Pharmakokinetics: Secukinumab is available as a SC injection or lyophilized powder for injection. Its peak plasma concentration is 13.7 mcg/mL (150 mg dose) and 27.3 mcg/mL (300 mg dose); elimination half-life is 22–31 days.
3.
Indications and Dosage: Secukinumab is indicated for moderate to severe plaque psoriasis in patients who are candidates for systemic therapy or phototherapy. Initial loading dose is 300 mg SC at weeks 0, 1, 2, 3, and 4, followed by monthly maintenance (300 mg SC or 150 mg SC monthly). For adults with active PsA and moderate to severe plaque psoriasis, the same recommendations are followed. For patients with psoriatic arthritis as well as AS, administer with or without a loading dosage by SC injection; 150 mg SC every 4 weeks with or without MTX is recommended.
4.
Adverse Effects: As for any of these biologics, infection is a common side effect (28.7%). Nasopharyngitis occurs in about 12%. TB status should be evaluated prior to therapy. Secukinumab may exacerbate Crohn’s disease.
1. Mechanism of Action: Tofacitinib is a targeted synthetic small molecule (tsDMARD) that selectively inhibits all members of the Janus kinase (JAK; see Chapter 2) family to varying degrees. At therapeutic doses, tofacitinib exerts its effect mainly by inhibiting JAK3, and to a lesser extent JAK1, hence interrupting the JAK-STAT signaling pathway. This pathway plays a major role in the pathogenesis of autoimmune diseases including RA. The JAK3/JAK1 complex is responsible for signal transduction from the common γ-chain receptor (IL2RG) for IL-2, -4, -7, -9, -15, and -21, which subsequently influences transcription of several genes that are crucial for the differentiation, proliferation, and function of NK cells and T and B lymphocytes. In addition, JAK1 (in combination with other JAKs) controls signal transduction from IL-6 and interferon receptors. RA patients receiving tofacitinib rapidly reduce C-reactive protein.
2.
Pharmacokinetics: The recommended dose of tofacitinib in the treatment of RA is 5 mg twice daily; there is a clear trend to increased response (and increased toxicity) at double this dose. In 2016, the FDA approved extended-release (XR) tofacitinib citrate 11 mg tablets for once-daily treatment. Tofacitinib has an absolute oral bioavailability of 74%, high-fat meals do not affect the AUC, and the elimination half-life is about 3 hours. Metabolism (of 70%) occurs in the liver, mainly by CYP3A4 and to a lesser extent by CYP2C19. The remaining 30% is excreted unchanged by the kidneys. Patients taking CYP enzyme inhibitors and those with moderate hepatic or renal impairment require dose reduction to 5 mg once daily. It should not be given to patients with severe hepatic disease.
3.