Baricitinib

This information is provided in response to your request. Resources may contain information about doses, uses, formulations and populations different from product labeling. See Prescribing Information above, if applicable.

Did patients who received Olumiant® (baricitinib) for the treatment of COVID-19 have changes in lymphocyte or neutrophil counts?

There were significantly more patients randomized to baricitinib who experienced any grade increase in lymphocytes and neutrophils compared to those randomized to placebo. There was no difference in leukocytes.

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US_cFAQ_BAR123G_LYMPHOCYTE_NEUTROPHIL_ABNORMALITIES_COVID-19
en-US

See important safety information, including boxed warning, in the attached prescribing information.

Olumiant Prescribing Information

Evaluate baseline complete blood count to verify whether treatment can be initiated. Monitor complete blood counts during treatment and modify dosage as recommended.1

Dose modifications for patients with coronavirus disease 2019 (COVID-19) and cytopenias are described in Dosage Modifications for Cytopenias in Patients with COVID-19.1

Dosage Modifications for Cytopenias in Patients with COVID-191

Laboratory Analyte

Laboratory Analyte Value

Recommendation

ALC

≥200 cells/µL

  • Maintain dosage

<200 cells/µL

  • Interrupt baricitinib until ALC is ≥200 cells/µL

ANC

≥500 cells/µL

  • Maintain dosage

<500 cells/µL

  • Interrupt baricitinib until ANC is ≥500 cells/µL

Abbreviations: ALC = absolute lymphocyte count; ANC = absolute neutrophil count.

Notes: If a laboratory abnormality is likely due to the underlying disease state, consider the risks and benefits of continuing baricitinib at the same or a reduced dose.

There is limited information regarding use of baricitinib in patients with COVID-19 and absolute neutrophil count (ANC) <1000 cells/mm3 or  absolute lymphocyte count (ALC) <200 cells/mm31

Baricitinib Available Clinical Data

Risk of Lymphocyte and Neutrophil Count Abnormalities in Patients With COVID-19

In patients with COVID-19

  • white blood cell (WBC) abnormalities are common with the majority of patients developing lymphocytopenia2-4
  • disease severity appears to correlate with the amount of deviation from normal in WBC counts, with more severely ill patients experiencing more leukopenia and lymphocytopenia, and 2,4-6
  • an elevated neutrophil-to-lymphocyte ratio (NLR) has been associated with more severe disease.2,7-9

Additionally, corticosteroid therapy has been used in critically ill patients with COVID-19 and has been shown to cause lymphocytopenia.2

Summary of Baricitinib Exposure Across Clinical Trial Program

Integrated Safety Dataset Exposure

In placebo-controlled COVID-19 clinical trials, ACTT-2 and COV-BARRIER, a total of

  • 1307 patients received at least one dose of baricitinib 4 mg once daily (8.1 days mean exposure, 1515 total patient-weeks of exposure), and
  • 1310 patients received placebo (8.2 days mean exposure, 1530 total patient-weeks of exposure).1,10

Patients received treatment for up to 14 days or hospital discharge, whichever occurred first. Safety data is through study day 29.1

Brief Study Design and Exposure From COV-BARRIER

COV-BARRIER is a phase 3, global, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of baricitinib in adult patients hospitalized due to COVID-19.11

In COV-BARRIER, a total of 1525 patients were randomized with either

  • baricitinib 4 mg orally once daily + standard of care (SOC) (n=764), or 
  • placebo + SOC (n=761).11

Brief Study Design and Exposure From ACTT-2

Eli Lilly and Company entered into an agreement with the National Institute of Allergy and Infectious Diseases (NIAID) part of the National Institutes of Health (NIH), to study baricitinib as an arm in NIAID’s Adaptive COVID-19 Treatment Trial 2 (ACTT-2).12

This randomized, double-blind, placebo-controlled study investigated the efficacy and safety of baricitinib plus remdesivir in hospitalized adult patients with COVID-19. Study site locations were in North America as well as Europe and Asia.12

In ACTT-2, a total of 1033 were randomized with either

  • baricitinib 4 mg + remdesivir (n=515), or 
  • placebo + remdesivir (n=518).12

Incidence of Lymphocyte and Neutrophil Abnormalities

Integrated Dataset Shift Tables

Shift Table of Lymphocyte and Neutrophil Count Abnormalities by Treatment Arm in the Integrated Safety Analysis of COV-BARRIER and ACTT-2 shows changes in Common Terminology Criteria for Adverse Events (CTCAE) grades of lymphocytes and neutrophils for each treatment arm in the integrated safety analysis of COV-BARRIER and ACTT-2. 

Shift Table of Lymphocyte and Neutrophil Count Abnormalities by Treatment Arm in the Integrated Safety Analysis of COV-BARRIER and ACTT-21,10

Change in Analyte Count, n/NAR (%)

Leukocytes

Neutrophils

Lymphocytes

PBO (N=1310)

BARI (N=1307)

PBO (N=1310)

BARI 4 mg  (N=1307)

PBO (N=1310)

BARI (N=1307)

Any CTCAE grade increase

89/1238 (7.2)

108/1250 (8.6)

90/1213 (7.4)

143/1207 (11.8)a

357/1236 (28.9)

265/1242 (21.3)a

Increase to ≥ grade 1

78/1115 (7.0)

98/1149 (8.5)

82/1154 (7.1)

134/1174 (11.4)a

165/547 (30.2)

114/494 (23.1)b

Increase to ≥ grade 2

32/1207 (2.7)

35/1228 (2.9)

40/1196 (3.3)

65/1200 (5.4)c

195/828 (23.6)

145/800 (18.1)d

Increase to ≥ grade 3

14/1232 (1.1)

10/1247 (0.8)

22/1211 (1.8)

26/1205 (2.2)

137/1113 (12.3)

96/1112 (8.6)d

Increase to ≥ grade 4

7/1238 (0.6)

4/1250 (0.3)

7/1213 (0.6)

2/1207 (0.2)

38/1236 (3.1)

25/1242 (2.0)

Abbreviations: ACTT-2 = Adaptive COVID-19 Treatment Trial 2; BARI = baricitinib; CTCAE = Common Terminology Criteria for Adverse Events; NAR = number at risk; PBO = placebo.

Note: NAR is the number of patients at risk for the specified abnormality in each treatment group. Shifts are as assessed by measured values within the clinical trial database. Frequencies are based on shifts from pre-treatment to post-treatment (with number at risk as the denominator).  

ap=.001 vs PBO.

bp=.009 vs PBO

cp=.013 vs PBO.

dp=.005 vs PBO

COV-BARRIER

In COV-BARRIER, the percentage of patients with reported lymphocyte and neutrophil count abnormalities were similar between treatment groups (Lymphocyte and Neutrophil Count Abnormalities by Treatment Arm in COV-BARRIER).10

Lymphocyte and Neutrophil Count Abnormalities by Treatment Arm in COV-BARRIER10

Preferred Term

PBO
(N=752), n (%)

BARI
(N=750), n (%)

Lymphocyte count decreased

1 (0.1)

0

Lymphopenia

4 (0.5)

1 (0.1)

Lymphocytosis

0

0

Neutrophil count decreased

0

0

Neutropenia

1 (0.1)

1 (0.1)

White blood cell count decreased

0

0

Leukopenia

2 (0.3)

3 (0.4)

Leukocytosis

11 (1.5)

9 (1.2)

 Abbreviations: BARI = baricitinib; PBO = placebo.  

ACTT-2

Incidence of Lymphocyte, Neutrophil, and Leukocyte Abnormalities

The number of patients who had treatment interrupted due to the stopping criteria for total white count, ANC <500, and ALC <200 was not specifically collected per protocol, and is not currently available. NIAID has indicated they will be able to provide reasons for treatment interruption when reported by the investigator.10

Leukocyte, lymphocyte, and neutrophil abnormalities that were reported in ACTT-2 are presented in Lymphocyte and Neutrophil Count Abnormalities by Treatment Arm in ACTT-2.

Lymphocyte and Neutrophil Count Abnormalities by Treatment Arm in ACTT-212

Preferred Terma

PBO + RDV
N=509, n (%)

BARI + RDV
N=508, n (%)

Lymphocyte count decreased

35 (6.9)b

24 (4.7)c

Lymphopenia

24 (4.7)d

11 (2.2)

Lymphocytosis

1 (0.2)

0

Neutrophil count decreased

0

1 (0.2)

Neutropenia

2 (0.4)d

1 (0.2)

White blood cell count decreased

1 (0.2)

0

Leukopenia

1 (0.2)

1 (0.2)

Leukocytosis

0

2 (0.4)

Abbreviations: ACTT-2 = Adaptive COVID-19 Treatment Trial 2; AE = adverse event; BARI = baricitinib; PBO = placebo; DAIDS = Division of AIDS; RDV = remdesivir.

aOnly grade 3 and grade 4 AEs based on DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events were captured during the study due to the severity of COVID-19 disease.

b5 of these events were reported as related to study treatment by the investigator.

c6 of these events were reported a related to study treatment by the investigator.

d1 of these events was reported as related to study treatment by the investigator.

Change in Lymphocyte and Neutrophil Count Values Among Evaluable Patients in ACTT-2

A summary of absolute baseline lymphocyte and neutrophil count values and change from baseline on day 29 lymphocyte and neutrophil count values are presented in  Absolute Baseline and Change from Baseline on Day 29 Lymphocyte and Neutrophil Count Values for the Treated Population in ACTT-2

 Absolute Baseline and Change from Baseline on Day 29 Lymphocyte and Neutrophil Count Values for the Treated Population in ACTT-210

Parameter

Baseline (absolute value)

Change from Baseline to Day 29

BARI + RDV

PBO + RDV

BARI + RDV

PBO + RDV

Na

Mean (SD)

Median (min-max)

Na

Mean (SD)

Median (min-max)

Na

Mean (SD)

Median (min-max)

Na

Mean (SD)

Median (min-max)

Basophils (109/L)

498

0.020 (0.058)

0.01
(0-1.00)

506

0.017 (0.032)

0.01
(0-0.30)

257

0.022 (0.045)

0.01
(-0.20-0.24)

250

0.036 (0.092)

0.02
(-0.20-1.00)

Eosinophils (109/L)

499

0.042 (0.157)

0
(0-3.00)

506

0.051 (0.182)

0
(0-3.20)

257

0.192 (0.171)

0.17 
(-0.30-0.95)

251

0.205 (0.267)

0.17
(-1.00-2.00)

Leukocytes (109/L)

503

7.698 (3.634)

6.80
(1.70-31.00)

508

7.455 (3.622)

6.72
(1.70-28.30)

260

-0.364 (4.532)

-0.06 (-24.20-28.00)

254

0.712 (4.176)

0.40 
(-15.30-19.40)

Lymphocytes (109/L)

499

1.316 (2.292)

1.00
(0.20-37.00)

508

1.310 (3.003)

1.03
(0-64.70)

257

0.653 (1.293)

0.70 (-13.00-2.72)

253

0.927 (1.996)

0.74
(-1.38-30.00)

Monocytes (109/L)

499

0.537 (0.898)

0.40
(0-13.40)

508

0.510 (0.686)

0.40
(0-10.70)

257

0.108 (0.434)

0.11
(-4.00-3.13)

253

0.212 (0.745)

0.14
(-3.20-9.00)

Neutrophils (109/L)

499

6.822 (8.354)

5.20
(1.10-94.60)

508

5.887 (5.019)

4.96
(1.00-86.00)

257

-1.708 (6.735)

-1.09 (-82.00-24.38)

253

-0.656 (4.205)

-0.50 (-37.00-14.40)

Abbreviations: ACTT-2 = Adaptive COVID-19 Treatment Trial 2; BARI = baricitinib; max = maximum; min = minimum; PBO = placebo; RDV = remdesivir; SD = standard deviation.

aNumber of subjects in the as treated population with laboratory data available for the parameter at the specified study visit.

Incidence of Lymphocyte and Neutrophil Count Abnormalities in Patients on Concomitant Corticosteroids in ACTT-2

In ACTT-2, systemic corticosteroid use was a non-randomized and non-standardized intervention utilized by approximately 20% of patients.13

Non-serious lymphocyte and neutrophil count reported abnormalities by treatment arm according to corticosteroid use are presented in Non-serious Lymphocyte and Neutrophil Count Abnormalities by Treatment Arm According to Corticosteroid Use in ACTT-2.

Non-serious Lymphocyte and Neutrophil Count Abnormalities by Treatment Arm According to Corticosteroid Use in ACTT-210

MedDRA Preferred Term

Corticosteroid Use After Enrollment 

No Corticosteroid Use After Enrollment 

BARI + RDV 
(N=105), n (%)

PBO + RDV
(N=118), n (%)

BARI + RDV
(N=402), n (%)

PBO + RDV
(N=391), n (%)

Lymphopenia

9 (8.6)

12 (10.2)

2 (0.5)

11 (2.8)

Neutropenia

0

0

1 (0.2)

2 (0.5)

Leukocytosis

1 (1.0)

0

1 (0.2)

0

Leukopenia

0

0

0

1 (0.3)

Lymphocytosis

0

0

0

1 (0.3)

Abbreviations: ACTT-2 = Adaptive COVID-19 Treatment Trial 2; BARI = baricitinib; MedDRA = Medical Dictionary for Regulatory Activities; PBO = placebo; RDV = remdesivir.

References

The published references below are available by contacting 1-800-LillyRx (1-800-545-5979).

1Olumiant [package insert]. Indianapolis, IN: Eli Lilly and Company; 2022.

2Slomka A, Kowalewski M, Zekanowska E. Coronavirus Disease 2019 (COVID-19): A short review on hematological manifestations. Pathogens. 2020;9(6):493. https://doi.org/10.3390/pathogens9060493

3Rawson TM, Moore LSP, Zhu N, et al. Bacterial and fungal coinfection in individuals with coronavirus: a rapid review to support COVID-19 antimicrobial prescribing. Clin Infect Dis. 2020;71(9):2459-2468. https://doi.org/10.1093/cid/ciaa530

4Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497-506. https://doi.org/10.1016/s0140-6736(20)30183-5

5Guan WJ, Ni ZY, Hu Y, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382(18):1708-1720. https://doi.org/10.1056/nejmoa2002032

6Liu K, Fang YY, Deng Y, et al. Clinical characteristics of novel coronavirus cases in tertiary hospitals in Hubei Province. Chin Med J (Engl.). 2020;133:1025–1031. https://doi.org/10.1097/CM9.0000000000000744

7Liu J, Liu Y, Xiang P, et al. Neutrophil-to-lymphocyte ratio predicts critical illness patients with 2019 coronavirus disease in the early stage. J Transl Med. 2020;18(1):206. https://doi.org/10.1186/s12967-020-02374-0

8Yang AP, Liu JP, Tao WQ, Li HM. The diagnostic and predictive role of NLR, d-NLR and PLR in COVID-19 patients. Int Immunopharmacol. 2020;84:106504. https://doi.org/10.1016/j.intimp.2020.106504

9Lagunas-Rangel FA. Neutrophil-to-lymphocyte ratio and lymphocyte-to-C-reactive protein ratio in patients with severe coronavirus disease 2019 (COVID-19): A meta-analysis. J Med Virol. 2020;92:1733–1734. https://doi.org/10.1002/jmv.25819

10Data on file, Eli Lilly and Company and/or one of its subsidiaries.

11Marconi VC, Ramanan AV, de Bono S, et al; COV-BARRIER Study Group. Efficacy and safety of baricitinib for the treatment of hospitalised adults with COVID-19 (COV-BARRIER): a randomised, double-blind, parallel-group, placebo-controlled phase 3 trial. Lancet Respir Med. 2021;9(12):1407-1418. https://doi.org/10.1016/S2213-2600(21)00331-3

12Kalil AC, Patterson TF, Mehta AK, et al; ACTT-2 Study Group Members. Baricitinib plus remdesivir for hospitalized adults with covid-19. N Engl J Med. 2021;384(9):795-807. https://doi.org/10.1056/NEJMoa2031994

13Beigel J. Clinical trial update: JAK inhibitors in COVID-19. Abstract presented at: Therapeutics for COVID-19 Virtual Conference; October 8, 2020.

Date of Last Review: May 12, 2022


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