Rinvoq From AbbVie, Inc

The FDA has approved Rinvoq (upadacitinib) to treat moderate to severe rheumatoid arthritis (RA) in adults who have had an inadequate response or intolerance to methotrexate (MTX).

The approval carries the limitation that its use in combination with other Janus kinase (JAK) inhibitors, biologic disease-modifying anti rheumatic drugs (DMARDs), or potent immunosuppressants, such as azathioprine and cyclosporine, is not recommended.¹ Rheumatoid arthritis affects 1.3 million Americans, causing fatigue, pain, and stiffness. Without proper treatment, RA can lead to debilitating and permanent bone and cartilage damage.²

PHARMACOLOGY AND PHARMACOKINETICS

Rinvoq is a JAK inhibitor. It modulates the signaling pathway at the point of JAKs to prevent the phosphorylation and activation of signal transducers and activators of transcription. Rinvoq is metabolized primarily by cytochrome P450 3A4, with a potential minor contribution from cytochrome P450 2D6. After oral administration, it displays a median time to maximum effect of 2 to 4 hours and a mean terminal elimination half-life of 8 to 14 hours.¹

DOSAGE AND ADMINISTRATION

The dosage for Rinvoq is 15 mg orally once daily. It is formulated as an extended-release tablet that must be swallowed whole and may be taken with or without food. Rinvoq may be used alone or in combination with MTX or other nonbiologic DMARDs. It should not be taken if the absolute lymphocyte count is less than 500 cells/mm3, the absolute neutrophil count is less than 1000 cells/mm3, or the hemoglobin level is less than 8 g/dL.¹

CLINICAL TRIALS

Rinvoq was evaluated for efficacy and safety in 5 phase 3 double-blind, multicenter, randomized studies in adult patients with moderately to severely active RA. Its role as monotherapy was evaluated both in patients who were MTX-naïve and in patients with an inadequate response to MTX. Rinvoq was studied in combination with MTX in patients who had previously responded inadequately to MTX. It was also evaluated as combination therapy with conventional DMARDs in patients with an inadequate response to either biologic or conventional DMARDs. In the 5 studies, Rinvoq met all primary end points and ranked secondary end points. The studies also found that patients taking Rinvoq, either alone or in combination with conventional DMARDs, achieved higher clinical-remission response rates than those taking MTX monotherapy or a placebo. Additionally, 2 of the studies demonstrated that treatment with Rinvoq was shown to inhibit radiographic progression.^1,2

CONTRAINDICATIONS, WARNINGS, AND PRECAUTIONS

Rinvoq carries a boxed warning regarding the risk of serious infections, malignancy, and thrombosis. Patients taking Rinvoq are at increased risk for developing serious infections that may lead to hospitalization or death. If a serious infection develops, Rinvoq should be stopped until the infection is controlled. Reported infections include bacterial, invasive fungal, tuberculosis, viral, and other opportunistic infections. Patients should be tested for latent tuberculosis before initiating treatment with Rinvoq and treated prior to taking Rinvoq if the test is positive. All patients should be monitored for active tuberculosis during treatment, even if the initial test is negative. Lymphoma and other malignancies have occurred in patients treated with Rinvoq. Thrombosis, including arterial thrombosis, deep venous thrombosis, and pulmonary embolism, has occurred in patients treated with JAK inhibitors used to treat inflammatory conditions.

There are no contraindications to treatment with Rinvoq.

Rinvoq should not be used in patients with active, serious infections, including localized infections. The benefits and risks of Rinvoq should be considered before starting treatment in patients with an increased risk of thrombosis or known malignancy. Patients with symptoms of thrombosis should be evaluated promptly and treated appropriately. Rinvoq should be used cautiously in patients with an increased risk of gastrointestinal perforation. Laboratory monitoring is recommended because of potential changes in hemoglobin, liver enzymes, lipids, lymphocytes, and neutrophils. Rinvoq should not be used in patients with severe hepatic impairment or in women who are breastfeeding or pregnant. The medication should be used cautiously in patients taking strong cytochrome P450 3A4 inhibitors and should not be coadministered with live vaccines or strong cytochrome P450 3A4 inducers.

The most common adverse reactions (≥1%) are cough, nausea, pyrexia, and upper respiratory-tract infections.¹

REFERENCE

• Rinvoq [prescribing information]. North Chicago, IL: AbbVie Inc; 2019. www.accessdata.fda.gov/drugsatfda_docs/label/2019/211675s000lbl.pdf. Updated August 2019. Accessed February 11, 2020.
• AbbVie receives FDA approval of Rinvoq (upadacitinib), an oral JAK inhibitor for the treatment of moderate to severe rheumatoid arthritis [news release]. North Chicago, IL: AbbVie Inc; August 16, 2019. https://news.abbvie.com/news/press-releases/abbvie-receives-fda-approval-rinvoq-upadacitinib-an-oral-jak-inhibitor-for-treatment-moderate-to-severe-rheumatoid-arthritis.htm. Accessed February 11, 2020.