Treatment Guidelines for Immune-Mediated Inflammatory Diseases

Introduction to JAK Inhibitors

JAK inhibitors, including baricitinib, tofacitinib, peficitinib, upadacitinib, and filgotinib, are indicated for patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) who have failed prior conventional synthetic DMARDs and/or biological therapies, with established efficacy in various conditions, according to the European League Against Rheumatism and the American College of Rheumatology 1, 2
JAK inhibitors work by blocking intracellular signaling pathways, inhibiting Janus kinases (JAKs) which are essential for the signaling of multiple inflammatory cytokines, with different JAK inhibitors having varying selectivity profiles, such as tofacitinib (JAK1, JAK3, and JAK2), baricitinib (JAK1 and JAK2), upadacitinib (JAK1), and filgotinib (JAK1) 1

The standard dose of baricitinib is 2 mg or 4 mg once daily, with dose adjustments required for patients over 70 years, renal impairment, and severe hepatic disease, according to the European League Against Rheumatism 1
Dose adjustments are necessary for patients with renal impairment, including a reduced dose of 2 mg daily for patients with CrCl 30-60 mL/min, and baricitinib is not recommended for patients with CrCl <30 mL/min, as per the European League Against Rheumatism 1
For RA patients in sustained remission, consider dose reduction, and in RA, consider adding a JAK inhibitor to continued csDMARDs if the patient tolerates the csDMARD 1

The American College of Rheumatology recommends a complete patient history and physical examination, including assessment of previous/current infections, history of TB or TB exposure, malignancy history, cardiovascular risk factors, and history of venous thromboembolism, before initiating baricitinib treatment 1
Laboratory testing, including complete blood count, liver function tests, renal function tests, lipid profile, and hepatitis B and C screening, is recommended before and during baricitinib treatment, according to the American College of Rheumatology 1
Complete blood count and liver transaminase tests should be performed at 1 and 3 months, then every 3 months, with lipid levels checked at month 3 after starting treatment 1

JAK inhibitors are contraindicated in patients with severe active or chronic infections, current malignancies, severe organ dysfunction, pregnancy and lactation, or recurrent venous thromboembolism (unless anticoagulated) 1
Baricitinib is contraindicated in patients with severe active infections, severe hepatic disease, severe renal disease, pregnancy, and lactation, and should be used with caution in patients with a history of recurrent infections, patients over 65 years, history of malignancy, and cardiovascular risk factors, as per the European League Against Rheumatism 1

JAK inhibitors are associated with an increased risk of serious infections, herpes zoster, and venous thromboembolism, particularly in patients over 65 years and those with cardiovascular risk factors, according to the European League Against Rheumatism 1
Laboratory abnormalities, including lymphopenia, thrombocytopenia, neutropenia, anemia, and lipid elevations, have been observed in patients treated with baricitinib, according to the European League Against Rheumatism 1
Increased risk of venous thromboembolism has been reported with tofacitinib 10 mg twice daily and baricitinib, and annual skin examination is recommended for detection of skin cancer 1

The American College of Rheumatology recommends that patients with HBsAg positive status avoid baricitinib or use it with antiviral prophylaxis, and that patients with HBcAb positive/HBsAg negative status be monitored for HBV reactivation 1
Contraception is advised for both female and male patients, and baricitinib should be discontinued at least 4 weeks before planned conception, as per the European League Against Rheumatism 1
JAK inhibitors offer the advantage of oral administration compared to injectable biologics, but should not be used in combination with biologic DMARDs or potent immunosuppressants 1
For evaluation of response, be aware that CRP and ESR may be reduced independently of reduction of disease activity 1

For peripheral arthritis in PsA, TNF inhibitors, IL-17 inhibitors, and JAK inhibitors are equally recommended based on evidence including head-to-head studies, according to EULAR recommendations 3
For axial disease in PsA, TNF inhibitors, IL-17 inhibitors, and JAK inhibitors are all recommended based on evidence from axial spondyloarthritis studies 3
JAK inhibitors should be considered after failure of at least one bDMARD, or when a bDMARD is not appropriate, according to EULAR recommendations 2