Rheumatoid Arthritis Efficacy

A trial designed for patients still in need^1,2

BEACON (Study RA-4) was one of four phase 3 clinical trials evaluating the efficacy of Olumiant across the RA treatment algorithm^1,2

Olumiant was evaluated in a 24-week, randomized, double-blind, placebo-controlled trial in 527 patients with moderately to severely active RA who had an inadequate response or intolerance to at least 1 TNF inhibitor. Patients received Olumiant 2 mg (n=174) or baricitinib 4 mg (n=177) once daily or placebo (n=176), added to stable background cDMARD treatment.

Olumiant was evaluated in a 24-week randomized, double-blind, phase 3, placebo-controlled trial in 527 patients with moderately to severely active RA who had an inadequate response or intolerance to one or more TNF inhibitors; the patients could have had prior therapy with other biologic DMARDs.^* The patients in this study were on stable background cDMARDs.

From week 16, non-responding patients could be rescued to a higher dose (baricitinib 4 mg/day). Baricitinib 4 mg is not an approved dose for RA.

Primary endpoint

Proportion of patients achieving ACR20 response at week 12 with Olumiant 4mg + cDMARDs which is not an approved dose in RA.

Select inclusion criteria

Inadequate response or intolerance to ≥1 TNFi. The patients in the study could have had prior therapy with other biologic DMARDs
Stable background cDMARDs

Secondary measures included

ACR50 and ACR70
DAS28-CRP
HAQ-DI

^* Biologic DMARDs included TNF inhibitors (etanercept, adalimumab, infliximab, golimumab, certolizumab), non-TNF inhibitors (abatacept, tocilizumab, rituximab, anakinra), and non-approved agents.

RA=rheumatoid arthritis; TNFi=tumor necrosis factor inhibitor; DMARD=disease-modifying antirheumatic drug; cDMARD=conventional disease-modifying antirheumatic drug; ACR20/50/70=American College of Rheumatology 20%/50%/70% improvement criteria; DAS28-CRP=Disease Activity Score 28–C-reactive protein; HAQ-DI=Health Assessment Questionnaire-Disability Index.

Patient characteristics and disease activity in the BEACON trial (Study RA-4) ^2,4,5

	Placebo + cDMARDs (n=176)	Olumiant 2 mg + cDMARDs (n=174)
Mean (SD) age, years	Placebo + cDMARDs (n=176): 56 (11)	Olumiant 2 mg + cDMARDs (n=174): 55 (11)
Female	Placebo + cDMARDs (n=176): 145 (82)	Olumiant 2 mg + cDMARDs (n=174): 137 (79)
Mean (SD) duration of RA, years	Placebo + cDMARDs (n=176): 14 (10)	Olumiant 2 mg + cDMARDs (n=174): 14 (8)
ACPA positive	Placebo + cDMARDs (n=176): 125 (71)	Olumiant 2 mg + cDMARDs (n=174): 124 (71)
RF positive	Placebo + cDMARDs (n=176): 130 (74)	Olumiant 2 mg + cDMARDs (n=174): 128 (74)
No. of prior TNFi: 1	Placebo + cDMARDs (n=176): 104 (59)	Olumiant 2 mg + cDMARDs (n=174): 102 (59)
No. of prior TNFi: 2	Placebo + cDMARDs (n=176): 50 (28)	Olumiant 2 mg + cDMARDs (n=174): 60 (35)
No. of prior TNFi: ≥3	Placebo + cDMARDs (n=176): 19 (11)	Olumiant 2 mg + cDMARDs (n=174): 12 (7)
No. of prior non-TNFi: 1	Placebo + cDMARDs (n=176): 37 (21)	Olumiant 2 mg + cDMARDs (n=174): 45 (26)
No. of prior non-TNFi: 2	Placebo + cDMARDs (n=176): 15 (9)	Olumiant 2 mg + cDMARDs (n=174): 14 (8)
No. of prior non-TNFi: ≥3	Placebo + cDMARDs (n=176): 10 (6)	Olumiant 2 mg + cDMARDs (n=174): 11 (6)
No. of prior bDMARDs: 1	Placebo + cDMARDs (n=176): 81 (46)	Olumiant 2 mg + cDMARDs (n=174): 69 (40)
No. of prior bDMARDs: 2	Placebo + cDMARDs (n=176): 47 (27)	Olumiant 2 mg + cDMARDs (n=174): 55 (32)
No. of prior bDMARDs: ≥3	Placebo + cDMARDs (n=176): 47 (27)	Olumiant 2 mg + cDMARDs (n=174): 50 (29)
No. of concomitant cDMARDS: 1	Placebo + cDMARDs (n=176): 160 (91)	Olumiant 2 mg + cDMARDs (n=174): 156 (90)
No. of concomitant cDMARDS: ≥2	Placebo + cDMARDs (n=176): 16 (9)	Olumiant 2 mg + cDMARDs (n=174): 17 (10)
Concomitant MTX use	Placebo + cDMARDs (n=176): 143 (81)	Olumiant 2 mg + cDMARDs (n=174): 141 (81)
Mean (SD) MTX dose, mg/week	Placebo + cDMARDs (n=176): 16 (5)	Olumiant 2 mg + cDMARDs (n=174): 16 (5)
Concomitant corticosteroid use	Placebo + cDMARDs (n=176): 116 (66)	Olumiant 2 mg + cDMARDs (n=174): 92 (53)

Data displayed are n (%) unless otherwise noted.

959 patients were screened to randomize 527 patients in the following regions: US and Canada (44%), Europe (30%), Central and South America (10%), Asia (6%), and Rest of World (10%).

	Placebo + cDMARDs (n=176)	Olumiant 2 mg + cDMARDs (n=174)
Swollen joint count (SJC), of 66	Placebo + cDMARDs (n=176): 17 (11)	Olumiant 2 mg + cDMARDs (n=174): 19 (12)
Tender joint count (TJC), of 68	Placebo + cDMARDs (n=176): 28 (16)	Olumiant 2 mg + cDMARDs (n=174): 31 (16)
Physician Global Assessment^†	Placebo + cDMARDs (n=176): 67 (19)	Olumiant 2 mg + cDMARDs (n=174): 67 (17)
Patient Global Assessment^†	Placebo + cDMARDs (n=176): 66 (19)	Olumiant 2 mg + cDMARDs (n=174): 67 (19)
Pain^†	Placebo + cDMARDs (n=176): 65 (19)	Olumiant 2 mg + cDMARDs (n=174): 62 (22)
HAQ-DI^‡	Placebo + cDMARDs (n=176): 1.78 (0.57)	Olumiant 2 mg + cDMARDs (n=174): 1.71 (0.55)
hsCRP, mg/L^§	Placebo + cDMARDs (n=176): 21 (25)	Olumiant 2 mg + cDMARDs (n=174): 20 (22)
ESR, mm/hr	Placebo + cDMARDs (n=176): 47 (24)	Olumiant 2 mg + cDMARDs (n=174): 45 (24)
DAS28-CRP	Placebo + cDMARDs (n=176): 5.9 (0.9)	Olumiant 2 mg + cDMARDs (n=174): 6.0 (0.9)

Data displayed are mean (standard deviation).

^†Scores for the physician global assessment, patient global assessment, and pain range from 0 to 100 mm on a visual analog scale (VAS), with higher scores indicating greater levels of reported disease activity or pain.

^‡Scores on the HAQ-DI range from 0 to 3, with higher scores indicating greater disability.

^§The upper limit of normal range (ULN) for the hsCRP level is 3 mg/L.

SD=standard deviation; ACPA=anti-citrullinated peptide/protein antibody; RF=rheumatoid factor; bDMARD=biologic disease-modifying antirheumatic drug; MTX=methotrexate; hsCRP=high-sensitivity C-reactive protein. ESR = erythrocyte sedimentation rate. DAS28 = Disease Activity Score modified to include the 28-joint count. HAQ-DI = Health Assessment Questionnaire-Disability Index. ULN=upper limit of normal. ESR = Erythrocyte sedimentation rate. DAS28-CRP=Disease Activity Score 28–C-reactive protein.

Reach for results

Olumiant reduced the signs and symptoms of RA^1-3

TNFi-IR patients receiving Olumiant demonstrated higher ACR response rates vs placebo at weeks 12 and 24

Statistical significance declared without control for multiple comparisons in the hierarchical testing.

The American College of Rheumatology 20%/50%/70% improvement criteria (ACR20/50/70) response rates at weeks 12 and 24 are presented as bar graphs.

In the following results, patients taking Olumiant 2 milligrams (mg)/day plus conventional disease-modifying antirheumatic drugs (cDMARDs) (n=174) were compared to patients taking placebo plus cDMARDs (n=176).

At week 12, 49% of patients taking Olumiant 2 mg/day plus cDMARDs achieved an ACR20 response compared to 27% of patients taking placebo plus cDMARDs, with a p-value of ≤0.001. At week 12, 20% of patients taking Olumiant 2 mg/day plus cDMARDs achieved an ACR50 response compared to 8% of patients taking placebo plus cDMARDs, with a p-value of ≤0.01. At week 12, 13% of patients taking Olumiant 2 mg/day plus cDMARDs achieved an ACR70 response compared to 2% of patients taking placebo plus cDMARDs, with a p-value of ≤0.001.

At week 24, 45% of patients taking Olumiant 2 mg/day plus cDMARDs achieved an ACR20 response compared to 27% of patients taking placebo plus cDMARDs, with a p-value of ≤0.001. At week 24, 23% of patients taking Olumiant 2 mg/day plus cDMARDs achieved an ACR50 response compared to 13% of patients taking placebo plus cDMARDs, with a p-value of ≤0.05. At week 24, 13% of patients taking Olumiant 2 mg/day plus cDMARDs achieved an ACR70 response compared to 3% of patients taking placebo plus cDMARDs, with a p-value of ≤0.001.

From week 16, non-responding patients could be rescued to a higher dose which is not approved for RA. Patients who were rescued or discontinued treatment were considered non-responders in the analysis.

Primary endpoint was the proportion of patients achieving ACR20 response at week 12 with Olumiant 4mg which is not approved for RA.

See RA-BEACON trial design

SELECT IMPORTANT SAFETY INFORMATION: WARNING RELATED TO SERIOUS INFECTIONS, MORTALITY, MALIGNANCY, MAJOR ADVERSE CARDIOVASCULAR EVENTS, AND THROMBOSIS

SERIOUS INFECTIONS: Olumiant-treated patients are at increased risk of serious bacterial, fungal, viral and opportunistic infections leading to hospitalization or death, including tuberculosis (TB). Interrupt treatment with Olumiant if a serious infection occurs until the infection is controlled. Olumiant should not be given to patients with active tuberculosis. Test for latent TB before and during therapy, except for COVID-19; treat latent TB prior to use. Monitor all patients for active TB during treatment, even patients with initial negative, latent TB test.

MORTALITY: Higher rate of all-cause mortality, including sudden cardiovascular death was observed with another Janus kinase (JAK) inhibitor vs. tumor necrosis factor (TNF) blockers in rheumatoid arthritis (RA) patients.

MALIGNANCIES: Malignancies have also occurred in patients treated with Olumiant. Higher rate of lymphomas and lung cancers was observed with another JAK inhibitor vs. TNF blockers in RA patients.

MAJOR ADVERSE CARDIOVASCULAR EVENTS (MACE): Higher rate of MACE (defined as cardiovascular death, myocardial infarction, and stroke) was observed with another JAK inhibitor vs. TNF blockers in RA patients.

THROMBOSIS: Thrombosis has occurred in patients treated with Olumiant. Increased incidence of pulmonary embolism, venous and arterial thrombosis was observed with another JAK inhibitor vs. TNF blockers.

ACR20 Response Rates at Week 12 by Treatment History^1-3

Statistical significance declared without control for multiple comparisons in the hierarchical testing.

The American College of Rheumatology 20% improvement criteria (ACR20) response rates at week 12 by treatment history are presented as bar graphs.

In all patients (N=350), the percentage of patients with ACR20 response rates at week 12 in patients taking Olumiant 2 mg +cDMARDS (n=174) was 49% compared to 27% of patients taking placebo +cDMARDs (n=176). The p-value was ≤0.001.

In patients who had a treatment history of <3 biologic disease-modifying antirheumatic drug (bDMARDs) (n=253), the percentage of patients with ACR20 response rates taking Olumiant 2 mg/day plus cDMARDs was 53% compared to 33% of patients taking placebo plus cDMARDs.

In patients who had a treatment history of ≥3 bDMARDs (n=97), the percentage of patients with ACR20 response rates taking Olumiant 2 mg/day plus cDMARDs was 38% compared to 13% of patients taking placebo plus cDMARDs.

In patients who had a treatment history of one tumor necrosis factor inhibitor (TNFi) (n=206), the percentage of patients with ACR20 response rates taking Olumiant 2 mg/day plus cDMARDs was 53% compared to 30% of patients taking placebo plus cDMARDs.

In patients who had a treatment history of ≥2 TNFis (n=141), the percentage of patients with ACR20 response rates taking Olumiant 2 mg/day plus cDMARDs was 43% compared to 25% of patients taking placebo plus cDMARDs.

Patients who discontinued treatment were considered non-responders in the analysis.

The subgroup data presented were from prespecified (patients by number of prior bDMARDs) or post hoc analysis (patients by number of prior TNFis), but were not type I error controlled. Therefore, treatment differences between Olumiant and placebo for the subgroup analysis cannot be regarded as statistically significant.

Inclusion criteria for the BEACON study (Study RA-4) required inadequate response or intolerance to ≥1 TNFi.

Primary endpoint was the proportion of patients achieving ACR20 response at week 12 with Olumiant 4 mg + cDMARDs which is not an approved dose for RA.

Prior treatment experience in BEACON

40% of the patients taking Olumiant 2 mg + cDMARDs or placebo + cDMARDs in the study had prior treatment experience with ≥2 TNFis
28% of patients taking Olumiant 2 mg + cDMARDs or placebo + cDMARDs in the study had prior treatment experience with ≥3 bDMARDs

See RA-BEACON trial design

Results TNFi-IR patients can feel

Pain improvement at weeks 1, 12, and 24^1,2

Percentage of TNF-IR patients achieving ≥30%, ≥50%, and ≥70% reduction in pain from baseline

Pain Improvement Graphs — The percentages of patients with pain improvement ≥30%, ≥50%, and ≥70% at weeks 1, 12, and 24 are presented as bar graphs.

In the following results, patients taking Olumiant 2 milligrams (mg)/day plus conventional disease-modifying antirheumatic drugs (cDMARDs) (n=174) were compared to patients taking placebo plus cDMARDs (n=176).

At week 1, the percentage of patients with ≥30% pain improvement was 25% for the Olumiant 2 mg/day plus cDMARDs arm compared to 20% in the placebo plus cDMARDs arm. At week 1, the percentage of patients with ≥50% pain improvement was 9% for the Olumiant 2 mg/day plus cDMARDs arm compared to 6% in the placebo plus cDMARDs arm. At week 1, the percentage of patients with ≥70% pain improvement was 3% for the Olumiant 2 mg/day plus cDMARDs arm compared to 2% in the placebo plus cDMARDs arm.

At week 12, the percentage of patients with ≥30% pain improvement was 43% for the Olumiant 2 mg/day plus cDMARDs arm compared to 31% in the placebo plus cDMARDs arm. At week 12, the percentage of patients with ≥50% pain improvement was 31% for the Olumiant 2 mg/day plus cDMARDs arm compared to 17% in the placebo plus cDMARDs arm. At week 12, the percentage of patients with ≥70% pain improvement was 19% for the Olumiant 2 mg/day plus cDMARDs arm compared to 7% in the placebo plus cDMARDs arm.

At week 24, the percentage of patients with ≥30% pain improvement was 44% for the Olumiant 2 mg/day plus cDMARDs arm compared to 34% in the placebo plus cDMARDs arm. At week 24, the percentage of patients with ≥50% pain improvement was 32% for the Olumiant 2 mg/day plus cDMARDs arm compared to 20% in the placebo plus cDMARDs arm. At week 24, the percentage of patients with ≥70% pain improvement was 22% for the Olumiant 2 mg/day plus cDMARDs arm compared to 9% in the placebo plus cDMARDs arm.

From week 16, non-responding patients could be rescued to a higher dose which is not approved for RA.

Missing data for pain analyses, tender and swollen joint counts were reported as mLOCF.

The data presented were from a post hoc analysis of the ACR component pain (VAS, 0-100) and were not type I error controlled. Therefore treatment differences between Olumiant and placebo cannot be regarded as statistically significant.

Primary endpoint was the proportion of patients achieving ACR20 response at week 12.

In BEACON (TNFi-IR) (Olumiant 2 mg/day n=174; placebo n=176), 49% of patients receiving Olumiant + cDMARDs achieved ACR20 response at week 12 vs 27% of patients receiving placebo + cDMARDs. Patients who discontinued treatment were considered non-responders in the analysis.

For number of tender joints (0-68), the mean for placebo + cDMARD patients was 28 at baseline and 20 at week 12 and for Olumiant 2 mg + cDMARD patients the mean was 31 at baseline and 19 at week 12.

For number of swollen joints (0-66), the mean for placebo + cDMARD patients was 17 at baseline and 12 at week 12 and for Olumiant 2 mg + cDMARD patients the mean was 19 at baseline and 10 at week 12.

For pain, the mean score (VAS, 0-100) for placebo + cDMARD patients was 65 at baseline and 55 at week 12 and for Olumiant 2 mg + cDMARD patients the mean score was 62 at baseline and 46 at week 12.

See RA-BEACON trial design

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. Interrupt Olumiant if the patient develops a serious infection, an opportunistic infection, or sepsis. Do not resume Olumiant until the infection is controlled.

TNFi-IR=tumor necrosis factor inhibitor-inadequate response; mLOCF=modified last observation carried forward; cDMARD=conventional disease-modifying antirheumatic drug; ACR20=American College of Rheumatology 20% improvement criteria; VAS=visual analog scale;0=best, 100=worst.

Pain improvement at week 12 by treatment history^1,2

The percentages of patients with pain improvement at week 12 by treatment history are presented as bar graphs.

In patients who had a treatment history of 1 tumor necrosis factor inhibitor (TNFi) (n=203), the percentage of patients with ≥30% pain improvement was 45% in the Olumiant 2 mg/day plus conventional disease-modifying antirheumatic drugs (cDMARDs) arm compared to 34% in the placebo plus cDMARDs arm. In patients who had a treatment history of >1 TNFi (n=137), the percentage of patients with ≥30% pain improvement was 41% in the Olumiant 2 mg/day plus cDMARDs arm compared to 29% in the placebo plus cDMARDs arm. In patients who had a treatment history of <3 biologic disease-modifying antirheumatic drugs (bDMARDs) (n=249), the percentage of patients with ≥30% pain improvement was 47% in the Olumiant 2 mg/day plus cDMARDs arm compared to 37% in the placebo plus cDMARDs arm. In patients who had a treatment history of ≥3 bDMARDs (n=94), the percentage of patients with ≥30% pain improvement was 34% in the Olumiant 2 mg/day plus cDMARDs arm compared to 16% in the placebo plus cDMARDs arm.

In patients who had a treatment history of 1 TNFi (n=203), the percentage of patients with ≥50% pain improvement was 32% in the Olumiant 2 mg/day plus cDMARDs arm compared to 21% in the placebo plus cDMARDs arm. In patients who had a treatment history of >1 TNFi (n=137), the percentage of patients with ≥50% pain improvement was 30% in the Olumiant 2 mg/day plus cDMARDs arm compared to 12% in the placebo plus cDMARDs arm. In patients who had a treatment history of <3 bDMARDs (n=249), the percentage of patients with ≥50% pain improvement was 36% in the Olumiant 2 mg/day plus cDMARDs arm compared to 21% in the placebo plus cDMARDs arm. In patients who had a treatment history of ≥3 bDMARDs (n=94), the percentage of patients with ≥50% pain improvement was 20% in the Olumiant 2 mg/day plus cDMARDs arm compared to 7% in the placebo plus cDMARDs arm.

In patients who had a treatment history of 1 TNFi (n=203), the percentage of patients with ≥70% pain improvement was 21% in the Olumiant 2 mg/day plus cDMARDs arm compared to 8% in the placebo plus cDMARDs arm. In patients who had a treatment history of >1 TNFi (n=137), the percentage of patients with ≥70% pain improvement was 16% in the Olumiant 2 mg/day plus cDMARDs arm compared to 6% in the placebo plus cDMARDs arm. In patients who had a treatment history of <3 bDMARDs (n=249), the percentage of patients with ≥70% pain improvement was 22% in the Olumiant 2 mg/day plus cDMARDs arm compared to 8% in the placebo plus cDMARDs arm. In patients who had a treatment history of ≥3 bDMARDs (n=94), the percentage of patients with ≥70% pain improvement was 10% in the Olumiant 2 mg/day plus cDMARDs arm compared to 5% in the placebo plus cDMARDs arm.

Missing data for pain analyses, tender and swollen joint counts were reported as mLOCF.

The data presented were from a post hoc analysis of the ACR component pain (VAS 0-100). The BEACON study was not powered for these subgroups analyses, nor were the analyses type I error controlled. Therefore, treatment differences between Olumiant and placebo, observed in these subgroups, cannot be regarded as statistically significant.

Inclusion criteria for the BEACON study required inadequate response or intolerance to ≥1 TNFi.

Primary endpoint was the proportion of patients achieving ACR20 response at week 12 with Olumiant 4 mg + cDMARDs which is not an approved dose for RA.

In BEACON (TNFi-IR) (Olumiant 2 mg/day n=174; placebo n=176), 49% of patients receiving Olumiant + cDMARDs achieved ACR20 response at week 12 vs 27% of patients receiving placebo + cDMARDs. Patients who discontinued treatment were considered non-responders in the analysis.

For pain, the mean score (VAS, 0-100) for placebo + cDMARD patients was 65 at baseline and 55 at week 12 and for Olumiant 2 mg + cDMARD patients the mean score was 62 at baseline and 46 at week 12.

For number of tender joints (0-68), the mean for placebo + cDMARD patients was 28 at baseline and 20 at week 12 and for Olumiant 2 mg + cDMARD patients the mean was 31 at baseline and 19 at week 12.

For number of swollen joints (0-66), the mean for placebo + cDMARD patients was 17 at baseline and 12 at week 12 and for Olumiant 2 mg + cDMARD patients the mean was 19 at baseline and 10 at week 12.

See RA-BEACON trial design

Improved physical function may be within reach with Olumiant^1,2

Differences in HAQ-DI improvement between Olumiant vs placebo were significant at week 24

Change in HAQ-DI Graph — A line graph representing change in HAQ-DI in the placebo plus cDMARD arm (n=176) and the Olumiant 2 mg/day plus cDMARD arm (n=174) is shown. In the figure, the Y-axis represents the LS mean change from baseline in HAQ-DI score, and the X-axis represents the timepoint in weeks. Data points on the placebo plus cDMARD line include 0 at week 0, -0.09 at week 1, -0.16 at week 2, -0.18 at week 4, -0.21 at week 8, -0.17 at week 12, -0.17 at week 14, -0.17 at week 16, -0.16 at week 20, and -0.15 at week 24. Data points on the Olumiant 2 mg/day plus cDMARD line include 0 at week 0, -0.18 at week 1, -0.21 at week 2, -0.3 at week 4, -0.36 at week 8, -0.37 at week 12, -0.38 at week 14, -0.42 at week 16, -0.4 at week 20, and -0.37 at week 24. Nominal p-values are indicated at weeks 1, 4, 8, 12, 14, 16, and 20. A p-value ≤0.001 is indicated at week 24.

From week 16, non-responding patients could be rescued to a higher dose which is not approved for RA.

Missing data were reported as mLOCF except for week 12, which was reported as mBOCF.

Primary endpoint was the proportion of patients achieving ACR20 response at week 12.

Mean baseline HAQ-DI was 1.71 for Olumiant 2 mg +cDMARDs and 1.78 for placebo +cDMARDs.

See RA-BEACON trial design

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.

HAQ-DI=Health Assessment Questionnaire-Disability Index; cDMARD=conventional disease-modifying antirheumatic drug; LS=least squares; ACR20=American College of Rheumatology 20% improvement criteria; mLOCF=modified last observation carried forward; mBOCF=modified baseline observation carried forward.

Help TNFi-IR patients achieve low disease activity^1,2

Percentage of patients achieving DAS28 <2.6 and ≤3.2 at weeks 12 and 24^1,2

DAS28 results graph — The percentages of patients with a Disease Activity Score-28 (DAS28) of <2.6 and ≤3.2 at weeks 12 and 24 are presented as bar graphs.

In the following results, patients taking Olumiant 2 milligrams (mg)/day plus conventional disease-modifying antirheumatic drugs (cDMARDs) (n=174) were compared to patients taking placebo plus cDMARDs (n=176).

At week 12, 11% of patients taking Olumiant 2 mg/day plus cDMARDs achieved a DAS28 score of <2.6 compared to 4% of patients taking placebo plus cDMARDs, with a p-value of ≤0.05. At week 12, the percentage of patients with a DAS28 score of ≤3.2 was 24% for the Olumiant 2 mg/day plus cDMARDs arm compared to 9% in the placebo plus cDMARDs arm.

At week 24, the percentage of patients with a DAS28 score of <2.6 was 11% for the Olumiant 2mg/day plus cDMARDs arm compared to 6% in the placebo plus cDMARDs arm. At week 24, the percentage of patients with a DAS28 score of ≤3.2 was 20% for the Olumiant 2 mg/day plus cDMARDs arm compared to 11% in the placebo plus cDMARDs arm.

From week 16, non-responding patients could be rescued to a higher dose, which is not approved for RA. Patients who were rescued or discontinued treatment were considered non-responders in the analysis.

DAS28 ≤3.2 presented were from a prespecified analysis, but were not type I error controlled. Therefore treatment differences between Olumiant and placebo cannot be regarded as statistically significant.

Primary endpoint was the proportion of patients achieving ACR20 response at week 12.

See RA-BEACON trial design

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.

TNFi-IR=tumor necrosis factor inhibitor-inadequate response; DAS28=Disease Activity Score-28; cDMARD=conventional disease-modifying antirheumatic drug; ACR20=American College of Rheumatology 20% improvement criteria. RA=rheumatoid arthritis.

ACR responses for Olumiant and placebo in cDMARD-IR patients¹

BUILD ACR20/50/70 response rates — The American College of Rheumatology 20%/50%/70% improvement criteria (ACR20/50/70) response rates at weeks 12 and 24 are presented as bar graphs.

In the following results, patients taking Olumiant 2 milligrams (mg)/day plus conventional disease-modifying antirheumatic drugs (cDMARDs) (n=229) were compared to patients taking placebo plus cDMARDs (n=228).

At week 12, the percentage of patients with ACR20 response was 66% in the Olumiant 2 mg/day plus cDMARDs arm compared to 39% in the placebo plus cDMARDs arm. At week 12, percentage of patients with ACR50 response was 34% in the Olumiant 2 mg/day plus cDMARDs arm compared to 13% in the placebo plus cDMARDs arm. At week 12, the percentage of patients with ACR70 response was 18% in the Olumiant 2mg/day plus cDMARDs arm compared to 3% in the placebo plus cDMARDs arm.

At week 24, the percentage of patients with ACR20 response was 61% in the Olumiant 2 mg/day plus cDMARDs arm compared to 42% in the placebo plus cDMARDs arm. At week 24, percentage of patients with ACR50 response was 41% in the Olumiant 2 mg/day plus cDMARDs arm compared to 21% in the placebo plus cDMARDs arm. At week 24, the percentage of patients with ACR70 response was 25% in the Olumiant 2mg/day plus cDMARDs arm compared to 8% in the placebo plus cDMARDs arm.

Olumiant is not indicated for cDMARD-IR patients.

Patients who were rescued or discontinued treatment were considered non-responders in the analysis.

BUILD (Study RA-3) was a 24 -week trial in 684 patients with moderately to severely active RA who had an inadequate response or intolerance to cDMARDs. Patients received Olumiant 2 mg or baricitinib 4 mg once daily or placebo added to existing background cDMARD treatment. From week 16, non-responding patients could be rescued to receive baricitinib 4 mg once daily. Baricitinib 4 mg is not an approved dose for RA. Primary endpoint was the proportion of patients achieving ACR20 response at week 12.

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.

cDMARD-IR=conventional disease-modifying antirheumatic drug-inadequate response.

Components of ACR Response at week 12¹

BUILD ACR Components at week 12 — The components of the American College of Rheumatology (ACR) response at week 12 in conventional disease-modifying antirheumatic drug-inadequate response (cDMARD-IR) patients are presented as bar graphs.

In the following results, patients taking Olumiant 2 milligrams (mg)/day plus conventional disease-modifying antirheumatic drugs (cDMARDs) (n=229) were compared to patients taking placebo plus cDMARDs (n=228).

For the number of tender joints (0-68), the mean baseline number was 24 in the Olumiant 2 mg/day plus cDMARDs arm with a change from baseline of -13 and the mean baseline number was 24 in the placebo plus cDMARDs arm with a change from baseline of -9.

For the number of swollen joints (0-66), the mean baseline number was 14 in the Olumiant 2 mg/day plus cDMARDs arm with a change from baseline of -9 and the mean baseline number was 13 in the placebo plus cDMARDs arm with a change from baseline of -5.

For pain, the mean baseline score was 60 in the Olumiant 2 mg/day plus cDMARDs arm with a change from baseline of -26 and the mean baseline score was 57 in the placebo plus cDMARDs arm with a change from baseline of -14.

For patient global assessment, the mean baseline score was 62 in the Olumiant 2 mg/day plus cDMARDs arm with a change from baseline of -26 and the mean baseline score was 60 in the placebo plus cDMARDs arm with a change from baseline of -16.

For physician global assessment, the mean baseline score was 64 in the Olumiant 2 mg/day plus cDMARDs arm with a change from baseline of -31 and the mean baseline score was 62 in the placebo plus cDMARDs arm with a change from baseline of -21.

For Health Assessment Questionnaire-Disability Index (HAQ-DI), the mean baseline score was 1.51 in the Olumiant 2 mg/day plus cDMARDs arm with a change from baseline of -0.55 and the mean baseline score was 1.50 in the placebo plus cDMARDs arm with a change from baseline of -0.33.

For high-sensitivity C-reactive protein (hsCRP) (mg/L), the mean baseline number was 18.2 in the Olumiant 2 mg/day plus cDMARDs arm with a change from baseline of -9.6 and the mean baseline number was 17.7 in the placebo plus cDMARDs arm with a change from baseline of -0.5.

Olumiant is not indicated for cDMARD-IR patients.

A modified last observation carried forward (mLOCF) was used for missing data and patients who discontinued treatment.

Data shown are mean.

Primary endpoint was the proportion of patients achieving ACR20 response at week 12 with Olumiant 4 mg which is not approved for RA.

^aVisual analog scale: 0=best, 100=worst.

^bHealth Assessment Questionnaire-Disability Index: 0=best, 3=worst; 20 questions; 8 categories: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and activities.

See RA-BUILD trial design

cDMARD-IR=conventional disease-modifying antirheumatic drug-inadequate response.

References

Olumiant. Prescribing Information. Lilly USA, LLC. Eli Lilly and Company; 2022.
Genovese MC, Kremer J, Zamani O, et al. Baricitinib in patients with refractory rheumatoid arthritis. N Engl J Med. 2016;374:1243-1252.
Genovese MC, Kremer J, Kartman C, et al. Previous biologic disease-modifying antirheumatic drug exposure and efficacy and safety analysis from a phase 3 study of baricitinib in patients with rheumatoid arthritis and an inadequate response to tumor necrosis factor inhibitors. Poster presented at: ACR Annual; 2015; San Francisco, CA.
Smolen JS, Kremer JM, Gaich CL, et al. Patient-reported outcomes from a randomised phase III study of baricitinib in patients with rheumatoid arthritis and an inadequate response to biological agents (RA-BEACON). Ann Rheum Dis. 2017;0:1-7.
Genovese MC, Kremer J, Zamani O, et al. Baricitinib in patients with refractory rheumatoid arthritis. N Engl J Med. 2016;374(suppl):1-30.
Genovese MC, Kremer JM, Kartman CE, et al. Response to baricitinib based on prior biologic use in patients with refractory rheumatoid arthritis. Rheumatology (Oxford). 2018;57:900-908.
Taylor P, Zhu B, Gaich C, et al. SAT0055 Baricitinib showed rapid and greater reduction in pain compared to adalimumab or placebo in patients with rheumatoid arthritis. Ann Rheum Dis. 2017;76:788.
Pope JE, Quebe A, Zhu B, et al. Assessment of pain relief with baricitinib by treatment history in patients with refractory rheumatoid arthritis [abstract]. Arthritis Rheumatol. 2018;70(suppl 10).

Rheumatoid Arthritis Efficacy

A trial designed for patients still in need^1,2

BEACON (Study RA-4) was one of four phase 3 clinical trials evaluating the efficacy of Olumiant across the RA treatment algorithm^1,2

Patient characteristics and disease activity in the BEACON trial (Study RA-4) ^2,4,5

Olumiant reduced the signs and symptoms of RA^1-3

TNFi-IR patients receiving Olumiant demonstrated higher ACR response rates vs placebo at weeks 12 and 24

ACR20 Response Rates at Week 12 by Treatment History^1-3

Reach for results starting at week 1^1,2

Olumiant demonstrated rapid improvement, with ACR20 responses seen as early as week 1 in TNFi-IR patients

Efficacy across all ACR components^1-3

Pain improvement at weeks 1, 12, and 24^1,2

Percentage of TNF-IR patients achieving ≥30%, ≥50%, and ≥70% reduction in pain from baseline

Pain improvement at week 12 by treatment history^1,2

Improved physical function may be within reach with Olumiant^1,2

Differences in HAQ-DI improvement between Olumiant vs placebo were significant at week 24

Percentage of patients achieving MCID in HAQ-DI at weeks 12 and 24^1-3

Help TNFi-IR patients achieve low disease activity^1,2

Percentage of patients achieving DAS28 <2.6 and ≤3.2 at weeks 12 and 24^1,2

Olumiant reduced disease activity as early as 1 week¹

Olumiant patients experienced changes in disease activity as early as week 1 and through week 24¹

ACR responses for Olumiant and placebo in cDMARD-IR patients¹

Components of ACR Response at week 12¹

Disease activity in cDMARD-IR patients¹

IMPORTANT SAFETY INFORMATION

WARNINGS:

INDICATIONS

Rheumatoid Arthritis Efficacy

A trial designed for patients still in need1,2

BEACON (Study RA-4) was one of four phase 3 clinical trials evaluating the efficacy of Olumiant across the RA treatment algorithm1,2

Patient characteristics and disease activity in the BEACON trial (Study RA-4) 2,4,5

Olumiant reduced the signs and symptoms of RA1-3

TNFi-IR patients receiving Olumiant demonstrated higher ACR response rates vs placebo at weeks 12 and 24

ACR20 Response Rates at Week 12 by Treatment History1-3

Reach for results starting at week 11,2

Olumiant demonstrated rapid improvement, with ACR20 responses seen as early as week 1 in TNFi-IR patients

Efficacy across all ACR components1-3

Pain improvement at weeks 1, 12, and 241,2

Percentage of TNF-IR patients achieving ≥30%, ≥50%, and ≥70% reduction in pain from baseline

Pain improvement at week 12 by treatment history1,2

Improved physical function may be within reach with Olumiant1,2

Differences in HAQ-DI improvement between Olumiant vs placebo were significant at week 24

Percentage of patients achieving MCID in HAQ-DI at weeks 12 and 241-3

Help TNFi-IR patients achieve low disease activity1,2

Percentage of patients achieving DAS28 <2.6 and ≤3.2 at weeks 12 and 241,2

Olumiant reduced disease activity as early as 1 week1

Olumiant patients experienced changes in disease activity as early as week 1 and through week 241

ACR responses for Olumiant and placebo in cDMARD-IR patients1

Components of ACR Response at week 121

Disease activity in cDMARD-IR patients1

IMPORTANT SAFETY INFORMATION

WARNINGS:

INDICATIONS

A trial designed for patients still in need^1,2

BEACON (Study RA-4) was one of four phase 3 clinical trials evaluating the efficacy of Olumiant across the RA treatment algorithm^1,2

Patient characteristics and disease activity in the BEACON trial (Study RA-4) ^2,4,5

Olumiant reduced the signs and symptoms of RA^1-3

ACR20 Response Rates at Week 12 by Treatment History^1-3

Reach for results starting at week 1^1,2

Efficacy across all ACR components^1-3

Pain improvement at weeks 1, 12, and 24^1,2

Pain improvement at week 12 by treatment history^1,2

Improved physical function may be within reach with Olumiant^1,2

Percentage of patients achieving MCID in HAQ-DI at weeks 12 and 24^1-3

Help TNFi-IR patients achieve low disease activity^1,2

Percentage of patients achieving DAS28 <2.6 and ≤3.2 at weeks 12 and 24^1,2

Olumiant reduced disease activity as early as 1 week¹

Olumiant patients experienced changes in disease activity as early as week 1 and through week 24¹

ACR responses for Olumiant and placebo in cDMARD-IR patients¹

Components of ACR Response at week 12¹

Disease activity in cDMARD-IR patients¹