COVID-19 Clinical Data
The efficacy and safety of Olumiant were assessed in two phase 3, randomized, double-blind, placebo-controlled clinical trials1:
- ACTT-2 (COVID I, NCT04401579), which evaluated the combination of Olumiant 4 mg and remdesivir compared to placebo and remdesivir.
- COV-BARRIER (COVID II, NCT04421027), which evaluated Olumiant 4 mg compared to placebo. Patients could remain on background therapy, as defined per local guidelines. An additional exploratory sub-study in patients requiring invasive mechanical ventilation or ECMO at baseline was also conducted under this protocol and analyzed separately.
ACTT-2=Adaptive COVID-19 Treatment Trial 2.
NIAID Ordinal Scale used in ACTT-2 and COV-BARRIER1
| 1 | Not hospitalized; no limitations on activities |
| 2 | Not hospitalized; limitation on activities and/or requiring home oxygen |
| 3 | Hospitalized; no longer requires ongoing medical care; not requiring supplemental oxygen |
| 4 | Hospitalized; requiring ongoing medical care; not requiring supplemental oxygen |
| 5 | Hospitalized; requiring supplemental oxygen |
| 6 | Hospitalized; on non-invasive ventilation or high-flow oxygen devices |
| 7 | Hospitalized; on invasive mechanical ventilation or ECMO |
| 8 | Death |
ACTT-2=Adaptive COVID-19 Treatment Trial 2.
SELECT IMPORTANT SAFETY INFORMATION RELATED TO SERIOUS INFECTIONS
The most common serious infections reported with Olumiant included pneumonia, herpes zoster, and urinary tract infection. Among opportunistic infections, tuberculosis, multidermatomal herpes zoster, esophageal candidiasis, pneumocystosis, acute histoplasmosis, cryptococcosis, cytomegalovirus, and BK virus were reported with Olumiant. Some patients have presented with disseminated rather than localized disease, and were often taking concomitant immunosuppressants such as methotrexate or corticosteroids. Avoid Olumiant in patients with an active, serious infection, including localized infections. Consider the risks and benefits of treatment prior to initiating Olumiant. Closely monitor patients for development of infections during and after Olumiant treatment. In COVID-19 patients, consider the risks and benefits of treatment with OLUMIANT with other concurrent infections.
ACTT-2 Data Overview
ACTT-2 (COVID I) Study Design
The Adaptive COVID-19 Treatment Trial 2 (ACTT-2) study was a randomized, double-blind, placebo-controlled clinical trial of hospitalized adults with confirmed SARS-CoV-2 infection that compared treatment with Olumiant and remdesivir (combination group; n=515) to treatment with placebo and remdesivir (placebo group; n=518). Patients had to have laboratory-confirmed SARS-CoV-2 infection*, as well as at least one of the following to be enrolled in the trial: radiographic infiltrates by imaging, SpO2 ≤94% on room air, a requirement for supplemental oxygen, or a requirement for mechanical ventilation or ECMO.1-3
There was no limit to the duration of symptoms prior to enrollment.3
Patients treated with the combination received the following regimen1,2:
- Olumiant 4 mg once daily (orally) for 14 days or until hospital discharge, whichever was first
- Remdesivir 200 mg on Day 1 and 100 mg once daily (via intravenous infusion) on subsequent days for a total treatment duration of 10 days or until hospital discharge, whichever was first
In this study prophylaxis for venous thromboembolic event (VTEs) was recommended for all patients unless a major contraindication was noted.1,2
The primary endpoint, for the intent to treat population, was time to recovery within 29 days after randomization.
Recovery was defined as1-3:
- being discharged from the hospital without limitations on activities
- being discharged from the hospital with limitations on activities and/or requiring home oxygen, or
- hospitalized but not requiring supplemental oxygen and no longer requiring medical care
The key secondary endpoint was clinical status on Day 15, as assessed on an 8-point ordinal scale (OS).1-3
*Laboratory-confirmed SARS-CoV-2 infection was determined by RT-PCR assay.3
ECMO=extracorporeal membrane oxygenation; RT-PCR=reverse transcription, polymerase-chain-reaction; SARS-CoV-2=severe acute respiratory syndrome coronavirus 2; SpO2=peripheral oxygen saturation.
Patient Characteristics for ACTT-2
All subjects (N=1033)
|
Olumiant + RDV (N=515)
|
Placebo + RDV (N=518)
| |
|---|---|---|---|
| Age1,2 | |||
| Mean, years (SD) | All subjects (N=1033): 55.4 (15.7) | Olumiant + RDV (N=515): 55.0 (15.4) | Placebo + RDV (N=518): 55.8 (16.0) |
| Distribution, n (%) | |||
| <40 years | All subjects (N=1033): 173 (16.7) | Olumiant + RDV (N=515): 87 (16.9) | Placebo + RDV (N=518): 86 (16.6) |
| 40-64 years | All subjects (N=1033): 555 (53.7) | Olumiant + RDV (N=515): 281 (54.6) | Placebo + RDV (N=518): 274 (52.9) |
| ≥65 years | All subjects (N=1033): 305 (29.5) | Olumiant + RDV (N=515): 147 (28.5) | Placebo + RDV (N=518): 158 (30.5) |
All subjects (N=1033)
|
Olumiant + RDV (N=515)
|
Placebo + RDV (N=518)
| |
|---|---|---|---|
| Sex, n (%)1,2 | |||
| Male | All subjects (N=1033): 652 (63.1) | Olumiant + RDV (N=515): 319 (61.9) | Placebo + RDV (N=518): 333 (64.3) |
| Female | All subjects (N=1033): 381 (36.9) | Olumiant + RDV (N=515): 196 (38.1) | Placebo + RDV (N=518): 185 (35.7) |
All subjects (N=1033)
|
Olumiant + RDV (N=515)
|
Placebo + RDV (N=518)
| |
|---|---|---|---|
| Race, n (%)1,2a | |||
| Asian | All subjects (N=1033): 101 (9.8) | Olumiant + RDV (N=515): 49 (9.5) | Placebo + RDV (N=518): 52 (10.0) |
| Black | All subjects (N=1033): 156 (15.1) | Olumiant + RDV (N=515): 77 (15.0) | Placebo + RDV (N=518): 79 (15.3) |
| White | All subjects (N=1033): 496 (48.0) | Olumiant + RDV (N=515): 251 (48.7) | Placebo + RDV (N=518): 245 (47.3) |
| Other or Unknown | All subjects (N=1033): 280 (27.1) | Olumiant + RDV (N=515): 138 (26.8) | Placebo + RDV (N=518): 142 (27.4) |
| Ethnic group, n (%)1,2a | |||
| Hispanic or Latino | All subjects (N=1033): 531 (51.4) | Olumiant + RDV (N=515): 263 (51.1) | Placebo + RDV (N=518): 268 (51.7) |
| Not Hispanic or Latino | All subjects (N=1033): 486 (47.0) | Olumiant + RDV (N=515): 246 (47.8) | Placebo + RDV (N=518): 240 (46.3) |
| Not reported or unknown | All subjects (N=1033): 16 (1.5) | Olumiant + RDV (N=515): 6 (1.2) | Placebo + RDV (N=518): 10 (1.9) |
aRace and ethnic group were reported by the patients. With respect to "other" race, the categories that were used when data on race were reported included American Indian or Alaska Native and Native Hawaiian or other Pacific Islander.
All subjects (N=1033)
|
Olumiant + RDV (N=515)
|
Placebo + RDV (N=518)
| |
|---|---|---|---|
| Geographic region, n (%)2 | |||
| Asia | All subjects (N=1033): 67 (6.5) | Olumiant + RDV (N=515): 33 (6.4) | Placebo + RDV (N=518): 34 (6.6) |
| Europe | All subjects (N=1033): 13 (1.3) | Olumiant + RDV (N=515): 6 (1.2) | Placebo + RDV (N=518): 7 (1.4) |
| North America | All subjects (N=1033): 953 (92.3) | Olumiant + RDV (N=515): 476 (92.4) | Placebo + RDV (N=518): 477 (92.1) |
All subjects (N=1033)
|
Olumiant + RDV (N=515)
|
Placebo + RDV (N=518)
| |
|---|---|---|---|
| Time from symptom onset to randomization2 | |||
| Median days (IQR) | All subjects (N=1033): 8 (5-10) | Olumiant + RDV (N=515): 8 (5-10) | Placebo + RDV (N=518): 8 (5-11) |
All subjects (N=1033)
|
Olumiant + RDV (N=515)
|
Placebo + RDV (N=518)
| |
|---|---|---|---|
| Ordinal scale score, n (%)1,2 | |||
| 4 | All subjects (N=1033): 142 (13.7) | Olumiant + RDV (N=515): 70 (13.6) | Placebo + RDV (N=518): 72 (13.9) |
| 5 | All subjects (N=1033): 564 (54.6) | Olumiant + RDV (N=515): 288 (55.9) | Placebo + RDV (N=518): 276 (53.3) |
| 6 | All subjects (N=1033): 216 (20.9) | Olumiant + RDV (N=515): 103 (20.0) | Placebo + RDV (N=518): 113 (21.8) |
| 7 | All subjects (N=1033): 111 (10.7) | Olumiant + RDV (N=515): 54 (10.5) | Placebo + RDV (N=518): 57 (11.0) |
All subjects (N=1033)
|
Olumiant + RDV (N=515)
|
Placebo + RDV (N=518)
| |
|---|---|---|---|
| Comorbidities at baseline, n (%)1,3b | |||
| Obesity | All subjects (N=1033): 567 (56) | Olumiant + RDV (N=515): 295 (58) | Placebo + RDV (N=518): 272 (53) |
| Hypertension | All subjects (N=1033): 522 (52) | Olumiant + RDV (N=515): 258 (51) | Placebo + RDV (N=518): 264 (52) |
| Type 2 diabetes | All subjects (N=1033): 370 (37) | Olumiant + RDV (N=515): 195 (39) | Placebo + RDV (N=518): 175 (35) |
| Coronary artery disease | All subjects (N=1033): 101 (10) | Olumiant + RDV (N=515): 50 (10) | Placebo + RDV (N=518): 51 (10) |
| Asthma | All subjects (N=1033): 97 (10) | Olumiant + RDV (N=515): 53 (10) | Placebo + RDV (N=518): 44 (9) |
| Chronic respiratory disease | All subjects (N=1033): 69 (7) | Olumiant + RDV (N=515): 39 (8) | Placebo + RDV (N=518): 30 (6) |
| Chronic kidney disease | All subjects (N=1033): 64 (6) | Olumiant + RDV (N=515): 31 (6) | Placebo + RDV (N=518): 33 (7) |
| Congestive heart failure | All subjects (N=1033): 62 (6) | Olumiant + RDV (N=515): 31 (6) | Placebo + RDV (N=518): 31 (6) |
| Cancer | All subjects (N=1033): 37 (4) | Olumiant + RDV (N=515): 20 (4) | Placebo + RDV (N=518): 17 (3) |
| Immune deficiency | All subjects (N=1033): 30 (3) | Olumiant + RDV (N=515): 17 (3) | Placebo + RDV (N=518): 13 (3) |
| Chronic liver disease | All subjects (N=1033): 28 (3) | Olumiant + RDV (N=515): 13 (3) | Placebo + RDV (N=518): 15 (3) |
| Any history of DVT or PE | All subjects (N=1033): 22 (2) | Olumiant + RDV (N=515): 11 (2) | Placebo + RDV (N=518): 11 (2) |
| Cardiac valvular disease | All subjects (N=1033): 22 (2) | Olumiant + RDV (N=515): 10 (2) | Placebo + RDV (N=518): 12 (2) |
| Chronic oxygen requirement | All subjects (N=1033): 17 (2) | Olumiant + RDV (N=515): 8 (2) | Placebo + RDV (N=518): 9 (2) |
| Type 1 diabetes | All subjects (N=1033): 10 (1) | Olumiant + RDV (N=515): 5 (1) | Placebo + RDV (N=518): 5 (1) |
| Coagulopathy | All subjects (N=1033): 7 (1) | Olumiant + RDV (N=515): 3 (1) | Placebo + RDV (N=518): 4 (1) |
| Summary of coexisting conditions, n/total n (%)2 | |||
| None | All subjects (N=1033): 155/994 (15.6) | Olumiant + RDV (N=515): 64/496 (12.9) | Placebo + RDV (N=518): 91/498 (18.3) |
| One | All subjects (N=1033): 270/994 (27.2) | Olumiant + RDV (N=515): 148/496 (29.8) | Placebo + RDV (N=518): 122/498 (24.5) |
| Two or more | All subjects (N=1033): 569/994 (57.2) | Olumiant + RDV (N=515): 284/496 (57.3) | Placebo + RDV (N=518): 285/498 (57.2) |
bPercentages are based on the number of subjects with data available for the individual comorbidity.
ACTT-2=Adaptive COVID-19 Treatment Trial 2; DVT=deep vein thrombosis; IQR=interquartile range; PE=pulmonary embolism; RDV=remdesivir.
SELECT IMPORTANT SAFETY INFORMATION RELATED TO TUBERCULOSIS
Evaluate patients for active infection prior to initiating Olumiant. Olumiant should not be given to patients with active TB. Monitor patients for development of signs and symptoms of TB, including patients who tested negative for latent TB prior to initiating therapy.
SELECT IMPORTANT SAFETY INFORMATION RELATED TO VIRAL REACTIVATION
Viral reactivation, including cases of herpes virus reactivation (e.g., herpes zoster), were reported in clinical trials with Olumiant. If a patient develops herpes zoster, interrupt Olumiant treatment until the episode resolves. The impact of Olumiant on chronic viral hepatitis reactivation is unknown. Screen for viral hepatitis in accordance with clinical guidelines before starting therapy with Olumiant.
COV-BARRIER Data Overview
COV-BARRIER (COVID II) Study Design
COV-BARRIER was a randomized, double-blind, placebo-controlled clinical trial of hospitalized adults with confirmed SARS-CoV-2 infection that compared treatment with Olumiant 4 mg once daily (n=764) with placebo (n=761). Olumiant was administered for 14 days or until hospital discharge, whichever came first. Patients could remain on background standard of care, as defined per local guidelines, including antimalarials, antivirals, corticosteroids, and/or azithromycin. In this study prophylaxis for venous thromboembolic event (VTE) was required for all patients unless contraindicated. The most frequently used therapies at baseline were1:
- corticosteroids (79% of patients, mostly dexamethasone)
- remdesivir (19% of patients)
Patients had to have laboratory-confirmed SARS-CoV-2 infection, at least one instance of elevation in at least one inflammatory marker (CRP, D-dimer, LDH, ferritin), and at least one of the following to be enrolled in the trial: radiographic infiltrates by imaging, SpO2 <94% on room air, evidence of active COVID infection (with clinical symptoms including any of the following: fever, vomiting, diarrhea, dry cough, tachypnea defined as respiratory rate >24 breaths/min) or requirement for supplemental oxygen. Patients requiring invasive mechanical ventilation or ECMO at baseline were enrolled in an exploratory addendum study of COV-BARRIER. These patients were not included in the main COV-BARRIER study population and were analyzed separately.1
The primary endpoint was the proportion of patients who died or progressed to non-invasive ventilation/high-flow oxygen or invasive mechanical ventilation within the first 28 days of the study. Patients who required non-invasive ventilation/high-flow oxygen at baseline needed to worsen by at least 1 point on an 8-point ordinal scale to progress.1
A key secondary endpoint was all-cause mortality by Day 28.1
CRP=C-reactive protein; ECMO=extracorporeal membrane oxygenation; LDH=lactate dehydrogenase; SpO2=oxygen saturation as measured by pulse oximetry.
Patient Characteristics for COV-BARRIER
All subjects (N=1525)
|
Olumiant + SOC (N=764)
|
Placebo + SOC (N=761)
| |
|---|---|---|---|
| Age1,4 | |||
| Years, mean (SD) | All subjects (N=1525): 57.6 (14.1) | Olumiant + SOC (N=764): 57.8 (14.3) | Placebo + SOC (N=761): 57.5 (13.8) |
| Distribution, n (%) | |||
| <65 years | All subjects (N=1033): 1026 (67.3) | Olumiant + RDV (N=515): 508 (66.5) | Placebo + RDV (N=518): 518 (68.1) |
| ≥65 years | All subjects (N=1033): 499 (32.7) | Olumiant + RDV (N=515): 256 (33.5) | Placebo + RDV (N=518): 243 (31.9) |
All subjects (N=1525)
|
Olumiant + SOC (N=764)
|
Placebo + SOC (N=761)
| |
|---|---|---|---|
| Sex, n (%)1,4 | |||
| Male | All subjects (N=1525): 963 (63.1) | Olumiant + SOC (N=764): 490 (64.1) | Placebo + SOC (N=761): 473 (62.2) |
| Female | All subjects (N=1525): 562 (36.9) | Olumiant + SOC (N=764): 274 (35.9) | Placebo + SOC (N=761): 288 (37.8) |
All subjects (N=1525)
|
Olumiant + SOC (N=764)
|
Placebo + SOC (N=761)
| |
|---|---|---|---|
| Race, n (%)1,4 | |||
| American Indian or Alaska Nativea | All subjects (N=1525): 316 (20.7) | Olumiant + SOC (N=764): 148 (19.4) | Placebo + SOC (N=761): 168 (22.1) |
| Asian | All subjects (N=1525): 174 (11.4) | Olumiant + SOC (N=764): 80 (10.5) | Placebo + SOC (N=761): 94 (12.4) |
| Black or African American | All subjects (N=1525): 75 (4.9) | Olumiant + SOC (N=764): 39 (5.1) | Placebo + SOC (N=761): 36 (4.7) |
| Native Hawaiian or other Pacific Islander | All subjects (N=1525): 5 (0.3) | Olumiant + SOC (N=764): 3 (0.4) | Placebo + SOC (N=761): 2 (0.3) |
| White | All subjects (N=1525): 920 (60.3) | Olumiant + SOC (N=764): 480 (62.8) | Placebo + SOC (N=761): 440 (57.8) |
| Multiple | All subjects (N=1525): 3 (0.2) | Olumiant + SOC (N=764): 2 (0.3) | Placebo + SOC (N=761): 1 (0.1) |
| Missing | All subjects (N=1525): 32 (2.1) | Olumiant + SOC (N=764): 12 (1.6) | Placebo + SOC (N=761): 20 (2.6) |
aIncludes participants from Mexico and Latin America.
All subjects (N=1525)
|
Olumiant + SOC (N=764)
|
Placebo + SOC (N=761)
| |
|---|---|---|---|
| Geographic region, n (%)1,4 | |||
| Europeb | All subjects (N=1525): 143 (9.4) | Olumiant + SOC (N=764): 73 (9.6) | Placebo + SOC (N=761): 70 (9.2) |
| United States including Puerto Rico | All subjects (N=1525): 320 (21.0) | Olumiant + SOC (N=764): 162 (21.2) | Placebo + SOC (N=761): 158 (20.8) |
| Rest of Worldc | All subjects (N=1525): 1062 (69.6) | Olumiant + SOC (N=764): 529 (69.2) | Placebo + SOC (N=761): 533 (70.0) |
bIncludes Germany, Italy, Spain, and the United Kingdom.
cIncludes Argentina, Brazil, India, Japan, Korea (Republic of), Mexico, and Russian Federation.
All subjects (N=1525)
|
Olumiant + SOC (N=764)
|
Placebo + SOC (N=761)
| |
|---|---|---|---|
| BMI kg/m2, mean (SD)4 | All subjects (N=1525): 30.5 (6.5) | Olumiant + SOC (N=764): 30.4 (6.4) | Placebo + SOC (N=761): 30.6 (6.6) |
All subjects (N=1518)
|
Olumiant + SOC (N=762)
|
Placebo + SOC (N=756)
| |
|---|---|---|---|
| Disease duration of symptoms prior to enrollment, n (%)4 | |||
| <7 days | All subjects (N=1518): 253 (16.7) | Olumiant + SOC (N=762): 137 (18.0) | Placebo + SOC (N=756): 116 (15.3) |
| ≥7 days | All subjects (N=1518): 1265 (83.3) | Olumiant + SOC (N=762): 625 (82.0) | Placebo + SOC (N=756): 640 (84.7) |
All subjects (N=1518)
|
Olumiant + SOC (N=762)
|
Placebo + SOC (N=756)
| |
|---|---|---|---|
| Ordinal Scale Score, n (%)1,4 | |||
| 4 | All subjects (N=1518): 186 (12.3) | Olumiant + SOC (N=762): 89 (11.7) | Placebo + SOC (N=756): 97 (12.8) |
| 5 | All subjects (N=1518): 962 (63.4) | Olumiant + SOC (N=762): 490 (64.3) | Placebo + SOC (N=756): 472 (62.4) |
| 6 | All subjects (N=1518): 370 (24.4) | Olumiant + SOC (N=762): 183 (24.0) | Placebo + SOC (N=756): 187 (24.7) |
All subjects (N=1518)
|
Olumiant + SOC (N=762)
|
Placebo + SOC (N=756)
| |
|---|---|---|---|
| Concomitant medications of interest, n (%)1,4 | |||
| Remdesivir | All subjects (N=1518): 287 (18.9) | Olumiant + SOC (N=762): 140 (18.4) | Placebo + SOC (N=756): 147 (19.4) |
| Systemic corticosteroids | All subjects (N=1518): 1204 (79.3) | Olumiant + SOC (N=762): 612 (80.3) | Placebo + SOC (N=756): 592 (78.3) |
| Dexamethasone | All subjects (N=1518): 1099/1204 (91.3) | Olumiant + SOC (N=762): 566/612 (92.5) | Placebo + SOC (N=756): 533/592 (90.0) |
All subjects (N=1525)
|
Olumiant + SOC (N=764)
|
Placebo + SOC (N=761)
| |
|---|---|---|---|
| Comorbidities at baseline, n (%)1,4 | |||
| Obesity | All subjects (N=1525): 503 (33.0) | Olumiant + SOC (N=764): 250 (32.7) | Placebo + SOC (N=761): 253 (33.2) |
| Diabetes (Type I & Type II) | All subjects (N=1525): 457 (30.0) | Olumiant + SOC (N=764): 224 (29.3) | Placebo + SOC (N=761): 233 (30.6) |
| Hypertension | All subjects (N=1525): 731 (47.9) | Olumiant + SOC (N=764): 365 (47.8) | Placebo + SOC (N=761): 366 (48.1) |
BMI=body mass index; OS=ordinal scale; SD=standard deviation; SOC=standard of care.
SELECT IMPORTANT SAFETY INFORMATION RELATED TO MORTALITY
In a large, randomized, postmarketing safety study in RA patients 50 years of age and older with at least one cardiovascular risk factor treated with another JAK inhibitor, a higher rate of all-cause mortality, including sudden cardiovascular death, was observed with the JAK inhibitor compared with TNF blockers. Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with Olumiant.
SELECT IMPORTANT SAFETY INFORMATION RELATED TO MALIGNANCY AND LYMPHOPROLIFERATIVE DISORDERS
Malignancies were observed in clinical studies with Olumiant. In RA patients treated with another JAK inhibitor, a higher rate of malignancies (excluding non-melanoma skin cancer [NMSC]) and a higher rate of lymphomas were observed in patients treated with the JAK inhibitor compared with TNF blockers. A higher rate of lung cancers and an additional increased risk of overall malignancies were observed in current or past smokers treated with the JAK inhibitor compared to those treated with TNF blockers. Consider the benefits and risks for the individual patient prior to initiating or continuing therapy in patients with Olumiant, particularly in patients with a known malignancy (other than successfully treated NMSC), patients who develop a malignancy, and patients who are current or past smokers. Periodic skin examination is recommended for patients who are at increased risk for skin cancer.
COV-BARRIER OS 7 Addendum Data Overview
COV-BARRIER OS 7 Addendum Study Design
The COV-BARRIER OS 7 addendum study was an exploratory, randomized, double-blind, placebo-controlled substudy of COV-BARRIER of hospitalized adults with confirmed SARS-CoV-2 infection requiring invasive mechanical ventilation or ECMO at baseline. All eligibility criteria were the same as the main COV-BARRIER study, with the exception that patients required invasive mechanical ventilation or ECMO to be enrolled. This substudy compared treatment with Olumiant 4 mg once daily plus standard of care (n=51) with placebo plus standard of care (n=50). All patients received standard of care in keeping with local clinical practice for COVID-19 management, which could include concomitant medications such as corticosteroids, antivirals, and other treatments. In this study prophylaxis for venous thromboembolic event (VTE) was required for all patients unless contraindicated. Olumiant was administered for 14 days or until hospital discharge, whichever occurred first.6
All endpoints in this substudy are considered exploratory. Select prespecified endpoints included all-cause mortality by Day 28 and Day 60.6
COVID-19=coronavirus disease 2019; ECMO=extracorporeal membrane oxygenation; OS=ordinal scale; SARS-CoV-2=severe acute respiratory syndrome coronavirus 2.
Patient Characteristics for COV-BARRIER OS 7 Addendum Study
All subjects (N=101)
|
Olumiant + SOC (N=51)
|
Placebo + SOC (N=50)
| |
|---|---|---|---|
| Age, mean (SD)7 | |||
| Years | All subjects (N=101): 58.6 (13.8) | Olumiant + SOC (N=51): 58.4 (12.4) | Placebo + SOC (N=50): 58.8 (15.2) |
All subjects (N=101)
|
Olumiant + SOC (N=51)
|
Placebo + SOC (N=50)
| |
|---|---|---|---|
| Sex, n (%)7 | |||
| Male | All subjects (N=101): 55 (54.5) | Olumiant + SOC (N=51): 25 (49.0) | Placebo + SOC (N=50): 30 (60.0) |
| Female | All subjects (N=101): 46 (45.5) | Olumiant + SOC (N=51): 26 (51.0) | Placebo + SOC (N=50): 20 (40.0) |
aIncludes participants from Mexico and Latin America.
All subjects (N=101)
|
Olumiant + SOC (N=51)
|
Placebo + SOC (N=50)
| |
|---|---|---|---|
| Race, n (%)7 | |||
| American Indian or Alaska Nativea | All subjects (N=101): 32 (31.7) | Olumiant + SOC (N=51): 15 (29.4) | Placebo + SOC (N=50): 17 (34.0) |
| Asian | All subjects (N=101): 1 (1.0) | Olumiant + SOC (N=51): 0 (0.0) | Placebo + SOC (N=50): 1 (2.0) |
| Black or African American | All subjects (N=101): 2 (2.0) | Olumiant + SOC (N=51): 1 (2.0) | Placebo + SOC (N=50): 1 (2.0) |
| Multiple | All subjects (N=101): 2 (2.0) | Olumiant + SOC (N=51): 2 (3.9) | Placebo + SOC (N=50): 0 (0.0) |
| White | All subjects (N=101): 62 (61.4) | Olumiant + SOC (N=51): 32 (62.7) | Placebo + SOC (N=50): 30 (60.0) |
| Missing | All subjects (N=101): 2 (2.0) | Olumiant + SOC (N=51): 1 (2.0) | Placebo + SOC (N=50): 1 (2.0) |
All subjects (N=101)
|
Olumiant + SOC (N=51)
|
Placebo + SOC (N=50)
| |
|---|---|---|---|
| Country, n (%)7 | |||
| Argentina | All subjects (N=101): 21 (20.8) | Olumiant + SOC (N=51): 12 (23.5) | Placebo + SOC (N=50): 9 (18.0) |
| Brazil | All subjects (N=101): 29 (28.7) | Olumiant + SOC (N=51): 15 (29.4) | Placebo + SOC (N=50): 14 (28.0) |
| Mexico | All subjects (N=101): 31 (30.7) | Olumiant + SOC (N=51): 14 (27.5) | Placebo + SOC (N=50): 17 (34.0) |
| United States | All subjects (N=101): 20 (19.8) | Olumiant + SOC (N=51): 10 (19.6) | Placebo + SOC (N=50): 10 (20.0) |
All subjects (N=101)
|
Olumiant + SOC (N=51)
|
Placebo + SOC (N=50)
| |
|---|---|---|---|
| BMI kg/m2, mean (SD)7 | All subjects (N=101): 33.2 (7.1) | Olumiant + SOC (N=51): 34.3 (7.8) | Placebo + SOC (N=50): 32.1 (6.3) |
All subjects (N=99)
|
Olumiant + SOC (N=51)
|
Placebo + SOC (N=48)
| |
|---|---|---|---|
| Disease duration of symptoms prior to enrollment, n (%)7 | |||
| <7 days | All subjects (N=99): 6 (6.1) | Olumiant + SOC (N=51): 2 (3.9) | Placebo + SOC (N=48): 4 (8.3) |
| ≥7 days | All subjects (N=99): 93 (93.9) | Olumiant + SOC (N=51): 49 (96.1) | Placebo + SOC (N=48): 44 (91.7) |
All subjects (N=101)
|
Olumiant + SOC (N=51)
|
Placebo + SOC (N=50)
| |
|---|---|---|---|
| Concomitant medications of interest, n (%)7 | |||
| Remdesivir use | All subjects (N=101): 2 (2.0) | Olumiant + SOC (N=51): 0 (0.0) | Placebo + SOC (N=50): 2 (4.0) |
| Corticosteroid use | All subjects (N=101): 87 (86.1) | Olumiant + SOC (N=51): 43 (84.3) | Placebo + SOC (N=50): 44 (88.0) |
All subjects (N=101)
|
Olumiant + SOC (N=51)
|
Placebo + SOC (N=50)
| |
|---|---|---|---|
| Comorbidities at baseline, n (%)7 | |||
| Obesity | All subjects (N=101): 57 (56.4) | Olumiant + SOC (N=51): 28 (54.9) | Placebo + SOC (N=50): 29 (58.0) |
| Diabetes (Type I & Type II) | All subjects (N=101): 36 (35.6) | Olumiant + SOC (N=51): 20 (39.2) | Placebo + SOC (N=50): 16 (32.0) |
| Hypertension | All subjects (N=101): 55 (54.5) | Olumiant + SOC (N=51): 31 (60.8) | Placebo + SOC (N=50): 24 (48.0) |
BMI=body mass index; OS=ordinal scale; SD=standard deviation; SOC=standard of care.
SELECT IMPORTANT SAFETY INFORMATION RELATED TO MAJOR ADVERSE CARDIOVASCULAR EVENTS
In RA patients 50 years of age and older with at least one cardiovascular risk factor treated with another JAK inhibitor, a higher rate of MACE (defined as cardiovascular death, non-fatal MI, and non-fatal stroke) was observed with the JAK inhibitor compared to those treated with TNF blockers. Patients who are current or past smokers are at additional increased risk. Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with Olumiant, particularly in patients who are current or past smokers and patients with other cardiovascular risk factors. Inform patients about the symptoms of serious cardiovascular events and the steps to take if they occur. Discontinue Olumiant in patients that have experienced a myocardial infarction or stroke.
COV-BARRIER OS 7 Addendum Study All-Cause Mortality
COV-BARRIER OS 7 Addendum Study Mortality by Day 28
The proportion of patients who died by Day 28 was 39.2% (20/51) for Olumiant compared to 58.0% (29/50) for placebo [estimated difference in Day 28 risk of mortality = -18.8% (95% CI: -36.3%, 0.6%); hazard ratio = 0.54 (95% CI: 0.31, 0.96)].1
This corresponds to a 32.4% relative reduction in mortality and a number needed to treat of 6.
This was a prespecified exploratory analysis that was not type-I error controlled; therefore, treatment differences between Olumiant and placebo cannot be regarded as statistically significant.
Kaplan-Meier Estimates of 28-Day All-Cause Mortality for Patients in OS 7 at Baseline6
A Kaplan-Meier graph of 28-day all-cause mortality for patients in ordinal scale 7 at baseline for the COV-BARRIER OS7 addendum study is shown. The figure shows a hazard ratio of 0.54 with a 95% CI of 0.31 to 0.96.
The number at risk at Day 27 represents the number of participants with available data at Day 28.
HR=hazard ratio; OS=ordinal scale; SOC=standard of care.
COV-BARRIER OS 7 Addendum Study Mortality by Day 60
Kaplan-Meier Estimates of 60-Day All-Cause Mortality for Patients in OS 7 at Baseline6
A Kaplan-Meier graph of 60-day all-cause mortality for patients in ordinal scale 7 at baseline for the COV-BARRIER OS7 addendum study is shown. The figure shows a hazard ratio of 0.56 with a 95% CI of 0.33 to 0.97.
This was a prespecified exploratory analysis that was not type-I error controlled; therefore, treatment differences between Olumiant and placebo cannot be regarded as statistically significant.
The numbers at risk at Days 27 and 59 represent the numbers of participants with available data at Days 28 and 60, respectively.
View the COV-BARRIER OS 7 Addendum Study Design
HR=hazard ratio; OS=ordinal scale; SOC=standard of care.
References
- Olumiant. Prescribing information. Lilly USA, LLC.
- Kalil AC, Patterson TF, Mehta AK, et al. Baricitinib plus remdesivir for hospitalized adults with Covid-19. N Engl J Med. 2021;384(9):795-807. doi: 10.1056/NEJMoa2031994
- Kalil AC, Patterson TF, Mehta AK, et al. Baricitinib plus remdesivir for hospitalized adults with Covid-19. N Engl J Med. 2021;384(suppl):1-55. doi:10.1056/NEJMoa2031994
- Data on File. Lilly USA, LLC. DOF-BA-US-0081.
- Marconi VC, Ramanan AV, de Bono S, et al. Efficacy and safety of baricitinib for the treatment of hospitalised adults with COVID-19 (COV-BARRIER): a randomised, double-blind, parallel-group, placebo-controlled phase 3 trial. Lancet Respir Med. 2021;9(12):1407-1418. doi: 10.1016/S2213-2600(21)00331-3
- Ely EW, Ramanan AV, Kartman CE, et al. Efficacy and safety of baricitinib plus standard of care for the treatment of critically ill hospitalised adults with COVID-19 on invasive mechanical ventilation or extracorporeal membrane oxygenation: an exploratory, randomised, placebo-controlled trial. Lancet Respir Med. Published online February 3, 2022. doi:10.1016/S2213-2600(22)00006-6
- Data on file. Lilly USA, LLC. DOF-BA-US-0082.
INDICATIONS
Alopecia Areata
Olumiant is indicated for the treatment of adult patients with severe alopecia areata.
Limitations of Use: Not recommended for use in combination with other JAK inhibitors, biologic immunomodulators, cyclosporine or other potent immunosuppressants.
Rheumatoid Arthritis
Olumiant is a Janus kinase (JAK) inhibitor indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response to one or more tumor necrosis factor (TNF) blockers.
Limitations of Use: Not recommended for use in combination with other JAK inhibitors, biologic disease-modifying antirheumatic drugs (DMARDs), or with potent immunosuppressants, such as azathioprine and cyclosporine.
COVID-19
Olumiant is a Janus kinase (JAK) inhibitor indicated for the treatment of coronavirus disease 2019 (COVID-19) in hospitalized adults requiring supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).
IMPORTANT SAFETY INFORMATION FOR OLUMIANT (baricitinib) tablets
WARNING: SERIOUS INFECTIONS, MORTALITY, MALIGNANCY, MAJOR ADVERSE CARDIOVASCULAR EVENTS, AND THROMBOSIS
SERIOUS INFECTIONS
Patients treated with Olumiant are at risk for developing serious infections that may lead to hospitalization or death. Most patients with rheumatoid arthritis (RA) who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. If a serious infection develops, interrupt Olumiant until the infection is controlled. Reported infections include:
- Active tuberculosis (TB), which may present with pulmonary or extrapulmonary disease. Olumiant should not be given to patients with active tuberculosis. Test patients, except those with COVID-19, for latent TB before initiating Olumiant and during therapy. If positive, start treatment for latent infection prior to Olumiant use.
- Invasive fungal infections, including candidiasis and pneumocystosis. Patients with invasive fungal infections may present with disseminated, rather than localized, disease.
- Bacterial, viral, and other infections due to opportunistic pathogens.
Carefully consider the risks and benefits of Olumiant prior to initiating therapy in patients with chronic or recurrent infection.
Closely monitor patients for the development of signs and symptoms of infection during and after treatment with Olumiant including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy.
The most common serious infections reported with Olumiant included pneumonia, herpes zoster, and urinary tract infection. Among opportunistic infections, tuberculosis, multidermatomal herpes zoster, esophageal candidiasis, pneumocystosis, acute histoplasmosis, cryptococcosis, cytomegalovirus, and BK virus were reported with Olumiant. Some patients have presented with disseminated rather than localized disease, and were often taking concomitant immunosuppressants such as methotrexate or corticosteroids.
Avoid use of Olumiant in patients with an active, serious infection, including localized infections. Consider the risks and benefits of treatment prior to initiating Olumiant in patients: with chronic or recurrent infection; who have been exposed to TB; with a history of a serious or an opportunistic infection; who have resided or traveled in areas of endemic tuberculosis or endemic mycoses; or with underlying conditions that may predispose them to infection.
The risks and benefits of treatment with Olumiant in COVID-19 patients with other concurrent infections should be considered.
Consider anti-TB therapy prior to initiation of Olumiant in patients with a history of latent or active TB in whom an adequate course of treatment cannot be confirmed, and for patients with a negative test for latent TB but who have risk factors for TB infection.
Viral reactivation, including cases of herpes virus reactivation (e.g., herpes zoster), were reported in clinical studies with Olumiant. If a patient develops herpes zoster, interrupt Olumiant treatment until the episode resolves. The impact of Olumiant on chronic viral hepatitis reactivation is unknown. Screen for viral hepatitis in accordance with clinical guidelines before initiating Olumiant.
MORTALITY
In a large, randomized, postmarketing safety study in RA patients 50 years of age and older with at least one cardiovascular risk factor comparing another Janus kinase (JAK) inhibitor to tumor necrosis factor (TNF) blockers, a higher rate of all-cause mortality, including sudden cardiovascular death, was observed with the JAK inhibitor.
Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with Olumiant.
MALIGNANCIES
Lymphoma and other malignancies have been observed in patients treated with Olumiant. In RA patients treated with another JAK inhibitor, a higher rate of malignancies (excluding non-melanoma skin cancer [NMSC]) was observed when compared with TNF blockers. Patients who are current or past smokers are at additional increased risk. A higher rate of lymphomas was observed in patients treated with the JAK inhibitor compared to those treated with TNF blockers. A higher rate of lung cancers and an additional increased risk of overall malignancies were observed in current or past smokers treated with the JAK inhibitor compared to those treated with TNF blockers.
Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with Olumiant, particularly in patients with a known malignancy (other than successfully treated NMSC), patients who develop a malignancy, and patients who are current or past smokers.
NMSCs have been reported in patients treated with Olumiant. Periodic skin examination is recommended for patients who are at increased risk for skin cancer.
MAJOR ADVERSE CARDIOVASCULAR EVENTS
In RA patients 50 years of age and older with at least one cardiovascular risk factor treated with another JAK inhibitor, a higher rate of major adverse cardiovascular events (MACE) (defined as cardiovascular death, myocardial infarction [MI], and stroke) was observed when compared with TNF blockers. Patients who are current or past smokers are at additional increased risk. Discontinue Olumiant in patients that have experienced a myocardial infarction or stroke.
Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with Olumiant, particularly in patients who are current or past smokers and patients with other cardiovascular risk factors. Inform patients about the symptoms of serious cardiovascular events and the steps to take if they occur.
THROMBOSIS
Thrombosis, including deep venous thrombosis (DVT) and pulmonary embolism (PE), has been observed at an increased incidence in patients treated with Olumiant compared to placebo. In addition, there were cases of arterial thrombosis. Many of these adverse events were serious and some resulted in death. In RA patients 50 years of age and older with at least one cardiovascular risk factor treated with another JAK inhibitor, a higher rate of thrombosis was observed when compared with TNF blockers. Avoid Olumiant in patients at risk. Discontinue Olumiant and promptly evaluate patients with symptoms of thrombosis.
HYPERSENSITIVITY
Reactions such as angioedema, urticaria, and rash that may reflect drug hypersensitivity have been observed in patients receiving Olumiant, including serious reactions. If a serious hypersensitivity reaction occurs, promptly discontinue Olumiant while evaluating the potential causes of the reaction.
GASTROINTESTINAL PERFORATIONS
Gastrointestinal perforations have been reported in Olumiant clinical studies. Monitor Olumiant-treated patients who may be at increased risk for gastrointestinal perforation (e.g., patients with a history of diverticulitis). Promptly evaluate patients who present with new onset abdominal symptoms for early identification of gastrointestinal perforation.
LABORATORY ABNORMALITIES
Neutropenia - Olumiant treatment was associated with an increased incidence of neutropenia (absolute neutrophil count [ANC] <1000 cells/mm3) compared to placebo. Evaluate at baseline and thereafter according to routine patient management.
In patients with RA or alopecia areata (AA), avoid initiation or interrupt Olumiant treatment in patients with an ANC <1000 cells/mm3. In patients with COVID-19, avoid initiation or interrupt Olumiant treatment in patients with an ANC <500 cells/mm3.
Lymphopenia - Absolute lymphocyte count (ALC) <500 cells/mm3 were reported in Olumiant clinical trials. Lymphocyte counts less than the lower limit of normal were associated with infection in patients treated with Olumiant, but not placebo. Evaluate at baseline and thereafter according to routine patient management.
In patients with RA or AA, avoid initiation or interrupt Olumiant treatment in patients with an ALC <500 cells/mm3. In patients with COVID-19, avoid initiation or interrupt Olumiant treatment in patients with an ALC <200 cells/mm3.
Anemia - Decreases in hemoglobin levels to <8 g/dL were reported in Olumiant clinical trials. Evaluate at baseline and thereafter according to routine patient management.
In patients with RA or AA, avoid initiation or interrupt Olumiant treatment in patients with hemoglobin <8 g/dL. In patients with COVID-19, there is limited information regarding use of Olumiant in patients with hemoglobin less than 8 g/dL.
Liver Enzyme Elevations - Olumiant treatment was associated with increased incidence of liver enzyme elevation compared to placebo. Increases of alanine transaminase (ALT) ≥5x upper limit of normal (ULN) and increases of aspartate transaminase (AST) ≥10x ULN were observed in patients in Olumiant clinical trials.
Evaluate at baseline and thereafter according to routine patient management. Promptly investigate the cause of liver enzyme elevation to identify potential cases of drug-induced liver injury. If increases in ALT or AST are observed and drug-induced liver injury is suspected, interrupt Olumiant until this diagnosis is excluded.
Lipid Elevations - Treatment with Olumiant was associated with increases in lipid parameters, including total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. Assess lipid parameters approximately 12 weeks following Olumiant initiation in patients with RA or AA. Manage patients according to clinical guidelines for the management of hyperlipidemia.
VACCINATIONS
Avoid use of live vaccines with Olumiant. Update immunizations in patients with RA or AA prior to initiating Olumiant therapy in agreement with current immunization guidelines.
ADVERSE REACTIONS
In RA trials, the most common adverse reactions (≥1%) reported with Olumiant were: upper respiratory tract infections, nausea, herpes simplex, and herpes zoster.
In COVID-19 trials, the most common adverse reactions (≥1%) reported with Olumiant were: ALT ≥3x ULN, AST ≥3x ULN, thrombocytosis (platelets >600,000 cells/mm3), creatine phosphokinase >5x ULN, neutropenia (ANC <1000 cells/mm3), DVT, PE, and urinary tract infection.
In AA trials, the most common adverse reactions (≥1%) reported with Olumiant were: upper respiratory tract infections, headache, acne, hyperlipidemia, creatine phosphokinase increase, urinary tract infections, liver enzyme elevations, folliculitis, lower respiratory tract infections, nausea, anemia, neutropenia, vulvovaginal candidiasis, abdominal pain, herpes zoster, and weight increase.
PREGNANCY AND LACTATION
Based on animal studies, Olumiant may cause fetal harm when administered during pregnancy. Advise pregnant women and women of reproductive potential of the potential risk to a fetus. Consider pregnancy planning and prevention for women of reproductive potential. Advise women not to breastfeed during treatment with Olumiant and for 4 days after the last dose.
HEPATIC AND RENAL IMPAIRMENT
Olumiant is not recommended in patients with RA or AA and severe hepatic impairment or severe renal impairment (estimated glomerular filtration rate [eGFR] <30 mL/min/1.73m2).
Olumiant should only be used in patients with COVID-19 and severe hepatic impairment if the potential benefit outweighs the potential risk. Olumiant is not recommended in patients with COVID-19 who are on dialysis, have end-stage renal disease, or with eGFR <15 mL/min/1.73m2.
Please click to access full Prescribing Information, including Boxed Warning about Serious Infections, Mortality, Malignancy, Major Adverse Cardiovascular Events, and Thrombosis, and Medication Guide.
BA HCP ISI ALL 13JUN2022