A trial designed for patients still in need2,3
BEACON (Study IV) was one of four phase 3 clinical trials evaluating the efficacy of Olumiant across the RA treatment algorithm
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. 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. The primary endpoint was the proportion of patients achieving ACR20 response at week 12.
cDMARD=conventional disease-modifying antirheumatic drug; RA=rheumatoid arthritis; TNF=tumor necrosis factor; ACR20=American College of Rheumatology 20% improvement criteria.
Olumiant demonstrated significantly greater ACR20, ACR50, and ACR70 response rates vs placebo at weeks 12 and 242-4
Statistical significance declared without control for multiple comparisons in the hierarchical testing.
ACR20 is defined as achieving a 20% improvement in tender and swollen joint counts and 20% improvement in at least 3 of the 5 remaining ACR components.5
From week 16, non-responding patients could be rescued to a higher dose which is not approved. 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.
See the BEACON clinical trial design
ACR20/50/70=American College of Rheumatology 20%/50%/70% improvement criteria; ACR=American College of Rheumatology; cDMARD=conventional disease modifying antirheumatic drug; ACR20=American College of Rheumatology 20% improvement criteria.
Percentage of patients achieving ≥30%, 50%, and 70% reduction in pain from baseline2,6
From week 16, non-responding patients could be rescued to a higher dose which is not approved.
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.
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.
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.
Olumiant demonstrated significant improvement in physical function vs placebo at week 242,3
Statistical significance declared without control for multiple comparisons in the hierarchical testing.
HAQ-DI is a patient-reported questionnaire that measures the degree of difficulty experienced in completing activities of daily living such as dressing and grooming, arising, eating, walking, hygiene, reaching and gripping.7
From week 16, non-responding patients could be rescued to a higher dose which is not approved.
Missing data were reported as modified last observation carried forward (mLOCF) except for week 12, which was reported as modified baseline observation carried forward (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 the BEACON clinical trial design
HAQ-DI=Health Assessment Questionnaire-Disability Index; LS=least squares; cDMARDs=conventional disease-modifying antirheumatic drugs.
Study IV (BEACON) clinical trial
Learn more about the Study IV (BEACON) clinical trial, including ACR response, onset of ACR20 response, HAQ-DI, and DAS28.
Olumiant Safety Profile
This Olumiant safety data set includes over 2500 patients enrolled in 6 randomized, double-blind, placebo-controlled studies (three phase 2, three phase 3) and a long-term extension study. Patients were randomized to placebo (n=1070), Olumiant 2 mg (n=479), or higher dose which is not approved (n=997).
Common adverse events2
*Includes acute sinusitis, acute tonsillitis, chronic tonsillitis, epiglottitis, laryngitis, nasopharyngitis, oropharyngeal pain, pharyngitis, pharyngotonsillitis, rhinitis, sinobronchitis, sinusitis, tonsillitis, tracheitis, and upper respiratory tract infection.
†Includes eczema herpeticum, genital herpes, herpes simplex, ophthalmic herpes simplex, and oral herpes.
Additional adverse drug reactions occurring in fewer than 1% of patients: acne.
Patients in this data set were receiving background cDMARDs.
Adverse events of special interest2
*In the 0 to 52 week exposure population, most commonly reported serious infections were pneumonia, herpes zoster, and urinary tract infection.
§Although there were no TB events reported for placebo or Olumiant 2 mg in this time period, TB events were reported in patients receiving a higher dose, which is not approved.
†Excluding TB.
‡Excluding non-melanoma skin cancer (NMSC).
Patients in this data set were receiving background cDMARDs.
Lilly is conducting long-term safety studies, including post-marketing studies, to continue to evaluate the safety of Olumiant. Certain adverse events, such as malignancy, require longer observation periods and larger patient exposure to ascertain risk.
Extended safety analyses—adverse events of special interest8-15
Extended safety analyses
The extended safety analyses of baricitinib include all patients with active RA (including nonindicated patient populations) exposed to any baricitinib dose (including non-approved doses). As of February 13, 2018, 3770 patients received baricitinib for 10,127 total PY.8 Of these, 2960 (78.5%) patients had ≥52 weeks and 2466 (65.4%) patients had ≥104 weeks of treatment with a maximum exposure of 2520 days.8 The majority of patients were exposed to a higher dose which is not approved.
*Cases of disseminated tuberculosis were also reported.
†Excludes tuberculosis.
‡Includes multidermatomal herpes zoster.
§Excluding non-melanoma skin cancer (NMSC).
Limitations of data analyses
Some patients do not qualify or choose not to enroll, and some are ineligible due to prior events, such as malignancies. Some patients discontinue from the extended study for a range of possible reasons, including AEs. Information on AEs is limited to the time that patients are taking the study drug and up to approximately 4 weeks after discontinuation; information on AEs that occur more than 4 weeks after discontinuation is often not available.
Patient numbers and total exposure vary across the extended study time points as a function of patients entering or leaving the extended study, and/or changing their dosing.
Rates are subject to change depending on the timing of the data analysis.
TB=tuberculosis; PY=patient years; RA=rheumatoid arthritis; IR per 100 PY=incidence rate per 100 patient years; DVT=deep venous thrombosis; PE=pulmonary embolism; IR=incidence rate.
Olumiant mechanism of action
Olumiant is a JAK inhibitor for the treatment of moderately to severely active RA for adult patients with an inadequate response to TNFis.
ACR=American College of Rheumatology; ACR20=American College of Rheumatology 20% improvement criteria; HAQ-DI=Health Assessment Questionnaire-Disability Index; DAS28=Disease Activity Score 28.