Drug Trials Snapshots: OLUMIANT
HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the clinical trials that supported the FDA approval of this drug, and whether there were differences among sex, race and age groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.
LIMITATIONS OF THIS SNAPSHOT:
Do not rely on Snapshots to make decisions regarding medical care. Always speak to your health provider about the risks and benefits of a drug. Refer to the OLUMIANT Package Insert for complete information.
OLUMIANT (baricitinib)
Ō-loo'-mēant
Eli Lilly and Company
Approval date: May 31, 2018
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
OLUMIANT is a drug for treatment of adult patients with rheumatoid arthritis (RA) whose disease was not well controlled using RA medications called Tumor Necrosis Factor (TNF) antagonists.
How is this drug used?
OLUMIANT is a tablet taken by mouth once daily.
What are the benefits of this drug?
In the clinical trials, a greater proportion of patients who received OLUMIANT achieved an improvement in the signs and symptoms of RA in comparison to patients who received a placebo.
What are the benefits of this drug (results of trials used to assess efficacy)?
The table below summarizes efficacy results for Trials 3 and 4 based on the Intent-to-Treat (ITT) population. Demographics of that population is presented in Table 8 under MORE INFO.
Table 2. Clinical Responsea: All Treatments Provided in Addition to Conventional Disease Modifying Drugs
| Percent of Patients | ||||
|---|---|---|---|---|
| cDMARD-IRb | TNFi-IRc | |||
| Trial 3 | Trial 4 | |||
| Placebo |
OLUMIANT 2 mg/day ∆ (95% CI)d |
Placebo |
OLUMIANT 2 mg/day ∆ (95% CI)d |
|
| N | 228 | 229 | 176 | 174 |
| % ACR 20 Responders | ||||
| Week 12 Difference from Placebo |
39% | 66% 27% (18%, 35%) |
27% | 49% 22% (12%, 32%) |
| Week 24 Difference from Placebo |
42% | 61% 19% (10%, 28%) |
27% | 45% 18% (8%, 27%) |
a Patients who were rescued or discontinued treatment were considered as non-responders in the analyses.
b conventional disease-modifying antirheumatic drug- inadequate response
c tumor necrosis factor inhibitor- inadequate response
d 95% confidence interval for the difference (∆) in response rate between OLUMIANT treatment and placebo (Trial 3, Trial 4).
Adapted from OLUMIANT Prescribing Information
Figure 4: Percent of Patients Achieving ACR20 (Trial 4)
OLUMIANT Prescribing Information
Were there any differences in how well the drug worked in clinical trials among sex, race and age?
- Sex: OLUMIANT worked similarly in men and women.
- Race: OLUMIANT worked similarly among studied races.
- Age: OLUMIANT worked similarly in patients younger and older than 65 years of age.
Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?
Figure 5 below summarizes results for the primary efficacy endpoint, ACR20, by sex, race, age and ethnicity from a combined analysis of Trials 3 and 4. The figure shows odds ratios, where an odds ratio greater than one indicates more patients responding on drug than placebo.
Figure 5. Analysis of Treatment Effect by Subgroup*
*OR = odss ratio
LCL = lower confidence limit
UCL = Upper confidence limit
M = male
F = female
Amer = American
Hisp = Hispanic
FDA Review
What are the possible side effects?
OLUMIANT may cause life threatening infections, because it can decrease the ability of the immune system to fight infections.
Other serious side effects include blood clots in the legs called thrombosis, blood clots in the lungs called embolus, cancers, and tears in the stomach and intestines.
The most common side effects of OLUMIANT are upper respiratory infections, nausea, and herpes.
What are the possible side effects (results of trials used to assess safety)?
The table below summarizes adverse reactions, in patients with rheumatoid arthritis, who received at least one dose of OLUMIANT.
Table 3. Adverse Reactions Occurring in Greater Than or Equal to 1% of OLUMIANT and Baricitinib 4 mg Treated Patients in Placebo-Controlled Trials
| Events | Weeks 0-16 | ||
|---|---|---|---|
| Placebo n=1070 (%) |
OLUMIANT 2 mg n=479 (%) |
Baricitinib 4 mg n=997 (%) |
|
| Upper respiratory tract infectionsa | 11.7 | 16.3 | 14.7 |
| Nausea | 1.6 | 2.7 | 2.8 |
| Herpes simplexb | 0.7 | 0.8 | 1.8 |
| Herpes zoster | 0.4 | 1.0 | 1.4 |
a Includes acute sinusitis, acute tonsillitis, chronic tonsillitis, epiglottitis, laryngitis, nasopharyngitis, oropharyngeal pain, pharyngitis, pharyngotonsillitis, rhinitis, sinobronchitis, sinusitis, tonsillitis, tracheitis, and upper respiratory tract infection.
b Includes eczema herpeticum, genital herpes, herpes simplex, ophthalmic herpes simplex, and oral herpes.
OLUMIANT Prescribing Information
Were there any differences in side effects among sex, race and age?
- Sex: The occurrence of side effects was similar in men and women.
- Race: The occurrence of side effects was similar among studied races.
- Age: The occurrence of side effects was similar in patients younger and older than 65 years of age.
Were there any differences in side effects of the clinical trials among sex, race, and age groups?
The tables below summarize the occurrence of treatment emergent adverse events by subgroup for the safety population.
Table 4. Pooled Analysis of Treatment Emergent Adverse Events by Sex, Race, and Age (safety population)
| Demographic Characteristic | PLACEBO n/N (%) |
OLUMIANT 2mg n/N (%) |
Baricitinib 4mg* n/N (%) |
|---|---|---|---|
| Sex | |||
| Men | 117/208) (10.9) | 53/93 (57.0) | 124/203 (61.1) |
| Women | 475/869 (55.1) | 227/386 (58.8) | 551/794 (69.4)) |
| Race | |||
| White | 412/699 (58.9) | 215/340 (63.2) | 441/672 (65.6) |
| Black or African American | 15/32 (46.9) | 10/19 (46.5) | 12/22 (54.5) |
| Asian | 144/283 (50.9) | 48/102 (47.1) | 185/244 (75.8) |
| American Indian or Native Alaskan | 11/45 (24.4) | 6/17 (35.3) | 22/42 (52.4) |
| Native Hawaiian or Other Pacific Islander | 1/1 (100.0) | 0 | 1/1 (100.0) |
| All Other | 9/10 (90.0) | 1/1 (100.0) | 14/16 (87.5) |
| Age Group | |||
| 482/897 (53.7) | 235/397 (59.2) | 535/798 (67.0) | |
| > 65 years | 110/173 (63.6) | 45/82 (54.9) | 140/199 (70.4) |
*Not approved dose
Clinical Trial Data
WHO WAS IN THE CLINICAL TRIALS?
Who participated in the clinical trials?
The FDA approved OLUMIANT based on evidence primarily from four clinical trials (Trial 1/NCT01711359, Trial 2/NCT01710358, Trial 3/NCT01721057, and Trial 4/NCT01721044) of 2456 patients with moderate to severe rheumatoid arthritis. The trials were conducted at 738 sites in Canada, Central America, Europe, Japan, South America, and the United states.
Figure 1 summarizes how many men and women were in the clinical trials used to evaluate side effects (safety population).
Figure 1. Baseline Demographics by Sex (safety population)
FDA Review
Figure 2 summarizes the percentage of patients by race in the clinical trials used to evaluate side effects (safety population).
Figure 2. Baseline Demographics by Race (safety population)
FDA Review
Table 1. Demographics of Safety Trials by Race
| Race | Number of Patients | Percentage |
|---|---|---|
| White | 1711 | 67% |
| Black or African American | 73 | 3% |
| Asian | 629 | 25% |
| American Indian or Alaska Native | 104 | 4% |
| Native Hawaiin or Other Pacific Islander | 2 | less than 1% |
| Other | 22 | 1% |
| Missing | 5 | less than 1% |
FDA Review
Figure 3 summarizes the percentage of patients by age based on the safety population.
Figure 3. Baseline Demographics by Age (safety population)
FDA Review
Who participated in the trials?
The table below summarizes demographics of all patients in the safety population.
Table 5. Demographic Characteristics of the safety Population
| Demographic Parameters | Placebo (N = 1070) n (%) |
OLUMIANT 2 mg (N = 479) n(%) |
Baricitinib 4 mg* (N= 997) n(%) |
Total (N = 2546) n(%) |
|---|---|---|---|---|
| Sex | ||||
| Men | 208 (19.4) | 93 (19.4) | 203 (20.4) | 504 (19.8) |
| Women | 862 (80.6) | 386 (80.6) | 794 (79.6) | 2042 (80.2) |
| Race | ||||
| White | 699 (65.3) | 340 (71.0) | 672 (67.4) | 1711 (67.2) |
| Black or African American | 32 (3.0) | 19 (4.0) | 22 (2.2) | 73 (2.9) |
| Asian | 283 (26.4) | 102 (21.3) | 244 (24.5) | 629 (24.7) |
| American Indian or Alaska Native | 45 (4.2) | 17 (3.5) | 42 (4.2) | 104 (4.1) |
| Native Hawaiian or Othe Pacific Islander | 1 (0.1) | 0 | 1 (0.1) | 2 (0.1) |
| Other | 9 (0.8) | 1 (0.2) | 12 1.2) | 22 (0.9) |
| Missing | 1 (0.1) | 0 | 4 (0.4) | 5 (0.2) |
| Age | ||||
| Mean years (SD) | 52.9 (11.9) | 53.2 (12.0) | 53.7 (12.0) | 53.3 (11.9) |
| Median (years) | 54 | 54 | 55 | 54 |
| Min, max (years) | 19, 83 | 21, 82 | 20, 82 | 19, 83 |
| Age Group | ||||
| 897 (83.8) | 397 (82.9) | 798 (80.0) | 2092 (82.2) | |
| > 65 years | 173 (16.2) | 82 (17.1) | 199 (20.0) | 454 (17.8) |
| Ethnicity | ||||
| Hispanic | 280 (26.2) | 93 (19.4) | 262 (26.3) | 635 (24.9) |
| Not Hispanic | 736 (68.8) | 358 (74.7) | 707 (70.9) | 1801 (70.7) |
| Missing | 54 (5.0) | 28 (5.8) | 28 (2.8) | 110 (4.3) |
| Region | ||||
| United States | 208 (19.4) | 141 (29.4) | 201 (20.2) | 550 (21.6) |
| Canada | 16 (1.5) | 14 (2.9) | 15 (1.5) | 45 (1.8) |
| Rest of the World | 846 (79.1) | 324 (67.6) | 781 (78.3) | 1951 (79.4) |
* Not approved dose
Clinical Trial Data
The table below summarizes demographics of patients, in Trial 3 and 4, used to assess efficacy. The intent to treat population is presented.
Table 6. Demographic Characteristics of the Intent-to-Treat (ITT) Population (Trials 3 and 4)
| Demographic Parameters | Placebo (N = 404) n (%) |
OLUMIANT 2 mg (N = 403) n(%) |
Baricitinib 4 mg* (N= 404) n(%) |
Total (N = 1211) n(%) |
|---|---|---|---|---|
| Sex | ||||
| Men | 70 (17.3) | 82 (20.3) | 68 (16.8) | 220 (18.2) |
| Women | 334 (82.7) | 321 (79.7) | 336 (83.2) | 991 (81.8) |
| Race | ||||
| White | 300 (74.3) | 300 (74.4) | 292 (72.3) | 892 (73.7) |
| Black or African American | 18 (4.4) | 18 (4.5) | 16 (4.0) | 52 (4.3) |
| Asian | 71 (17.6) | 70 (17.4) | 71 (17.6) | 212 (17.5) |
| American Indian or Alaska Native | 12 (3.0) | 14 (3.5) | 20 (5.00) | 46 (3.8) |
| Native Hawaiian or Othe Pacific Islander | 1 (0.2) | 0 | 0 | 1 (0.1) |
| Other | 2 (0.5) | 1 (0.2) | 1 (0.2) | 4 (0.3) |
| Missing | 0 | 0 | 4 (1.0) | 4 (0.3) |
| Age | ||||
| Mean years (SD) | 54 (12) | 54 (12) | 54 (12) | 54 (12) |
| Median (years) | 55 | 54 | 56 | 55 |
| Min, max (years) | 21, 79 | 21, 82 | 20, 82 | 20, 82 |
| Age Group | ||||
| 333 (82.4) | 335 (83.1) | 330 (81.7) | 998 (82.4) | |
| > 65 years | 71 (17.6) | 68 (16.9) | 74 (18.3) | 213 (17.6) |
| Ethnicity | ||||
| Hispanic | 97 (24.0) | 86 (21.3) | 102 (25.2) | 285 (23.5) |
| Not Hispanic | 307 (76.0) | 317 (78.7) | 302 (74.8) | 926 (76.5) |
| Region | ||||
| United States | 123 (30.4) | 125 (31.0) | 126 (31.2) | 374 (30.9) |
| Canada | 8 (2.0) | 8 (2.0) | 3 (0.7) | 19 (1.6) |
| Rest of the World | 273 (67.6) | 270 (67.0) | 275 (68.1) | 818 (67.5) |
*Not approved dose
Clinical Trial Data
How were the trials designed?
The benefit and side effects of OLUMIANT* were evaluated primarily in four clinical trials of patients with moderate to severely active rheumatoid arthritis. Each trial had a different design and/or treatment duration.
Trial 1: Trial 1 evaluated patients with rheumatoid arthritis, who had not received more than 3 doses of methotrexate, and never received drugs to slow progression of arthritis. Patients were randomly assigned to receive baricitinib 4 mg, baricitinib 4 mg plus methotrexate, or methotrexate daily for 52 weeks. Neither the patients nor the healthcare providers knew which treatment was being given until after the trial was completed. The benefit of OLUMIANT was assessed using ACR20 after 24 weeks of treatment by comparing baricitinib 4 mg alone to baricitinib 4 mg plus methotrexate and to methotrexate alone. ACR20 measures 20% improvement of arthritis. The ACR20 response is based on standardized criteria used to assess the benefit of arthritis medications on signs and symptoms of RA, such as improvement in the number of tender and swollen joints.
Trial 2: Trial 2 evaluated patients with rheumatoid arthritis who did not improve on methotrexate. Patients were randomly assigned to receive baricitinib 4 mg once daily, adalimumab (a drug that treats RA) every 2 weeks, or placebo, as additions to treatment with methotrexate, for 52 weeks. Neither the patients nor the healthcare providers knew which treatment was being given until after the trial was completed. The benefit of OLUMIANT was assessed using ACR20 after 12 weeks of treatment by comparing baricitinib 4 mg to adalimumab and placebo. From Week 16, patients that did not respond to treatment could receive baricitinib 4 mg once daily.
Trial 3: Trial 3 evaluated patients with rheumatoid arthritis, who did not improve on or tolerate drugs that slow the progression of rheumatoid arthritis. Patients were randomly assigned to receive OLUMIANT, baricitinib 4 mg, or placebo added to existing treatment with drugs that slow the progression of rheumatoid arthritis for 24 weeks. The benefit of OLUMIANT was assessed using ACR20 after 12 weeks of treatment by comparing OLUMIANT to and placebo. From Week 16, patients that did not respond to treatment could receive baricitinib 4 mg once daily.
Trial 4: Trial 4 evaluated patients with rheumatoid arthritis, who did not improve on or tolerate drugs that slow the progression of rheumatoid arthritis. Patients received OLUMIANT or baricitinib 4 mg once daily, or placebo added to treatment with drugs that slow the progression of rheumatoid arthritis for 24 weeks. The benefit of OLUMIANT was assessed using ACR20 after 12 weeks of treatment by comparing OLUMIANT to placebo. From Week 16, patients who did not respond to treatment, could receive baricitinib 4 mg once daily.
*OLUMIANT is equivalent to baricitinib 2 mg, baricitinib 4 mg is not an approved dose.
How were the trials designed?
The FDA approved OLUMIANT based on data primarily from four randomized, double-blind, multicenter trials in patients with moderate to severe active rheumatoid arthritis diagnosed according to American College of Rheumatology (ACR)/European League Against Rheumatism 2010 criteria. Patients were over 18 years of age with at least 6 tender and 6 swollen joints.
Trial 1 was a 52-week trial in patients with rheumatoid arthritis, who were naive to conventional or biologic disease-modifying antirheumatic drug (cDMARD) treatment, and had received no more than 3 doses of methotrexate. Patients received baricitinib 4 mg once daily, baricitinib 4 mg once daily plus methotrexate, or methotrexate. Methotrexate was dose-escalated over an 8-week period. From Week 24, non-responding patients were rescued to receive baricitinib 4 mg once daily plus methotrexate. The primary endpoint was the proportion of patients who achieved an ACR20 response at Week 24.
Trial 2 was a 52-week trial in patients with rheumatoid arthritis, who had an inadequate response to methotrexate. Patients received baricitinib 4 mg once daily, adalimumab 40 mg subcutaneously every 2 weeks, or placebo. All patients were on background methotrexate. From Week 16, non-responding patients could be rescued to receive baricitinib 4 mg once daily. At Week 24, all placebo-treated patients who had not been rescued were switched to receive baricitinib 4 mg once daily. The primary endpoint was the proportion of patients who achieved an ACR20 response at Week 12.
Trial 3 was a 24-week trial in patients with rheumatoid arthritis, 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. The primary endpoint was the proportion of patients who achieved an ACR20 response at Week 12.
Trial 4 was a 24-week trial in patients with rheumatoid arthritis, who had an inadequate response or intolerance to one or more tumor necrosis factor (TNF) inhibitor therapies, with or without other biologic DMARDs. Patients received OLUMIANT 2 mg, baricitinib 4 mg once daily or placebo added to background cDMARD treatment. From Week 16, non-responding patients could be rescued to receive baricitinib 4 mg once daily. The primary endpoint was the proportion of patients who achieved an ACR20 response at Week 12.
GLOSSARY
CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.
COMPARATOR: A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested.
EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.
PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.
SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.