Olumiant®▼ (baricitinib): Risk and Comorbid COVID-19 in Rheumatoid Arthritis Patients

Baricitinib and COVID-19

Baricitinib is not approved for the treatment of COVID-19, COVID-19 pneumonia, or COVID-19. Please see local labeling for approved indications.

COVID-19 Risk or Prevention in Patients with Rheumatoid Arthritis Treated with Baricitinib

Although BARI is being studied for the treatment of COVID-19, it is unknown if patients treated with baricitinib for rheumatoid arthritis are at a greater risk of both contracting COVID-19 and having COVID-19 related complications.

Clinical Registry Data for Patients With Rheumatological Disorders and COVID-19

Clinical registries have been formed to collect data from patients with rheumatic diseases and COVID-19. These registries have assessed baseline medications for rheumatoid arthritis as well as COVID-19 clinical outcomes.^1-6

To date, publications from these registries have reported an insufficient volume of patients treated with JAK inhibitors, including BARI, to draw conclusions regarding risk of contracting COVID-19, risk for COVID-19 related complications or any potential protective effect of JAK inhibitors.^2,4-7

Risks and Outcomes of COVID-19 in the Autoimmune Population

Analyses on the risks and outcomes of COVID-19 in patients with autoimmune disease, including rheumatoid arthritis, have been published. Please see references for relevant citations.^8-11

Efficacy and Safety of Baricitinib in Patients With Rheumatoid Arthritis and COVID-19

An analysis of the efficacy and safety of baricitinib in patients with RA and COVID-19 has not been conducted. 

Baricitinib Infection-Related Warnings and Precautions

COVID-19 is an active respiratory disease, which is typically mild but may lead to acute respiratory distress syndrome which can be lethal. Please note the important BARI infection-related warnings and precautions listed below for consideration.

Baricitinib is associated with an increased rate of infections such as upper respiratory tract infections compared to placebo. In rheumatoid arthritis clinical studies, in treatment naïve patients, combination with methotrexate resulted in increased frequency of infections compared to baricitinib monotherapy.¹²

The risks and benefits of treatment with baricitinib should be carefully considered prior to initiating therapy in patients with active, chronic or recurrent infections.¹²

If an infection develops, the patient should be monitored carefully and baricitinib therapy should be temporarily interrupted if the patient is not responding to standard therapy. Baricitinib treatment should not be resumed until the infection resolves.¹²

Incidence of Infections in Baricitinib Clinical trials

Upper Respiratory Tract Infections

Upper respiratory tract infections were very commonly (≥10%) reported adverse events in RA BARI clinical trials.¹³

Table 1. Infections and Upper Respiratory Tract Infections From Rheumatoid Arthritis Clinical Trials in the Placebo-Controlled Period^13-15

Abbreviations: BARI = baricitinib; EAIR = exposure adjusted incidence rate; IR = incidence rate; PYE = patient-years of exposure; TE = treatment emergent.

^a The 7-study pooled dataset included patients with RA randomized to BARI 4 mg (N=1142, PYE=471.8) or placebo (N=1215, PYE=450.8) from 3 phase 2 studies and 4 phase 3 studies. Patients in the placebo group could have been taking background MTX or other conventional DMARDs. Data from BARI 2 mg (N=479, PYE=185.8) is derived from 4 of these studies in which both BARI 2 mg and BARI 4 mg were options during randomization. 

^b Includes acute sinusitis, epiglottitis, laryngitis, nasopharyngitis, oropharyngeal pain, pharyngitis, pharyngotonsillitis, rhinitis, sinusitis, sinobronchitis, tonsillitis, tracheitis, and upper respiratory tract infection.

Serious Infections in Rheumatoid Arthritis Clinical Trials

The All BARI RA analysis set included 3770 patients with RA who received BARI at a variety of doses from 1 phase 1, 3 phase 2, and 5 phase 3 studies (RA-BEGIN, RA-BEAM, RA-BUILD, RA-BEACON, RA-BALANCE). Data includes a long-term extension study (RA-BEYOND) with

• data through 13 February 2018

• 10,127 PYE, and

• up to 6.9 years of exposure.^14,15

Of the 3770 patients who received BARI in the RA clinical trials through 13 February 2018, there were 283 TE serious infections with an IR per 100 PYE, censored at time of event, of 2.8. The most frequent serious infections reported were

• pneumonia (n=52, EAIR 0.5)

• HZ (n=35, EAIR 0.4)

• urinary tract infection (n=21, EAIR 0.2)

• cellulitis (n=15, EAIR 0.2)

• sepsis (n=18 including 14 cases of sepsis and 4 cases of urosepsis), and

• gastroenteritis (n=13, EAIR 0.13).^13-15

Clinical Factors Associated with Serious Infection

A large group of clinical factors with the potential to affect the risk of serious infection was evaluated using Cox models and data from the All BARI RA dataset through 01 January 2016. The 5 independent risk factors identified for serious infection were

• prior biologic use

• advanced age

• Asian region of study enrollment, excluding Japan

• non-normal body mass index, and

• concomitant corticosteroid use.³

Additionally, increasing grades of lymphopenia were associated with an increase in frequency of any TE infection and serious infection in BARI-treated patients.¹³

Clinical Use

The treating physician may use the information provided, the patient’s prior medical history and concomitant medications, and other individual factors, in formulating an assessment and approach. The treating physician should consider potential risks and benefits of treatment options, and monitor appropriately.

Infectious Disease Resources

For the most current information regarding COVID-19, please refer to the WHO, ECDC and EULAR websites:

• World Health Organization at https://www.who.int/emergencies/diseases/novel-coronavirus-2019

• European Centre for Disease Prevention and Control at https://www.ecdc.europa.eu/en/covid-19-pandemic and

• European League Against Rheumatism at https://www.eular.org/rheumatism_and_covid_19.cfm

References

1. Gianfrancesco M, Hyrich KL, Al-Adely S, et al. Characteristics associated with hospitalisation for COVID-19 in people with rheumatic disease: data from the COVID-19 Global Rheumatology Alliance physician-reported registry. Ann Rheum Dis. Published online May 29, 2020. http://dx.doi.org/10.1136/annrheumdis-2020-217871

2. Gianfrancesco MA, Hyrich KL, Gossec L, et al. Rheumatic disease and COVID-19: initial data from the COVID-19 Global Rheumatology Alliance provider registries. Lancet Rheumatol. Published online April 16, 2020. https://doi.org/10.1016/S2665-9913(20)30095-3

3. Winthrop KL, Genovese MC, Harigai M, et al. Serious infection and associated risk factors in patients with moderate to severe rheumatoid arthritis treated with baricitinib [abstract OP0248]. Ann Rheum Dis. 2017;76(suppl 2):158. http://ard.bmj.com/content/76/Suppl_2/158.2

4. Scirè CA, Carrara G, Zanetti A, et al. Italian Registry of the Italian Society for Rheumatology (CONTROL-19). COVID-19 in rheumatic diseases in Italy: first results from the Italian registry of the Italian Society for Rheumatology (CONTROL-19). Clin Exp Rheumatol. 2020 Jul-Aug;38(4):748-753. https://www.clinexprheumatol.org/article.asp?a=15906

5. Michaud K, Wipfler K, Shaw Y, et al. Experiences of Patients With Rheumatic Diseases in the United States During Early Days of the COVID-19 Pandemic. ACR Open Rheumatol. 2020 Jun;2(6):335-343. https://doi.org/10.1002/acr2.11148

6. Hasseli R, Mueller-Ladner U, Schmeiser T, et al. National registry for patients with inflammatory rheumatic diseases (IRD) infected with SARS-CoV-2 in Germany (ReCoVery): a valuable mean to gain rapid and reliable knowledge of the clinical course of SARS-CoV-2 infections in patients with IRD. RMD Open. 2020;6:e001332. http://dx.doi.org/10.1136/rmdopen-2020-001332

7. Winthrop KL, Brunton AE, Beekmann S, et al. SARS CoV-2 infection among patients using immunomodulatory therapies. Ann Rheum Dis. Published online August 5, 2020. http://dx.doi.org/10.1136/annrheumdis-2020-218580

8. Freites Nuñez DD, Leon L, Mucientes A, et al. Risk factors for hospital admissions related to COVID-19 in patients with autoimmune inflammatory rheumatic diseases. Annals of the Rheumatic Diseases 2020;79(11):1393-9. https://www.doi.org/10.1136/annrheumdis-2020-217984

9. Akiyama S, Hamdeh S, Micic D, et al. Prevalence and clinical outcomes of COVID-19 in patients with autoimmune diseases: a systemic review and meta-analysis. Ann Rheum Dis. 2020. http://dx.doi.org/10.1136/annrheumdis-2020-218946

10. Favalli EG, Monti S, Ingegnoli F, et al. Incidence of COVID-19 in patients with rheumatic diseases treated with targeted immunosuppressive drugs: what can we learn from observational data? Arthritis Rheum. 2020;72(10):1600-1606. http://dx.doi.org/10.1002/art.41388

11. Haberman RH, Castillo R, Chen A, et al. COVID-19 in patients with inflammatory arthritis: a prospective study on the effects of comorbidities and DMARDs on clinical outcomes. Arthritis Rheumatol. 2020. http://dx.doi.org/10.1002/art.41456

12. Olumiant [summary of product characteristics]. Eli Lilly Nederland B.V., The Netherlands.

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

14. Genovese MC, Smolen JS, Takeuchi T, et al. Safety profile of baricitinib for the treatment of rheumatoid arthritis up to 7 years: an updated integrated safety analysis. Ann Rheum Dis. 2019;78(2):308-309. http://dx.doi.org/10.1136/annrheumdis-2019-eular.691

15. Genovese MC, Smolen JS, Takeuchi T, et al. Safety profile of baricitinib for the treatment of rheumatoid arthritis up to 7 years: an updated integrated safety analysis. Presented as an oral presentation at: European League Against Rheumatism (EULAR) Annual Meeting; June 12-15, 2019; Madrid, Spain.

Glossary

BARI = baricitinib

COVID-19 = coronavirus disease 2019

EAIR = exposure-adjusted incidence rate

ECDC = European Center for Disease Prevention and Control

EULAR = European League Against Rheumatism

JAK = Janus kinase

PYE = patient-years of exposure

RA = rheumatoid arthritis

TE = treatment-emergent

US = United States

WHO = World Health Organization

▼ This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions.