Jakinibs

Jakinibs are a class of small-molecule medications that inhibit the activity of the Janus kinase (JAK) family, including JAK1, JAK2, JAK3, and TYK2, within the JAK-STAT signaling pathway. By blocking the phosphorylation of JAKs, they reduce activation of STAT transcription factors and downregulate the expression of various pro-inflammatory cytokines. Inhibitor selectivity varies, with some agents acting broadly on multiple JAKs and others targeting specific JAK family members, influencing therapeutic effects and safety profiles.

Jakinibs are used to treat a range of autoimmune and inflammatory conditions. Indications include rheumatoid arthritis, psoriatic arthritis, ulcerative colitis, Crohn’s disease, and atopic dermatitis, as well as graft-versus-host disease. They also have roles in certain myeloproliferative neoplasms such as myelofibrosis and polycythemia vera, and are employed in veterinary medicine for allergic skin disease in dogs. Examples often cited among this class include tofacitinib, ruxolitinib, baricitinib, upadacitinib, filgotinib, fedratinib, deucravacitinib, and oclacitinib.

Administration and monitoring vary by agent, but most jakinibs are taken orally, with some topical formulations available for skin disease. Because they suppress immune function, initiating therapy typically involves evaluation for latent infections and ongoing monitoring for infections, thrombosis, anemia, thrombocytopenia, lipid changes, liver enzymes, and other adverse effects. Drug interactions, especially with strong CYP3A4 inhibitors or inducers, can alter drug exposure and safety.

Safety considerations include an elevated risk of serious infections, herpes zoster, thromboembolic events, cytopenias, dyslipidemia, and potential malignancy risk. Regulatory agencies emphasize careful patient selection, monitoring, and risk mitigation when using jakinibs.