Olumiant ® (baricitinib) tabletter

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Olumiant® ▼ (baricitinib): Opportunistiska infektioner

Fall av opportunistiska infektioner var sällsynta i kliniska prövningar med baricitinib i reumatoid artrit

Special warnings and precautions for use related to Infections

BARI is associated with an increased rate of infections such as upper respiratory tract infections compared to placebo. In treatment naïve patients, combination with methotrexate resulted in increased frequency of infections compared to BARI monotherapy. The risks and benefits of treatment with BARI should be carefully considered prior to initiating therapy in patients with active, chronic or recurrent infections. If an infection develops, the patient should be monitored carefully and BARI therapy should be temporarily interrupted if the patient is not responding to standard therapy. BARI treatment should not be resumed until the infection resolves.1

Patients should be screened for tuberculosis (TB) before starting baricitinib therapy. BARI should not be given to patients with active TB. Anti-TB therapy should be considered prior to initiation of BARI in patients with previously untreated latent TB.1

Identification of Potential Opportunistic Infections

Identification of OIs in the clinical trial program employed both a screening and a manual review step.2

  • The screening step used 2 approaches to select relevant cases: 1 using a prespecified list of MedDRA preferred terms and the other using a prespecified list of infecting organisms and infection sites as reported by the investigator on an infection-specific case report form.

  • All events with at least 1 infecting organism were also manually reviewed to identify relevant cases. All relevant cases were subject to detailed review of all available clinical data, including information in the Lilly Safety System that may not be in the clinical trial database.

Safety Dataset Descriptions

4-Study Extended Dataset

The extended dataset included patients with RA randomized to BARI 4 mg (N=479) or BARI 2 mg (N=479) from 2 phase 2 and 2 phase 3 studies and 1 long term extension study. The evaluation time periods included randomization through last available observation incorporating extension data through 13 February 2018 unless otherwise specified. Data were censored at rescue or dose change.3

All BARI RA Dataset

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. Data includes a long-term extension study with

  • data through 13 February 2018, and

  • 10,127 PYE.3

Opportunistic Infections in the Baricitinib Clinical Development Program

Incidence rates of OIs for the All BARI Dataset, 4-Study Extended Dataset, and 7-Study Placebo-Controlled Dataset are presented in Table 1.

TB and HZ in the BARI clinical trial program are not discussed extensively in this response.

Incidence of Opportunistic Infections in the 4-Study Extended Dataset

In the extended dataset, incidence rates per 100 PYE for OIs excluding multidermatomal HZ and TB were

  • 0.3 for BARI 2 mg, and

  • 0.3 for BARI 4 mg.4

There were no evident dose-related effects.2

Incidence rates of multidermatomal HZ and TB are presented in Table 1

Incidence and Types of Opportunistic Infections in All BARI RA Dataset

In the All BARI RA dataset, the incidence rate per 100 PYE for OIs excluding multidermatomal HZ and TB was 0.3.4

Opportunistic infections reported for patients in the ALL BARI RA dataset included

  • 26 cases of multidermatomal HZ

  • 15 cases of TB

  • 12 cases of invasive Candida infection, including 8 cases of esophageal candidiasis

  • 4 cases of Pneumocystis jirovecii pneumonia

  • 4 cases of cytomegalovirus, and

  • 1 case each of aspergillus, cryptococcal, histoplasmosis, paracoccidioides, Epstein Barr virus, disseminated herpes simplex, and strongyloidiasis infections.2,3,5

Summary of Opportunistic Infections

Table 1. Summary of Opportunistic Infections Through 13 February 20182-5


 

 

 






7-Study Placebo-controlled Dataset to Week 24a

4-Study Extended Datasetb

All BARI RA c

Placebo
N=1215 (451 PYE)
n (IR)

BARI 2 mg
N=479 (186 PYE)
n (IR)

BARI 4 mg
N=1142 (472 PYE)
n (IR)

BARI 2 mg
N=479 (676 PYE)
n (IR)

BARI 4 mg
N=479 (699 PYE)
n (IR)

Phases 1-3
N=3770 (10,127 PYE)
n (IR)

OI including multidermatomal herpes zoster

2 (0.5)

0

4 (0.9)

2 (0.3)

3 (0.4)

52 (0.5)

OI excluding multidermatomal herpes zosterde

1 (0.2)

0

3 (0.7)

2 (0.3)

2 (0.3)

27 (0.3)

Multidermatomal herpes zosterf

1 (0.2)

0

1 (0.2)

0

1 (0.1)

26 (0.3)g

Tuberculosis

0

0

1 (0.2)

0

7 (0.5)

15 (0.2)

Abbreviations: BARI = baricitinib; HZ = herpes zoster; IR = incidence rate per 100 PYE; OI = opportunistic infection; PYE = patient-years exposure; RA = rheumatoid arthritis.

a The 7-study placebo-controlled dataset includes patients with RA who were randomized to placebo (n=1215), BARI 2 mg (n=479), and BARI 4 mg (n=1142) from 7 phase 2 and 3 trials with data through 24 weeks.

b The extended dataset included patients with RA randomized to BARI 4 mg or BARI 2 mg from 4 phase 2 and 3 studies and 1 long term extension study. The evaluation time periods included randomization through last available observation incorporating extension data through 13 February 2018 unless otherwise specified. Data was censored at rescue or dose change.

c 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. Data includes a long-term extension study with data through 13 February 2018.

d Includes the following OIs: histoplasmosis, pneumonia cryptococcal, Pneumocystis jirovecii pneumonia, invasive candidiasis, cytomegalovirus infection, Paracoccidioides infection, Aspergillus species infection, Epstein-Barr virus infection, disseminated herpes simplex, strongyloidiasis.

e Excludes tuberculosis.

f Multidermatomal herpes zoster, as defined by HZ infection distributed beyond primary and adjacent dermatomes.

g Includes an additional case reported as "disseminated zoster" that was not included in the total opportunistic infection number.

References

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

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

3. 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

4. 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.

5. Chen YH, Chen YM, Smolen J, et al. Incidence rate and characterization of herpes zoster events in patients with moderate to severe rheumatoid arthritis: an update from baricitinib clinical trials. Ann Rheum Dis. 2019;78(2):755. http://dx.doi.org/10.1136/annrheumdis-2019-eular.1130.

Glossary

BARI = baricitinib

HZ = herpes zoster

Lilly = Eli Lilly and Company

MedDRA = Medical Dictionary for Regulatory Activities

OI = opportunistic infection

PYE = patient-years of exposure

RA = rheumatoid arthritis

TB = tuberculosis

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.

Datum fӧr senaste ӧversyn 2019 M03 08


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