 care goals aimed at remission or low disease activity,” said Belinda Byrne, Medical Director, AbbVie UK. “These data reinforce the long-term efficacy and safety profile of upadacitinib in rheumatoid arthritis. We continue to advance research to provide valuable insights into the role that upadacitinib has in helping patients with rheumatoid arthritis.”
SELECT-COMPARE Results at Three Years
In this study, a higher proportion of patients treated with upadacitinib 15 mg achieved and maintained clinical remission and low disease activity compared to those treated with adalimumab, through three years.1
|Efficacy Results from SELECT-COMPARE at 3 Years*,1|
|Upadacitinib 15 mg plus MTX||Adalimumab 40 mg every other week plus MTX|
|Clinical remission per DAS28-CRP<2.6a||32%||22%|
|Clinical remission per CDAI≤2.8b||24%||17%|
|Low Disease Activity per DAS28-CRP≤3.2c||37%||26%|
|Low Disease Activity per CDAI≤10d||39%||29%|
*Efficacy data reported based on randomized treatment groups.
For patients who were rescued or prematurely discontinued, non-responder imputation (NRI) was used for binary endpoints. Patients who received adalimumab were switched to receive upadacitinib 15 mg, and vice versa, if they did not achieve at least a 20 percent improvement in both tender and swollen joint count at weeks 14, 18 or 22 compared to baseline, or if Clinical Disease Activity Index (CDAI) was greater than 10 at week 26.
aClinical remission per DAS28-CRP is defined as Disease Activity Score with 28 joint counts C-reactive protein (DAS28-CRP) less than 2.6.
bClinical remission per CDAI is defined as CDAI less than or equal to 2.8.
cLow Disease Activity per DAS28-CRP is defined as Disease Activity Score with 28 joint counts C-reactive protein (DAS28-CRP) less than or equal to 3.2.
dLow Disease Activity per CDAI is defined as CDAI less than or equal to 10.
In addition to higher rates of clinical remission and low disease activity, a higher proportion of patients treated with upadacitinib 15 mg completed three years of treatment without rescue compared to those treated with adalimumab (46 percent versus 34 percent, respectively).1
In this study, through three years, the safety profile of upadacitinib 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 upadacitinib and adalimumab groups.1,2,4,5 Higher rates of herpes zoster, lymphopenia, hepatic disorder and blood creatine phosphokinase (CPK) increase were reported among the upadacitinib 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 upadacitinib compared to 14.1 events/100PY for adalimumab.1 The rate of serious infections was 3.0 events/100PY on upadacitinib and 3.5 events/100PY on adalimumab.1 The rate of deaths was 0.6/100PY on upadacitinib and 0.9/100PY on adalimumab, including non-treatment emergent deaths.1 The rate of major adverse cardiac events (MACE) on both upadacitinib and adalimumab was 0.4/100PY.1 The rate of venous thromboembolic events (VTE) was 0.3/100PY on upadacitinib and 0.5/100PY on adalimumab.1 For both upadacitinib and adalimumab, the rate of malignancy (excluding non-melanoma skin cancer) was 0.4/100PY.1
AbbVie previously announced top-line data from the SELECT-COMPARE trial showing that upadacitinib 15 mg met the primary endpoints of ACR20 response and clinical remission versus placebo, as well as all ranked secondary endpoints versus placebo or adalimumab at week 12.6 ACR20/50/70 is defined as American College of Rheumatology 20 percent/50 percent/70 percent improvements in both tender and swollen joint counts, plus 3 of the following: patient assessments of pain, global disease activity and physical function, physician global assessment of disease activity and acute phase reactant (high sensitivity c-reactive protein). These results were also published in Arthritis and Rheumatology.6
Integrated Safety Analysis up to 4.5 Years
An integrated safety analysis including safety data across upadacitinib rheumatoid arthritis studies showed that the safety profile of upadacitinib 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 patient years of exposure of upadacitinib 15 mg, as well as data of adalimumab and MTX.2 In this integrated safety analysis, results showed that the safety profiles of upadacitinib 15 mg and adalimumab were generally similar, with the exception of higher rates of herpes zoster and blood CPK increase seen with upadacitinib 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 upadacitinib 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 upadacitinib and comparator-treatment groups.2 The rate of deaths in upadacitinib-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 and approximately 400 thousand people in the UK.10,11,12 As the most common form of autoimmune arthritis, it causes pain, stiffness, swelling and loss of function in the joints.10,13 Many patients with rheumatoid arthritis still do not achieve clinical remission or low disease activity targets.14
SELECT-COMPARE is a Phase 3, multicenter, randomized, double-blind study designed to evaluate the safety and efficacy of upadacitinib compared to placebo and adalimumab in adult patients with moderate to severe active rheumatoid arthritis who had an inadequate response to methotrexate and continued a stable background of MTX. Patients received background MTX and were randomized 2:2:1 to receive upadacitinib (15 mg, once daily), placebo or adalimumab (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 Modified Total Sharp Score (mTSS) compared to placebo and a comparison versus adalimumab in percentage of subjects achieving ACR50, low disease activity, changes in pain as measured by the Patient's Assessment of Pain (based on Visual Analog Scale (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 upadacitinib rheumatoid arthritis clinical trials. Treatment-emergent adverse events, including adverse events of special interest were summarized for upadacitinib 15 mg (pooled), upadacitinib 30 mg (pooled), MTX and adalimumab. 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.
Upadacitinib is a once-daily, oral, selective, and reversible Janus Kinase (JAK) inhibitor. It received marketing authorisation in December 2019 for the treatment of adult patients with moderate to severe active RA, who have had an inadequate response or are intolerant to one or more disease modifying anti-rheumatic drugs (DMARDs) and it may be used as monotherapy or in combination with the DMARD methotrexate. Both NICE and the SMC have issued positive recommendations for the use of upadacitinib in severe active RA.3,17 Upadacitinib prescribing information (PI) can be found at: https://www.medicines.org.uk/emc/product/10972/smpc
Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. Adverse events should also be reported to AbbVie UK Ltd. Please contact GBPV@abbvie.com.
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.
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.co.uk. Follow @abbvieUK on Twitter.
UK media contacts:
T: +44 (0)7795 590344
T: +44 (0)7392 125 460
Fleischmann, R., et al. Long-Term Safety and Efficacy of Upadacitinib or Adalimumab in Patients with Rheumatoid Arthritis: Results at 3 years From the SELECT-COMPARE Study. 2021 EULAR Congress; POS0087.
- Cohen, S., et al. Integrated Safety Profile of Upadacitinib With up to 4.5 Years of Exposure in Patients With Rheumatoid Arthritis (RA Integrated Safety Update). 2021 EULAR Congress; POS0220.
- NCIE Guidance for Upadacitinib for treating severe rheumatoid arthritis. Available at: https://www.nice.org.uk/guidance/ta665/chapter/1-Recommendations. Accessed on June 2, 2021.
- Cohen S., et al. Safety profile of upadacitinib in rheumatoid arthritis: integrated analysis from the SELECT phase III clinical programme. Ann Rheum Dis. 2020 Oct 28;80(3):304-11.
- Fleischmann R., et al. Long-Term Safety and Effectiveness of Upadacitinib or Adalimumab in Patients with Rheumatoid Arthritis: Results at 72 weeks from the SELECT-COMPARE Study. 2020 EULAR E-Congress; THU0201.
- Fleischmann, R., et al. Upadacitinib Versus Placebo or Adalimumab in Patients With Rheumatoid Arthritis and an Inadequate Response to Methotrexate: Results of a Phase III, Double-Blind, Randomized Controlled Trial. Arthritis Rheumatol. 2019 Nov;71(11):1788-1800. doi: 10.1002/art.41032.
- Kim S.C. Risk of Venous Thromboembolism in Patients with Rheumatoid Arthritis. Arthritis Care & Research. Vol. 65, No. 10, October 2013, pp 1600–1607.
- AbbVie. Data on File, ABVRRTI64959.
- AbbVie. Data on File, ABVRRTI66056.
- American College of Rheumatology. “Rheumatoid Arthritis.” 2021. Available at: https://www.rheumatology.org/I-Am-A/Patient-Caregiver/Diseases-Conditions/Rheumatoid-Arthritis. Accessed April 11, 2021.
- World Health Organization. The Global Burden of Disease, 2004 Update. Available at: http://www.who.int/healthinfo/global_burden_disease/GBD_report_2004update_full.pdf. Accessed on April 11, 2021.
- NICE. Adalimumab, etanercept, infliximab, certolizumab pegol, golimumab, tocilizumab and abatacept for rheumatoid arthritis not previously treated with DMARDs or after conventional DMARDs only have failed (TA375). January 2016 https://www.nice.org.uk/guidance/ta375/chapter/2-Clinical-need-and-practice. Accessed on June 2, 2021.
- Singh et al. 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Care & Research. 2015;10;1-25.
- Ajeganova S. and Huizinga T. Sustained remission in rheumatoid arthritis: latest evidence and clinical considerations. Ther Adv Musculoskelet Dis. 2017 Oct;9(10):249-262. doi: 10.1177/1759720X17720366.
- A Study Comparing Upadacitinib (ABT-494) to Placebo and to Adalimumab in Adults With Rheumatoid Arthritis Who Are on a Stable Dose of Methotrexate and Who Have an Inadequate Response to Methotrexate (SELECT-COMPARE). ClincialTrials.gov. 2021. Available at: https://clinicaltrials.gov/ct2/show/NCT02629159. Accessed on April 11, 2021.
- RINVOQ 15 mg prolonged-release tablets SMPC, https://www.medicines.org.uk/emc/product/10972/smpc. Access on June 2, 2021.
- SMC medicines advice for upadacitnib treatment of rheumatoid arthritis. Available at https://www.scottishmedicines.org.uk/medicines-advice/upadacitinib-rinvoq-full-smc2315/. Accessed on June 2, 2021.