Olumiant (Baricitinib) Once-Daily Oral Drug Approved for the Treatment of Patients with Moderately to Severely Active Rheumatoid Arthritis

March 2019, Vol 12, Tenth Annual Payers' Guide - Select Drug Profiles, Payers' Guide
Loretta Fala
Medical Writer
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Rheumatoid arthritis is a chronic inflammatory autoimmune disease that affects approximately 1.5 million people in the United States and is nearly 3 times more common in women than in men.1 Rheumatoid arthritis affects the lining or synovium of the joints, causing painful swelling that can lead to bone erosion and deformity.1,2 Other organs affected by this disease include the skin, eyes, lungs, heart, kidneys, and nerve tissue.2 Furthermore, patients with rheumatoid arthritis are at increased risk for cardiovascular diseases.3

Rheumatoid arthritis is associated with bodily pain, impaired physical function, and a low energy level, thus exerting a profound impact on the patient’s quality of life.4

The treatment of rheumatoid arthritis is aimed at reducing inflammation, alleviating symptoms, preventing joint and organ damage, and improving the patient’s functionality and well-being.5 The American College of Rheumatology (ACR) practice guidelines recommend a treat-to-target approach (achieving low disease activity or remission) for patients with early or established rheumatoid arthritis, regardless of disease activity level; however, patients with high-risk comorbidities require special consideration.6

Pharmacologic therapies for rheumatoid arthritis include nonsteroidal anti-inflammatory drugs; corticosteroids; conventional disease-modifying antirheumatic drugs (DMARDs); biologic response modifiers, a more recent class of DMARDs, including the tumor necrosis factor (TNF) inhibitor biologic drugs and the non-TNF biologic drugs; and the Janus kinase (JAK) inhibitors.6,7

FDA Approves Olumiant, an Oral JAK Inhibitor, for Rheumatoid Arthritis

On May 31, 2018, the US Food and Drug Administration (FDA) approved baricitinib (Olumiant; Eli Lilly/Incyte), an oral JAK inhibitor, for the treatment of adults with moderately to severely active rheumatoid arthritis who have had an inadequate response to 1 or more TNF antagonist therapies.8,9 Baricitinib is not recommended for use in combination with other JAK inhibitors; biologic DMARDs; or potent immunosuppressant drugs, such as azathioprine and cyclosporine.9 As part of the FDA approval, a randomized, long-term safety study will be conducted in patients with rheumatoid arthritis who received baricitinib.8

“In my clinical practice, I continue to see patients who experience debilitating symptoms and who are waiting for a medicine that may be right for them,” said Elizabeth L. Perkins, MD, Rheumatology Care Center, Birmingham, AL. “Olumiant is an important option for rheumatologists to help address these patients’ unmet needs,” added Dr Perkins.8

Mechanism of Action

Baricitinib inhibits JAKs, which are intracellular enzymes that transmit signals from cytokine or growth factor receptor interactions implicated in hematopoiesis and immune cell function.9 Baricitinib modulates the signaling pathway at the point of JAKs, thereby blocking the phosphorylation and the activation of signal transducers and activators of transcription (STATs); these STATs regulate intracellular activity, including gene expression.9

Dosing and Administration

The recommended dosage of baricitinib is 2 mg once daily administered orally as an (unscored) tablet. Baricitinib can be taken with or without food. Baricitinib can be used as monotherapy or in combination with methotrexate or other DMARDs.9

Pivotal Clinical Trials: RA-BUILD and RA-BEACON

The efficacy and safety of baricitinib 2 mg once daily were evaluated in 2 randomized, double-blind, 24-week phase 3 studies—RA-BUILD and RA-BEACON.9-11 In both studies, patients had active rheumatoid arthritis and at least 6 tender and 6 swollen joints at baseline.9 Patients received baricitinib 2 mg and 4 mg once daily or placebo, added to existing background conventional DMARD therapy; from week 16, patients whose disease did not respond to treatment could be rescued with ­baricitinib 4 mg once daily. The primary end point was the percentage of patients who achieved an improvement of ≥20% from baseline across several measures (ACR20) at week 12.9-11

RA-BUILD included 684 patients who had an inadequate response or intolerance to ≥1 conventional synthetic DMARDs. More patients who received baricitinib 2 mg once daily than those who received placebo achieved ACR20, ACR50, and ACR70 responses, and a Disease Activity Score for 28 joint counts based on the level of high-sensitivity C-reactive protein (DAS28-CRP) ≤2.6 at week 12 and week 24 (Table).9-11

Figure 1

RA-BEACON was a 24-week study that included 527 patients who had an inadequate response or intolerance to ≥1 TNF inhibitor therapies with or without other ­biologic DMARDs. More patients who received baricitinib than those who received placebo achieved ACR20, ACR50, and ACR70 responses and a DAS28-CRP ≤2.6 at week 12 and week 24 (Table). Furthermore, in this study, a greater improvement in ACR20 response was observed as early as week 1 with baricitinib 2 mg compared with placebo.9,11

Adverse Reactions

The most common (occurring in ≥1% of patients) adverse reactions associated with baricitinib 2 mg and bari­citinib 4 mg were upper respiratory tract infection (16.3% and 14.7%, respectively), nausea (2.7% and 2.8%, respectively), herpes simplex (0.8% and 1.8%, respectively), and herpes zoster (1.0% and 1.4%, ­respectively).9

At 16 weeks, adverse events led to treatment discontinuation in 17 patients who received baricitinib 2 mg versus 35 patients who received placebo.9 At 52 weeks, adverse events led to treatment discontinuation in 31 patients who received baricitinib 2 mg.9

At 16 weeks, serious infections were reported in 5 patients who received baricitinib 2 mg versus 13 patients who received placebo; no cases of venous thrombosis were reported with baricitinib 2 mg daily or with placebo, and arterial thrombosis was reported in 2 patients who received baricitinib 2 mg daily versus 1 patient who received placebo. At 52 weeks, baricitinib 2 mg was associated with serious infections in 14 patients, 2 cases of venous thrombosis, and 3 cases of arterial thromboses; no tuberculosis events were reported.9

Baricitinib has no contraindications.9

Drug Interactions

The coadministration of baricitinib with strong organic anion transporter 3 (OAT3) inhibitors increases the exposure of baricitinib; therefore, baricitinib should not be used concomitantly with OAT3 inhibitors.9

Baricitinib has not been evaluated in combination with other JAK inhibitors or with biologic DMARDs and is not recommended for use with these drugs.9

Use in Specific Populations

Baricitinib therapy is not recommended in patients with severe hepatic impairment or in patients with moderate or severe renal impairment.

In clinical trials, 537 of 3100 patients who received baricitinib were aged ≥65 years; no overall differences in the efficacy or safety of baricitinib were observed between older and younger patients.

Data on the use of baricitinib in pregnant women are insufficient to establish any potential risk for birth defects or miscarriage.9

Warnings and Precautions

The prescribing information for baricitinib contains a boxed warning about the increased risk for serious infections, malignancy, and thrombosis. Some cases of serious infection have led to hospitalization and death. The majority of patients who had infections were taking concomitant immunosuppressant drugs (ie, methotrexate or corticosteroids). These infections include active tuberculosis; invasive fungal infections, including candidiasis and pneumocystosis; and bacterial, viral, and other infections because of opportunistic pathogens.

Lymphoma and other malignancies have been reported in patients who received baricitinib; nonmelanoma skin cancers have also been reported. Increased incidences of thrombosis, some fatal, have been reported, including deep venous thrombosis, pulmonary embolism, and arterial thrombosis.9

Baricitinib should not be used in patients with active and serious infections, including localized infections. Bar­icitinib should be used with caution in patients who are at increased risk for thrombosis or gastrointestinal perforations. Baricitinib should not be used with live vaccines.9

Starting baricitinib therapy should be avoided or interrupted if a patient has anemia (hemoglobin <8 g/dL), lymphopenia (absolute lymphocyte count <500 cells/mm3), or neutropenia (absolute neutrophil count <1000 cells/mm3).9

Conclusion

The FDA approval of baricitinib, an oral JAK inhibitor, provides another treatment option for patients with moderately to severely active rheumatoid arthritis who have had an inadequate response to ≥1 TNF inhibitor therapies. In clinical trials, baricitinib 2 mg once daily demonstrated significant clinical improvement, with up to 66% of patients who had an ACR20 response at week 12 and 61% who had an ACR20 response at week 24. Furthermore, higher ACR20 response rates were observed as early as week 1 with baricitinib 2 mg compared with placebo.

References

  1. Arthritis Foundation. What is rheumatoid arthritis? www.arthritis.org/about­arthritis/types/rheumatoid-arthritis/what-is-rheumatoid-arthritis.php. Accessed October 1, 2018.
  2. Mayo Clinic. Rheumatoid arthritis: symptoms & causes. August 9, 2017. www.mayoclinic.org/diseases-conditions/rheumatoid-arthritis/symptoms-causes/syc-20353648. Accessed October 1, 2018.
  3. Arthritis Foundation. How RA inflammation affects your heart. www.arthritis.org/living-with-arthritis/comorbidities/heart-disease/ra-and-your-heart.php. Accessed October 1, 2018.
  4. Matcham F, Scott IC, Rayner L, et al. The impact of rheumatoid arthritis on quality-of-life assessed using the SF-36: a systematic review and meta-analysis. Semin Arthritis Rheum. 2014;44:123-130.
  5. Arthritis Foundation. Rheumatoid arthritis. www.arthritis.org/about-arthritis/types/rheumatoid-arthritis/. Accessed October 2, 2018.
  6. Singh JA, Saag KG, Bridges SL Jr, et al. 2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Rheumatol. 2016;68:1-26.
  7. Mayo Clinic. Rheumatoid arthritis: diagnosis & treatment. August 9, 2017. www.mayoclinic.org/diseases-conditions/rheumatoid-arthritis/diagnosis-treatment/drc-20353653. Accessed October 2, 2018.
  8. Eli Lilly and Company. FDA approves Olumiant (baricitinib) 2-mg tablets for the treatment of adults with moderately-to-severely active rheumatoid arthritis. June 1, 2018. https://investor.lilly.com/news-releases/news-release-details/fda-­approves-olumiantr-baricitinib-2-mg-tablets-treatment-adults. Accessed October 2, 2018.
  9. Olumiant (baricitinib) tablets, for oral use [prescribing information]. Indianapolis, IN: Eli Lilly and Company; May 31, 2018.
  10. 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. Ann Rheum Dis. 2017;76:88-95. Erratum in: Ann Rheum Dis. 2017;76:1634.
  11. Genovese MC, Kremer J, Zamani O, et al. Baricitinib in patients with refractory rheumatoid arthritis. N Engl J Med. 2016;374:1243-1252.
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