RINVOQ®, the 15mg once-daily oral selective & reversible JAK inhibitor.1
RINVOQ is indicated for the treatment of moderate to severe active rheumatoid arthritis 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.1
Below are results from the long-term extension of
SELECT-COMPARE:
RINVOQ offers RA patients a SIGNIFICANTLY GREATER REMISSION RATE at Week 12 vs placebo and through Week 156 vs adalimumab (all groups on background MTX)1,4
SELECT-COMPARE: Remission (DAS28 [CRP] <2.6) rates over time NRI1,2,4,5
The primary (EMA) multiplicity-controlled endpoint of SELECT-COMPARE, Week 12: clinical remission (DAS28 [CRP] <2.6) vs placebo + MTX was met. All other data shown between Week 12 and Week 48 were prespecified, non-ranked, non-multiplicity controlled endpoints: nominal P-values are provided. Data after Week 48 were non-ranked, non-multiplicity-controlled endpoints obtained from the ongoing open-label long-term extension of SELECT-COMPARE.4 In patients with moderate to severe active RA and inadequate response to MTX.1
*P≤0.01 vs placebo + MTX.2 †P≤0.001 vs placebo + MTX.2 ‡P≤0.01 vs adalimumab + MTX.2 §P≤0.001 vs adalimumab + MTX.2 IIP<0.001 vs adalimumab + MTX.4 ¥P<0.01 vs adalimumab + MTX.4 ¶Indicates multiplicity-controlled comparison of RINVOQ + MTX vs placebo + MTX.2 **Vertical line at Week 26 indicates the end of the placebo-controlled period.4 ***Vertical line at Week 48 indicates the start of the long-term extension phase.4 #61% is the relative difference between 29% (RINVOQ + MTX) and 18% (adalimumab + MTX) of patients who achieved remission (DAS28 [CRP] <2.6) at Week 12.5
Treatment groups are by initial randomisation and NRI was applied for rescue, premature discontinuation of study drug, and missing data. 252/651 and 159/327 patients were rescued of those randomised to RINVOQ and adalimumab, respectively.4
DAS28 (CRP), Disease Activity Score with 28-Joint Count (C-Reactive Protein); EMA, European Medicines Agency; EOW, Every Other Week; MTX, Methotrexate; NRI, Non-Responder Imputation; QD, Once-Daily; RA, Rheumatoid Arthritis.
RINVOQ + MTX demonstrated SIGNIFICANTLY HIGHER levels of clinical response (ACR50/Pain/Function) compared to adalimumab + MTX at Week 1564
SELECT-COMPARE LONG-TERM EXTENSION: ACR50, pain and HAQ-DI at Week 1564
In patients with moderate to severe active RA and inadequate response to MTX.1 *P<0.001 vs adalimumab + MTX: nominal P-value.4 †P<0.01 vs adalimumab + MTX: nominal P-value.4
ACR50: Treatment groups are by initial randomisation, and NRI was used for missing data as well as patients who were rescued prior to/at Week 26.4 Pain/HAQ-DI: Treatment groups are by initial randomisation. Observations after rescue were replaced with the last observation prior to rescue.4
ACR50, Improvement of at least 50% in the American College of Rheumatology core criteria; ANCOVA, Analysis of Covariance; EOW, Every Other Week; HAQ-DI, Health Assessment Questionnaire Disability Index; MTX, Methotrexate; NRI, Non-Responder Imputation; QD, Once-Daily; RA, Rheumatoid Arthritis.
RINVOQ + MTX demonstrated HIGHER REMISSION RATES vs adalimumab + MTX across multiple measures at Week 726
SELECT-COMPARE: Remission rates at Week 72 (NRI)6
All data shown were prespecified nonranked non-multiplicity controlled endpoints: nominal P-values are provided.6 In patients with moderate to severe active RA and inadequate response to MTX.1 *P≤0.001 vs adalimumab + MTX:6 nominal P-value.6 †P≤0.05 vs adalimumab + MTX:6 nominal P-value.6 ‡ACR/EULAR Boolean definition of remission: at any point a patient must satisfy all of the following: TJC28 ≤1, SJC28 ≤1, CRP ≤1mg/dL, and PGA of disease activity ≤1 (on a 0-10cm VAS).2
ACR, American College of Rheumatology; CDAI, Clinical Disease Activity Index; CRP, C-Reactive Protein; EOW, Every Other Week; EULAR, European League Against Rheumatism; MTX, Methotrexate; NRI, Non-Responder Imputation; PGA, Patient Global Assessment; QD, Once-Daily; RA, Rheumatoid Arthritis; SDAI, Simplified Disease Activity Index; SJC28, Swollen Joint Count in 28 joints; TJC28, Tender Joint Count in 28 joints; VAS, Visual Analogue Scale.
RINVOQ + MTX was effective in inhibiting the PROGRESSION OF STRUCTURAL JOINT DAMAGE in patients with an inadequate response to MTX, through Week 967
SELECT-COMPARE: Radiographic progression at Week 96 (as observed)7
In patients with moderate to severe active RA and inadequate response to MTX.1 *Includes all patients receiving placebo who were not previously rescued at Week 14, 18 or 22 and were switched to RINVOQ at Week 26 regardless of response.7 †Continuous adalimumab and RINVOQ groups include only those patients initially randomised to these treatment groups who remained on their initially randomised treatment throughout the study.7 No statistical comparisons were made between RINVOQ and adalimumab groups for radiographic endpoints.7
EOW, Every Other Week; LS, Least Squares; mTSS, modified Total Sharp Score; MTX, Methotrexate; QD, Once-Daily; RA, Rheumatoid Arthritis.
Special warnings and precautions for use1
The most commonly reported adverse drug reactions are upper respiratory tract infections, nausea, blood creatine phosphokinase (CPK) increased and cough. The most common serious adverse reactions were serious infections.
Contraindications: Hypersensitivity to active substance or excipients, active tuberculosis (TB) or active serious infections, severe hepatic impairment and pregnancy.
Serious infections: Closely monitor patients for the development of signs and symptoms of infection during and after treatment with RINVOQ. Treatment should be interrupted if a patient develops a serious or opportunistic infection and until the infection is controlled. As there is a higher incidence of infections in the elderly ≥75 years of age, caution should be used when treating this population.
Tuberculosis (TB): Patients should be screened for TB before starting on RINVOQ. RINVOQ should not be given to patients with active TB. Anti-TB therapy should be considered prior to initiation of RINVOQ in patients with previously untreated latent TB, or in patients with risk factors for TB infection. 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: Screening for viral hepatitis and monitoring for reactivation should be performed before starting and during therapy with RINVOQ. lf a patient develops herpes zoster, consider interruption of RINVOQ therapy until the episode resolves. If hepatitis B virus DNA is detected while receiving RINVOQ, a liver specialist should be consulted.
Venous thromboembolism: RINVOQ should be used with caution in patients at high risk for deep venous thrombosis (DVT)/pulmonary embolism (PE). lf clinical features of DVT/PE occur, RINVOQ treatment should be discontinued and patients should be evaluated promptly, followed by appropriate treatment. 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.
Malignancy: Malignancies were observed in clinical studies. Periodic skin examination is recommended for patients who are at increased risk for skin cancer.
Cardiovascular risk: Patients treated with RINVOQ should have risk factors (e.g., hypertension, hyperlipidaemia) managed as part of usual standard of care.
Vaccinations: Use of live, attenuated vaccines during or immediately prior to RINVOQ therapy is not recommended. Prior to initiating RINVOQ, it is recommended that patients be brought up to date with all immunisations, including prophylactic zoster vaccinations, in agreement with current immunisation guidelines.
lmmunosuppressive medicinal products: Combination with other potent immunosuppressants such as azathioprine, ciclosporin, tacrolimus, and bDMARDs or other JAK inhibitors has not been evaluated in clinical studies and is not recommended as a risk of additive immunosuppression cannot be excluded.
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.
Absolute Neutrophil Count (ANC), Absolute Lymphocyte Count (ALC) and haemoglobin levels: ANC <1 x109 cells/L, ALC <0.5 x 109 cells/L and haemoglobin levels <8 d/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.
Lipids: RINVOQ 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.
References
- RINVOQ (upadacitinib) Summary of Product Characteristics, available at www.medicines.ie.
- Fleischmann R, Pangan AL, Song IH, 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; 71(11): 1788-1800.
- Fleischmann RM, Genovese MC, Enejosa JV, et al. Safety and effectiveness of upadacitinib or adalimumab plus methotrexate in patients with rheumatoid arthritis over 48 Weeks with switch to alternate therapy in patients with insufficient response. Ann Rheum Dis. 2019; 78(11): 1454-1462.
- Fleischmann R, Mysler E, Bessette L, et al. POS0087. Long-Term Safety and Efficacy of Upadacitinib or Adalimumab in Patients With Rheumatoid Arthritis: Results at 3 Years From the SELECT-COMPARE Study. Poster presented at: EULAR 2021.
- AbbVie. Data on File. ABVRRTI72704. SELECT COMPARE (Ml4-465) efficacy data up to 156 weeks DAS28-CRP, CDAI. (Full Analysis Set).
- Fleischmann R, Song IH, Enejosa J, et al. THU0201. Long-term safety and effectiveness of upadacitinib or adalimumab in patients with rheumatoid arthritis: results at 72 weeks from the SELECT-COMPARE study. Annals of the Rheumatic Diseases. 2020; 79: 323.
- Peterfy CG, Strand V, Genovese MC, et al. Radiographic Outcomes in Patients With Rheumatoid Arthritis Receiving Upadacitinib as Monotherapy or in Combination With Methotrexate: Results at 2 Years From the SELECT-COMPARE and SELECT-EARLY Studies. THU0211. Poster presented at, EULAR 2020.
Date of preparation: January 2022 IE-RNQR-200094
Legal Category: POM (S1A).
Further information is available on request from AbbVie Limited, 14 Riverwalk, Citywest Business Campus, Dublin 24, Ireland.
