Matthew Gall 

Baricitinib (Olumiant) is a Janus kinase (JAK) inhibitor indicated for the treatment of rheumatoid arthritis (RA) and COVID-19 in hospitalized adults requiring supplemental oxygen, noninvasive or invasive ventilation, or extracorporeal membrane oxygenation (ECMO).

A study enrolled 684 patients with RA who had inadequate response or intolerance to conventional synthetic disease-modifying antirheumatic drugs (DMARDs) but were naïve to biologic DMARDs. The researchers randomly assigned study participants 1:1:1 to either receive a placebo, a 2 mg dose, or 4 mg dose of baricitinib with the primary endpoint measure being achievement of ACR20.

This is a standardized score created by the American College of Rheumatology to measure the response and efficacy of RA treatment. Reaching ACR20 means that the patient has achieved a 20% improvement in the severity of their RA symptoms.

At 12 weeks of patients receiving baricitinib 2 mg and 4 mg, 66% and 62% achieved ACR20, with only 39% of the patients reaching the same endpoint with placebo. At 24 weeks, the rates for the placebo, 2 mg, and 4 mg dosage were 42%, 61%, and 65%, respectively.

The European Union approved both the 2 mg and 4 mg dosages in early 2017. When baricitinib reached American markets in 2018, the FDA approved only the 2 mg, dosage citing the primary reason as the increased risk of thrombosis associated with the 4 mg dosing.

In a subsequent randomized study, researchers evaluated the effects of treatment with baricitinib plus remdesivir on time to recovery and clinical status in 1033 patients, with 515 administered combination therapy and 518 administered remdesivir monotherapy. Patients receiving combination therapy had faster time to recovery, with a median time of 7 days compared to the control group’s time of 8 days.

This difference in recovery was even greater in patients receiving high flow oxygen. Median recovery time in this group was 10 days while patients in the control had a time of 18 days.

Patients receiving baricitinib also displayed lower 28-day mortality compared to the remdesivir monotherapy control group, at 5.1% and 7.8%, respectively. Incidence of all adverse events (AEs)—ordinary, serious, and fatal—was also lower in the combination therapy cohort. Sixteen percent of patients receiving baricitinib experienced serious AEs compared to 21% in the control population.

In early November 2020, the FDA granted emergency use authorization for the use of baricitinib in treating COVID-19 infection. It recently 

Baricitinib is a small molecule JAK inhibitor to modulate the immune response via reduction of Signal Transducers and Activators of Transcription (STATs) activation.

 Take 4 mg orally once daily for 14 days or until hospital discharge, whichever comes first. If patients cannot swallow tablets, alternate administration can be used.

 Interrupt baricitinib until ALC ≥500 cells/µL.

Patients with ANC <1000 cells/microliter: Interrupt treatment until ANC ≥1000 cells/µL.

Patients with hemoglobin <8 g/deciliter: Interrupt treatment until hemoglobin ≥8 g/dL.

Patients with severe renal impairment: Not recommended.

Patients with ALC <200 cells/microliter: Interrupt baricitinib until ALC ≥200 cells/µL.

Patients with ANC <500 cells/microliter: Interrupt treatment until ANC ≥500 cells/µL.

Patients with moderate renal impairment: 2 mg once daily.

Patients with severe renal impairment: 1 mg once daily.

Consider discontinuation of OAT3 inhibitor.

Significant AEs include serious infections, mortality, malignancy, major cardiovascular AEs, thrombosis, gastrointestinal perforations, laboratory abnormalities, and hypersensitivity.

Prescribers should avoid baricitinib in patients with active, serious infection; patients at risk of thrombosis; and patients with an active tuberculosis (TB) infection.

Provider should discuss baricitinib’s benefits and risks with patients with a history of TB or who have risk factors for TB infection.

Reactivation of herpes zoster has been reported. If a patient develops an active episode, prescribers should interrupt therapy until the episode resolves.

Non-melanoma skin cancers have been reported with baricitinib use, and patients at risk for skin cancer should schedule periodic skin examinations.

If a patient exhibits clinical features of thrombosis, prescribers should discontinue baricitinib therapy.

Patients on baricitinib should have routine testing of liver enzymes, lipid levels, ANC, ALC, and hemoglobin to monitor for any abnormalities.

Patients taking baricitinib should avoid live vaccines.

There are insufficient data on the effects of baricitinib in pregnant patients to inform a conclusion on the risk of miscarriage or major birth defects. Patients should discuss with their provider the risks and benefits of starting baricitinib while pregnant.

There are currently no data on the presence of baricitinib in human breast milk. Based on the presence in animal breastmilk, the manufacturer advises that patients treated with baricitinib not breastfeed.

Matthew Gall is a 2024 PharmD candidate at the University of Connecticut.

1. Olumiant Prescribing Information. Lilly USA Inc.; May 2022.

2. Felson DT, LaValley MP. The ACR20 and defining a threshold for response in rheumatic diseases: too much of a good thing. 

3. Dougados M, van der Heijde D, Chen YC, et al. Baricitinib in patients with inadequate response or intolerance to conventional synthetic DMARDs: results from the RA-BUILD study [published correction appears in Ann Rheum Dis. 2017;76(9):1634]. 

. 2017;76(1):88-95. doi:10.1136/annrheumdis-2016-210094

4. Mogul A, Corsi K, McAuliffe L. Baricitinib: The Second FDA-Approved JAK Inhibitor for the Treatment of Rheumatoid Arthritis. 

. 2019;53(9):947-953. doi:10.1177/1060028019839650 Accessed May 12, 2022

5. Kalil AC, Patterson TF, Mehta AK, et al. Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19. 

. 2021;384(9):795-807. doi:10.1056/NEJMoa2031994

Articles

Baricitinib (Olumiant) is indicated for the treatment of rheumatoid arthritis and COVID-19 in hospitalized adults.

Clinical Overview: Baricitinib (Olumiant) for Rheumatoid Arthritis, COVID-19

Lifitegrast ophthalmic solution (Xiidra) is a lymphocyte function-associated antigen-1 (LFA-1) antagonist indicated for the treatment of symptoms associated with dry eye disease (DED) in adults.

In a clinical trial, researchers randomized 811 participants with DED to receive either lifitegrast or a placebo in a 1:1 ratio to measure the reduction in eye dryness score (EDS). The EDS ranges from 0 to 100, with 0 being no discomfort and 100 being maximum discomfort.

All participants had an EDS of 40 or higher. The researchers monitored changes in EDS at days 14, 42, and 84 with lifitegrast 5%, and the study was powered to measure reductions in EDS by 6.5, 8.0, and 10.0 units, respectively.

Lifitegrast improved EDS significantly compared with placebo, with participants reporting improvement as soon as day 14. Patients treated with lifitegrast also noted greater improvements in itching, foreign body sensation, and eye discomfort than those in the placebo group.

Lifitegrast binds to the integrin LFA-1 protein and blocks the interaction with its cognate ligand intracellular adhesion molecule-1 (ICAM-1). The exact mechanism of action in DED is unknown, but is suspected to be inhibition of inflammatory cytokine release from reduced T-cell adhesion to ICAM-1.

Lifitegrast 5% ophthalmic single use container: Instill 1 drop into each eye twice daily.

Pharmacists should counsel patients who use contacts to remove them prior to administration and leave them out for at least 15 minutes.

Pharmacists should counsel patients on proper technique for instilling eye drops. This should include the key points of washing their hands before and after administration and not touching the tip of the container.

Pharmacists should counsel patients that each container is single-use and should be discarded after instilling a drop in each eye.

Pharmacists should counsel patients on the possibility of dysgeusia as an adverse event (AE) to limit patient concern should it occur.

Patients should store lifitegrast 5% containers in their original foil packaging at room temperature.

The most common AEs reported were dysgeusia, instillation-site irritation, and decreased visual acuity.

Cases of patients experiencing hypersensitivity to lifitegrast were seen in post market reports.

Data regarding the use of lifitegrast 5% ophthalmic solution in pregnancy are lacking. Animal models using IV lifitegrast at 400-fold to 460-fold the human plasma exposure level found no evidence of a teratogenic effect. Patients should discuss any risk with their provider.

There are no data on the presence of lifitegrast in breastmilk, but the systemic exposure from ocular administration is low. The benefits of breastfeeding should be considered along with the mother’s clinical need for this medication and the potential AEs on the child.

Matthew Gall is a 2024 PharmD candidate at the University of Connecticut

1. Xiidra Prescribing Information. July 2016. Accessed May 8, 2022

https://www.novartis.us/sites/www.novartis.us/files/xiidra.pdf

2. Holland EJ, Luchs J, Karpecki PM, et al. Lifitegrast for the treatment of dry eye disease: results of a phase iii, randomized, double-masked, placebo-controlled trial (OPUS-3). 

. 2017;124(1):53-60. doi:10.1016/j.ophtha.2016.09.025 Accessed May 8, 2022

In clinical trials, Xiidra was found to improve eye dryness scores significantly compared with placebo.

Clinical Overview: Lifitegrast Ophthalmic Solution (Xiidra) for Dry Eye Disease

Daridorexant (Quviviq) is a dual orexin receptor (OX1R and OX2R) antagonist taken to improve sleep onset and maintenance. The 

 in January 2022 to treat insomnia and it will be available following its scheduling by the DEA. 

In 2 clinical trials that evaluated 1854 participants diagnosed with insomnia, researchers randomized patients to receive either daridorexant or a placebo to measure changes in latency to persistent sleep (LPS) and wake after sleep onset (WASO). These measures are markers of sleep onset and maintenance, respectively, therefore a reduction in these times is indicative of clinical improvement.

In the first study, researchers found that participants administered 25 mg of daridorexant had an improvement to their WASO and LPS reductions of 12 and 8 minutes more, respectively, compared to placebo at 3 months. This reduction was also seen in participants receiving the 50 mg dosing, who showed reductions of 18 and 12 minutes, respectively, compared to placebo in the same period.

The second study trialed 25 mg and 10 mg dosing. The researchers found that with the 25 mg dosing, there was a similar reduction in WASO and LPS times at 10 and 9 minutes, respectively, at 3 months. They also found no statistically significant reduction in WASO or LPS times in participants who received 10 mg doses compared to placebo over the same period.

Daridorexant is a dual antagonist on the OX1R and OX2R receptors, which suppresses the wake drive.

Daridorexant 25 mg and 50 mg: Take 1 tablet by mouth within 30 minutes of going to bed.

Daridorexant use should be avoided with strong CYP3A4 inhibitors.

Daridorexant use should be limited to 25 mg when used with moderate CYP3A4 inhibitors.

Daridorexant use should be avoided with use of strong or moderate CYP3A4 inducers.

Daridorexant use should be limited to 25 mg in patients with moderate hepatic impairment and is not recommended for use in patients with severe hepatic impairment.

Daridorexant is contraindicated in patients with narcolepsy.

The most commonly reported AEs with daridorexant are dizziness, headache, and somnolence. In the 50 mg dosage, nausea was also reported.

Daridorexant acts as a central nervous system (CNS) depressant and may lead to daytime impairment. Pharmacists should advise patients about the potential of somnolence and that taking daridorexant without a full night of sleep (7 hours) may increase this risk.

Sleep paralysis and cataplexy-like symptoms in the minutes between sleep-wake transitions have been reported with daridorexant use. Pharmacists should explain the nature of these events to the patient.

Sleep walking, sleep-driving, and other complex sleep behaviors have been reported with use of hypnotics. Patients should discontinue daridorexant if they experience complex sleep behaviors.

Concomitant use of alcohol may lead to increased CNS depression and psychomotor impairment. Pharmacists should counsel patients on the increased risk and advise them to avoid alcohol consumption when taking this medication.

Because of potential increases in somnolence and drowsiness, patients (especially the elderly) are at an increased risk for falls.

Avoid use if pregnant as there are limited data available assessing whether daridorexant causes fetal harm. Daridorexant and its metabolites are likely present in human breastmilk. Infants potentially exposed to daridorexant through breast milk should be monitored for excessive sedation.

is a 2024 PharmD candidate at the University of Connecticut

Idorsia receives US FDA approval of QUVIVIQ (daridorexant) 25 and 50 mg for the treatment of adults with insomnia. Accessed March 7, 2022.

QUVIVIQ Prescribing Information. Idorsia Pharmaceuticals US Inc. Jan 2022. Accessed March 7, 2022.

The FDA approved daridorexant in January 2022 to treat insomnia after it showed improvements in changes in latency to persistent sleep and wake after sleep onset.