Efficacy

Olumiant was studied as monotherapy in two phase 3 trials for adults with severe alopecia areata^3,4

The primary endpoint was the proportion of patients achieving a SALT score ≤20 at week 36

BRAVE-AA1 and BRAVE-AA2 Clinical Trial Design^*

BRAVE-AA1 Study Design — Olumiant was studied in 2 clinical trials. BRAVE-AA1 was a phase 2/3 trial that enrolled 654 patients in the phase 3 portion. BRAVE-AA2 was a phase 3 trial that enrolled 546 patients. Patients were randomized 2:2:3 to placebo, Olumiant 2 mg, or Olumiant 4 mg once daily. The primary endpoint was the proportion of patients achieving a SALT score ≤20 at week 36.

^*BRAVE-AA1 was a phase 2/3 clinical trial and BRAVE-AA2 was a phase 3 clinical trial. Patient population shown for BRAVE-AA1 is for the phase 3 portion only.

Olumiant was studied in adults with SALT score ≥50 and a current alopecia areata (AA) episode lasting >6 months and <8 years in duration.

Select inclusion criteria

Males (18 to 60 years of age) and females (18 to 70 years of age)
No spontaneous improvement over the past 6 months
Patients with severe AA lasting ≥8 years were eligible only if episodes of regrowth were observed on affected areas over the past 8 years

SALT=Severity of Alopecia Tool.

Patients in the clinical trials had severe alopecia areata, with a mean scalp hair loss of 85% at baseline³

	Placebo (n=345)	Olumiant 2 mg/day (n=340)	Olumiant 4 mg/day (n=515)
Age (years), mean (SD)	Placebo (n=345): 37 (13)	Olumiant 2 mg/day (n=340): 38 (13)	Olumiant 4 mg/day (n=515): 37 (13)
Female	Placebo (n=345): 60%	Olumiant 2 mg/day (n=340): 62%	Olumiant 4 mg/day (n=515): 60%
Race
White	Placebo (n=345): 49%	Olumiant 2 mg/day (n=340): 55%	Olumiant 4 mg/day (n=515): 52%
Asian	Placebo (n=345): 38%	Olumiant 2 mg/day (n=340): 37%	Olumiant 4 mg/day (n=515): 35%
Black or African descent	Placebo (n=345): 10%	Olumiant 2 mg/day (n=340): 6%	Olumiant 4 mg/day (n=515): 9%
Duration since AA onset (years), mean (SD)	Placebo (n=345): 12 (11)	Olumiant 2 mg/day (n=340): 13 (11)	Olumiant 4 mg/day (n=515): 12 (11)
Duration of current AA episode (years), mean (SD)	Placebo (n=345): 4 (5)	Olumiant 2 mg/day (n=340): 4 (5)	Olumiant 4 mg/day (n=515): 4 (3)
<4 years	Placebo (n=345): 66%	Olumiant 2 mg/day (n=340): 68%	Olumiant 4 mg/day (n=515): 64%
≥4 years	Placebo (n=345): 34%	Olumiant 2 mg/day (n=340): 32%	Olumiant 4 mg/day (n=515): 36%
Patients with universalis	Placebo (n=345): 41%	Olumiant 2 mg/day (n=340): 45%	Olumiant 4 mg/day (n=515): 46%
Patients with atopic background^*	Placebo (n=345): 41%	Olumiant 2 mg/day (n=340): 38%	Olumiant 4 mg/day (n=515): 36%
SALT score, mean (SD)	Placebo (n=345): 85 (18)	Olumiant 2 mg/day (n=340): 86 (18)	Olumiant 4 mg/day (n=515): 85 (18)

DOSING INFORMATION

The recommended dosage is 2 mg/day. Increase to 4 mg/day if response is not adequate. For patients with nearly complete or complete scalp hair loss, with or without substantial eyelash or eyebrow hair loss, consider 4 mg/day. Decrease to 2 mg/day once patients achieve an adequate response with 4 mg/day.

For adults with severe alopecia areata

Complete or near-complete hair regrowth (≤20) by week 36 and continued through week 52^1-7*

Some patients achieved a SALT score ≤20 as early as week 16^†

BRAVE-AA1: Percentage of Patients Who Achieved a SALT Score ≤20 Through Week 52, NRI^a

BRAVE-AA1 SALT score ≤20 results through week 52 — In BRAVE-AA1, 7%, 11%, 22%, 21% of patients on Olumiant 2 mg/day (N=184), and 19%, 27%, 35%, 41% of patients on Olumiant 4 mg/day (N=281), at weeks 16, 24, 36, and 52 respectively, achieved a SALT score ≤20 versus 4%, 5%, and 5% of patients on placebo (N=189) at weeks 16, 24, and 36 (p≤0.05 for Olumiant 4 mg at week 16 vs placebo and for both doses vs placebo at weeks 24 and 36). The placebo-controlled period ended at week 36.

BRAVE-AA2: Percentage of Patients Who Achieved a SALT Score ≤20 Through Week 52, NRI^a

BRAVE-AA Trials Pooled Results: Median SALT scores were 3 (4 mg/day) and 7 (2 mg/day) among patients who achieved SALT score ≤20 at week 52 (N=296; median baseline SALT score=83)

^*Primary endpoint was the proportion of patients achieving a SALT score ≤20 at week 36 compared to placebo. These analyses at week 52 included patients randomized to Olumiant 2 mg/day or 4 mg/day at baseline who remained on their same dose.

In pooled BRAVE-AA trials, SALT score 0 was achieved by week 36 for 3.7% (n=11) of patients on Olumiant 2 mg/day, and 10% (n=46) of patients on Olumiant 4 mg/day, and by week 52 for 6.3% (n=18) of patients on Olumiant 2 mg/day, and 16% (n=70) of patients on Olumiant 4 mg/day.

^†In BRAVE-AA1, statistical significance was seen at week 16 in the 4 mg/day arm, but not in the other treatment arms; statistical conclusions cannot be made.

^aData collected after permanent study drug discontinuation or at remote visits due to the COVID-19 pandemic were excluded.

^bp≤0.05 vs placebo.

See Study Designs

Understanding SALT Scores

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. Test patients for latent TB and if positive, treat with standard antimycobacterial therapy before initiating Olumiant. Monitor patients for development of signs and symptoms of TB, including patients who tested negative for latent TB prior to initiating therapy.

NRI=nonresponder imputation; SALT=Severity of Alopecia Tool.

For adults with severe alopecia areata

With Olumiant 4 mg/day, an improvement in eyebrow and eyelash coverage was observed at week 36^1,2,4,10-12*

Results shown for patients with substantial eyebrow and eyelash hair loss at baseline

EB and EL ClinRO for eyelash and eyebrow hair regrowth at 36 weeks — In BRAVE-AA1, 31% of patients on Olumiant 4 mg/day (N=188) achieved EB ClinRO 0,1 with ≥2-point improvement from baseline at week 36 vs 3% on placebo (N=124) (p≤0.05). In BRAVE-AA2, 35% of patients on Olumiant 4 mg/day (N=161) achieved EB ClinRO 0,1 with ≥2-point improvement from baseline at week 36 vs 4% on placebo (N=112) (p≤0.05).

In BRAVE-AA1, 34% of patients on Olumiant 4 mg/day (N=167) achieved EL ClinRO 0,1 with ≥2-point improvement from baseline at week 36 vs 3% on placebo (N=96) (p≤0.05). In BRAVE-AA2, 34% of patients on Olumiant 4 mg/day (N=140) achieved EL ClinRO 0,1 with ≥2-point improvement from baseline at week 36 vs 6% on placebo (N=90) (p≤0.05).

All analyses were NRI.

^*The EB ClinRO and EL ClinRO are 4-point scales measuring eyebrow and eyelash hair loss, respectively, ranging from 0 (EB ClinRO: Full eyebrow coverage and no areas of eyebrow hair loss; EL ClinRO: Continuous eyelash line along both eyelids) to 3 (EB ClinRO: No notable eyebrow; EL ClinRO: No notable eyelashes). The ClinRO measures were developed following psychometric validation techniques but with limited data on content validity and interrater reliability. Both eyebrows and both eyelashes were evaluated together, not individually. This information should be taken into consideration when evaluating these data.

^†Data collected after permanent study drug discontinuation or at remote visits due to the COVID-19 pandemic were excluded.

^‡p≤0.05 vs placebo.

See Study Designs

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.

ClinRO Measure for Eyebrow Hair Loss™ and ClinRO Measure for Eyelash Hair Loss™ are trademarks owned or licensed by Eli Lilly and Company, its subsidiaries or affiliates.

EB ClinRO=Clinician-Reported Outcome Measure for Eyebrow Hair Loss™; EL ClinRO=Clinician-Reported Outcome Measure for Eyelash Hair Loss™; NRI=nonresponder imputation.

For adults with severe alopecia areata

An improvement in eyebrow and eyelash coverage was observed through 52 weeks with Olumiant 4 mg/day¹³

More patients had an observed improvement in eyebrow and eyelash coverage from week 36 through 52¹³

BRAVE-AA1 and BRAVE-AA2 (Pooled analysis): Percentage of patients with a ClinRO^* measure for EB hair loss 0,1 with ≥2-point improvement from Week 0 through 52, NRI^13†

Clinician reported outcome for eyebrow through week 52 — Results were pooled for study participants treated with Olumiant 4 mg/day (N=349) from 0 to 52 weeks in the BRAVE clinical trial program. The percentage of patients with a ClinRO measure for eyebrow hair loss equal to zero or one, with a two or greater improvement, at the primary endpoint of week 36 was 33%. After the long term extension at week 52 it was 44%. All analyses were NRI.

BRAVE-AA1 and BRAVE-AA2 (Pooled analysis): Percentage of patients with a ClinRO^* measure for EL hair loss 0,1 with ≥2-point improvement from Week 0 through 52, NRI¹³

Clinician reported outcome for eyelash through week 52 — Results were pooled for study participants treated with Olumiant 4 mg/day (N=307) from 0 to 52 weeks in the BRAVE clinical trial program. The percentage of patients with a ClinRO measure for eyelash hair loss equal to zero or one, with a two or greater improvement, at the primary endpoint of week 36 was 34%. After the long term extension at week 52 it was 45%. All analyses were NRI.

In patients receiving treatment with 4 mg/day, decrease the dosage to 2 mg/day once patients achieve an adequate response.¹

The long-term extension data (Week 36-52) of BRAVE-AA trials were not placebo controlled.^15,16

ClinRO Measure for Eyebrow Hair Loss^™ and ClinRO Measure for Eyelash Hair Loss^™ are trademarks owned or licensed by Eli Lilly and Company, its subsidiaries or affiliates.

ClinRO=Clinician-Reported Outcomes, EB=eyebrows, EL=eyelashes, NRI=nonresponder imputation, SALT=Severity of Alopecia Tool.

See Study Designs

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.

For adults with severe alopecia areata

Visible results with Olumiant through week 36^1,17-19

See the difference Olumiant can make

Scalp Hair Results

Patient 1

Scalp photos of alopecia areata patient at baseline and at week 36

Clinical trial patient treated with Olumiant 2 mg/day for 36 weeks. Individual results may vary.^*

Patient 2

Clinical trial patient treated with Olumiant 4 mg/day for 36 weeks. Individual results may vary.^*

Patient 3

Clinical trial patient treated with Olumiant 2 mg/day for 36 weeks. Individual results may vary.^*

Patient 4

Clinical trial patient treated with Olumiant 4 mg/day for 36 weeks. Individual results may vary.^*

Patient hairstyles may influence appearance of SALT scores depicted.

^*Based on the pooled post-hoc, placebo-controlled analysis of patients who achieved the primary endpoint (SALT score ≤20 at week 36) in BRAVE-AA trials, the observed mean SALT score at week 36 was 8.6 (SD: 6.7) among patients treated with Olumiant 2 mg/day (N=67) and the observed mean SALT score at week 36 was 6.4 (SD: 6.5) among patients treated with Olumiant 4 mg/day (N=175).¹⁸

See Study Designs

Understanding SALT Scores

Eyebrow and Eyelash Results

Eyebrow photos of alopecia areata patient at baseline and at week 36

Eyelash photos of alopecia areata patient at baseline and at week 36

Clinical trial patients treated with Olumiant 4 mg/day for 36 weeks. Individual results may vary.

The ClinRO measures were developed following psychometric validation techniques but with limited data on content validity and interrater reliability. Both eyebrows and both eyelashes were evaluated together, not individually. This information should be taken into consideration when evaluating these data.¹⁰

Explore Efficacy Data

See Study Designs

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.

EB ClinRO=Clinician-Reported Outcome Measure for Eyebrow Hair Loss^™; EL ClinRO=Clinician-Reported Outcome Measure for Eyelash Hair Loss^™; SALT=Severity of Alopecia Tool; SD=standard deviation.

For adults with severe alopecia areata

Long-term extension study design: Responders (SALT score ≤20) at week 52 were eligible for re-randomization^15*

BRAVE-AA1 and BRAVE-AA2: Long-Term Extension Study Design^15-17

BRAVE-AA1 and BRAVE-AA2: Long-Term Extension Study Design graphic

^*Sub-study eligible responders (SALT score ≤20) were re-randomized. Patients randomized to placebo at baseline, rescued to Olumiant at week 36, and had a SALT score ≤20 at week 52 were not eligible for re-randomization.^15,16,20
^†In BRAVE-AA2, patients randomized to Olumiant 2 mg QD at baseline and had a SALT score ≤20 at week 52 remained on their same dose.

PBO=placebo, SALT=Severity of Alopecia Tool.

SELECT IMPORTANT SAFETY INFORMATION RELATED TO THROMBOSIS Thrombosis, including deep venous thrombosis (DVT) and pulmonary embolism (PE), was observed at an increased incidence in Olumiant-treated patients compared to patients treated with placebo. Arterial thrombosis events in the extremities have also reported in clinical studies with Olumiant. 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, higher rates of overall thrombosis, DVT, and PE were observed compared to those treated with TNF blockers. If clinical features of DVT/PE or arterial thrombosis occur, discontinue Olumiant and promptly evaluate and appropriately treat patients. Avoid Olumiant in patients that may be at increased risk for thrombosis.

Explore 36 Week Efficacy Data

See Study Designs

For adults with severe alopecia areata

3-year sustained response rates^3,14-16,20*

Among patients on Olumiant who achieved a SALT score ≤20 at 1 year, most sustained ≥80% scalp coverage through 3 years

BRAVE-AA Trials (Pooled Results): Percentage of Responders Who Sustained a SALT Score ≤20 Through Week 152, LOCF^a

BRAVE-EE Trials Chart with percentage of responders who sustained a SALT Score <=20 through week 152. Olumiant 2mg and 4mg. — BRAVE-AA1 and BRAVE-AA2 (Pooled Results): 84% of responders on Olumiant 2mg/day (N=67) and 89% of responders on Olumiant 4mg/day (N=129) sustained a SALT score ≤20 from week 52 to week 152.

Study Design: In the BRAVE-AA trials, patients randomized to Olumiant 4 mg or 2 mg remained on treatment until week 52. At week 52, responders (SALT score ≤20; N=278) were re-randomized to either: treatment continuation (both trials), withdrawal to placebo (BRAVE-AA1) or down-titration from 4 mg to 2 mg (BRAVE-AA2).

Down-Titration Efficacy: In BRAVE-AA2, 59% of patients (N=42) on Olumiant who achieved a SALT score ≤20 at week 52 sustained ≥80% scalp coverage through week 152 when their dose was reduced from Olumiant 4mg/day to 2mg/day.

^*,aLOCF analysis excludes study drug discontinuation or dose change after week 52.

The long-term extension data of BRAVE-AA trials were not placebo controlled.

LOCF=last observation carried forward; SALT=Severity of Alopecia Tool.

SELECT IMPORTANT SAFETY INFORMATION RELATED TO 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.

For adults with severe alopecia areata

BRAVE-AA1: Among patients on Olumiant who achieved a SALT score ≤20 at week 52, few sustained a SALT score ≤20 after discontinuing treatment^21*

BRAVE-AA1: Percentage of Responders Who Sustained a SALT Score ≤20 From Week 52 to Week 104 After Discontinuing Treatment, MI+NRI^a

SALT Score ≤20 After Discontinuing Treatment, 20% and 10% for Olumiant 4mg/day and 2mg/day — BRAVE-AA1: 10% of responders who switched from 2 mg/day to placebo (N=10) and 20% of responders who switched from 4 mg/day to placebo (N=30) sustained a SALT score ≤20 from week 52 to week 104.

*^,aMI+NRI analysis excludes data after permanent study drug discontinuation, treatment switch after week 52 visit, or collected at remote visits due to the COVID-19 pandemic. Missing data due to COVID-19 were imputed by MI; data missing for other reasons were imputed as nonresponse.

These analyses included BRAVE-AA1 responders (SALT score ≤20) at week 52 who were randomized from Olumiant 2 mg/day and Olumiant 4 mg/day to placebo withdrawal.

The study population sample size should be taken into consideration when evaluating these data.

See BRAVE-AA1 and BRAVE-AA2 Long-Term Extension trial design

MI=multiple imputation; NRI=nonresponder imputation; SALT=Severity of Alopecia Tool.

SELECT IMPORTANT SAFETY INFORMATION RELATED TO GASTROINTESTINAL PERFORATIONS
Gastrointestinal perforations have been reported in Olumiant clinical trials. Monitor Olumiant-treated patients who may be at increased risk for gastrointestinal perforation (e.g., patients with a history of diverticulitis). Promptly evaluate patients presenting with new onset abdominal symptoms for early identification of gastrointestinal perforation.

Evaluate ANC, ALC, hemoglobin, and liver enzymes at baseline and thereafter according to routine patient management.

Dose Titration Results

For adults with severe alopecia areata

SALT score ≤20 response rate after decreasing the treatment dose for responders

Among patients on Olumiant who achieved a SALT score ≤20 at 1 year, over half sustained ≥80% scalp coverage through year 3, after their dose was lowered^1,22,23

BRAVE-AA2 Down-Titration Period (Weeks 52-152): Percentage of Responders Who Sustained a SALT Score ≤20, LOCF^*

Chart of BRAVE-AA2 Down-Titration Period (Weeks 52-104): Percentage of Responders Who Sustained a SALT Score ≤20 — BRAVE-AA2 (Weeks 52-152): 59% of responders (N=42) sustained a SALT score ≤20 when their dose was reduced from Olumiant 4 mg/day to 2 mg/day.

In patients receiving treatment with 4 mg/day, decrease the dosage to 2 mg/day once patients achieve an adequate response.

Patients randomized to Olumiant 4 mg or 2 mg remained on treatment until week 52, and then responders (SALT score ≤20) on Olumiant 4 mg (N=85) either continued treatment or down-titrated to 2 mg.

*LOCF excludes study drug discontinuation or dose change after week 52.

The long-term extension data of BRAVE-AA2 were not placebo controlled.

LOCF=last observation carried forward; SALT=Severity of Alopecia Tool.

SELECT IMPORTANT SAFETY INFORMATION RELATED TO LABORATORY ABNORMALITIES
In clinical trials, Olumiant treatment was associated with:

Neutropenia: Avoid Olumiant initiation or interrupt Olumiant treatment in patients with absolute neutrophil count (ANC) <1000 cells/mm³.
Lymphopenia: Avoid Olumiant initiation or interrupt treatment in patients with absolute lymphocyte count (ALC) <500 cells/mm³.
Anemia: Avoid Olumiant initiation or interrupt treatment in patients with hemoglobin <8 g/dL.
Liver enzyme elevations: Promptly investigate cause of liver enzyme elevations. If alanine transaminase (ALT) or aspartate transaminase (AST) is increased and drug-induced liver injury is suspected, interrupt Olumiant until this diagnosis is excluded.
Lipid elevations: Assess lipid parameters approximately 12 weeks after initiating Olumiant and follow clinical guidelines for the management of hyperlipidemia.

Evaluate ANC, ALC, hemoglobin, and liver enzymes at baseline and thereafter according to routine patient management.

References:

Olumiant. Prescribing Information. Lilly USA, LLC.
King B, Ohyama M, Kwon O, et al. Two phase 3 trials of baricitinib for alopecia areata. N Engl J Med. 2022;386:1687-1699. doi:10.1056/NEJMoa2110343.
Data on file. Lilly USA, LLC. DOF-BA-US-0075.
King B, Ohyama M, Kwon O, et al. Two phase 3 trials of baricitinib for alopecia areata. N Engl J Med. 2022;386(suppl):1-76.
Data on file. Lilly USA, LLC. DOF-BA-US-0074.
Data on file. Lilly USA, LLC. DOF-BA-US-0076.
Data on file. Lilly USA, LLC. DOF-BA-US-0122.
Data on file. Lilly USA, LLC. DOF-BA-US-0070.
Data on file. Lilly USA, LLC. DOF-BA-US-0117.
Wyrwich K, Kitchen H, Knight S, et al. Development of clinician-reported outcome (ClinRO) and patient-reported outcome (PRO) measures for eyebrow, eyelash and nail assessment in alopecia areata. Am J Clin Dermatol. 2020;21(5):725-732.
Data on file. Lilly USA, LLC. DOF-BA-US-0063.
Data on file. Lilly USA, LLC. DOF-BA-US-0064.
Data on file. Lilly USA, LLC. DOF-BA-US-0104.
Data on file. Lilly USA, LLC. DOF-BA-US-0111.
Data on file. Lilly USA, LLC. DOF-BA-US-0078.
Data on file. Lilly USA, LLC. DOF-BA-US-0090.
Data on file. Lilly USA, LLC. DOF-BA-US-0084.
Data on file. Lilly USA, LLC. DOF-BA-US-0086.
Data on file. Lilly USA, LLC. DOF-BA-US-009.
Data on file. Lilly USA, LLC. DOF-BA-US-0105.
Data on file. Lilly USA, LLC. DOF-BA-US-0100.
Olsen EA, Hordinsky MK, Price VH, et al. Alopecia areata investigational assessment guidelines-part II. J Am Acad Dermatol. 2004;51(3):440-447.
Data on file. Lilly USA, LLC. DOF-BA-US-0065.
Data on file. Lilly USA, LLC. DOF-BA-US-0102.
King BA, Mesinkovska NA, Craiglow B, et al. Development of the alopecia areata scale for clinical use: Results of an academic-industry collaborative effort. J Am Acad Dermatol. 2022;86(2):359-364. doi:10.1016/j.jaad.2021.08.043.

IMPORTANT SAFETY INFORMATION

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, fatigue, lower respiratory tract infections, nausea, genital Candida infections, anemia, neutropenia, 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.

BA HCP ISI ALL 14SEP2022

Please click to access full Prescribing Information, including Boxed Warning about Serious Infections, Mortality, Malignancy, Major Adverse Cardiovascular Events, and Thrombosis, and Medication Guide.

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).

Efficacy

Olumiant was studied as monotherapy in two phase 3 trials for adults with severe alopecia areata^3,4

Patients in the clinical trials had severe alopecia areata, with a mean scalp hair loss of 85% at baseline³

Complete or near-complete hair regrowth (≤20) by week 36 and continued through week 52^1-7*

Some patients achieved a SALT score ≤20 as early as week 16^†

SALT Score ≤20 response rates were higher in patients with a baseline SALT score of 50-94 vs 95-100^1,8

Earlier treatment with Olumiant (AA episode ≥4 years) resulted in more patients achieving ≥80% scalp hair coverage^1,9

An improvement in eyebrow and eyelash coverage was observed through 52 weeks with Olumiant 4 mg/day¹³

Long-term extension study design: Responders (SALT score ≤20) at week 52 were eligible for re-randomization^15*

3-year sustained response rates^3,14-16,20*

BRAVE-AA1: Among patients on Olumiant who achieved a SALT score ≤20 at week 52, few sustained a SALT score ≤20 after discontinuing treatment^21*

SALT score ≤20 response rates after increasing the treatment dose for responders²⁴

The Severity of Alopecia Tool (SALT) is used to measure scalp hair loss in alopecia areata^22,23

The Alopecia Areata Scale (AASc) is a multidimensional tool for assessing severity of AA²⁵

IMPORTANT SAFETY INFORMATION

WARNING:

MORTALITY

MALIGNANCIES

MAJOR ADVERSE CARDIOVASCULAR EVENTS

THROMBOSIS

HYPERSENSITIVITY

GASTROINTESTINAL PERFORATIONS

LABORATORY ABNORMALITIES

VACCINATIONS

ADVERSE REACTIONS

PREGNANCY AND LACTATION

HEPATIC AND RENAL IMPAIRMENT

INDICATIONS

Efficacy

Olumiant was studied as monotherapy in two phase 3 trials for adults with severe alopecia areata3,4

Patients in the clinical trials had severe alopecia areata, with a mean scalp hair loss of 85% at baseline3

Expand accordion Patient baseline characteristics

Complete or near-complete hair regrowth (≤20) by week 36 and continued through week 521-7*

Some patients achieved a SALT score ≤20 as early as week 16†

SALT Score ≤20 response rates were higher in patients with a baseline SALT score of 50-94 vs 95-1001,8

Earlier treatment with Olumiant (AA episode ≥4 years) resulted in more patients achieving ≥80% scalp hair coverage1,9

An improvement in eyebrow and eyelash coverage was observed through 52 weeks with Olumiant 4 mg/day13

Long-term extension study design: Responders (SALT score ≤20) at week 52 were eligible for re-randomization15*

3-year sustained response rates3,14-16,20*

BRAVE-AA1: Among patients on Olumiant who achieved a SALT score ≤20 at week 52, few sustained a SALT score ≤20 after discontinuing treatment21*

SALT score ≤20 response rates after increasing the treatment dose for responders24

The Severity of Alopecia Tool (SALT) is used to measure scalp hair loss in alopecia areata22,23

The Alopecia Areata Scale (AASc) is a multidimensional tool for assessing severity of AA25

IMPORTANT SAFETY INFORMATION

WARNING:

MORTALITY

MALIGNANCIES

MAJOR ADVERSE CARDIOVASCULAR EVENTS

THROMBOSIS

HYPERSENSITIVITY

GASTROINTESTINAL PERFORATIONS

LABORATORY ABNORMALITIES

VACCINATIONS

ADVERSE REACTIONS

PREGNANCY AND LACTATION

HEPATIC AND RENAL IMPAIRMENT

INDICATIONS

Olumiant was studied as monotherapy in two phase 3 trials for adults with severe alopecia areata^3,4

Patients in the clinical trials had severe alopecia areata, with a mean scalp hair loss of 85% at baseline³

Complete or near-complete hair regrowth (≤20) by week 36 and continued through week 52^1-7*

Some patients achieved a SALT score ≤20 as early as week 16^†

SALT Score ≤20 response rates were higher in patients with a baseline SALT score of 50-94 vs 95-100^1,8

Earlier treatment with Olumiant (AA episode ≥4 years) resulted in more patients achieving ≥80% scalp hair coverage^1,9

An improvement in eyebrow and eyelash coverage was observed through 52 weeks with Olumiant 4 mg/day¹³

Long-term extension study design: Responders (SALT score ≤20) at week 52 were eligible for re-randomization^15*

3-year sustained response rates^3,14-16,20*

BRAVE-AA1: Among patients on Olumiant who achieved a SALT score ≤20 at week 52, few sustained a SALT score ≤20 after discontinuing treatment^21*

SALT score ≤20 response rates after increasing the treatment dose for responders²⁴

The Severity of Alopecia Tool (SALT) is used to measure scalp hair loss in alopecia areata^22,23

The Alopecia Areata Scale (AASc) is a multidimensional tool for assessing severity of AA²⁵