From the Guidelines
Janus kinase (JAK) inhibitors for rheumatoid arthritis typically include medications like tofacitinib (Xeljanz), baricitinib (Olumiant), upadacitinib (Rinvoq), and filgotinib (Jyseleca), with the standard regimen for tofacitinib being 5 mg twice daily or 11 mg extended-release once daily, baricitinib at 2-4 mg once daily, upadacitinib at 15 mg once daily, and filgotinib at 100-200 mg once daily, as recommended by recent guidelines 1.
Key Considerations
- These medications are often prescribed when conventional disease-modifying antirheumatic drugs (DMARDs) like methotrexate have failed to provide adequate relief, and may be used alone or in combination with methotrexate.
- Before starting treatment, patients should undergo screening for tuberculosis, hepatitis B and C, and have baseline blood work including complete blood count, liver function tests, and lipid panel, as suggested by various studies 1.
- Regular monitoring is essential, with blood tests recommended every 1-3 months initially, then every 3-6 months once stable, to minimize potential side effects and ensure optimal treatment outcomes.
Mechanism of Action and Side Effects
- JAK inhibitors work by blocking intracellular signaling pathways that contribute to inflammation, effectively interrupting the inflammatory cascade that causes joint damage in rheumatoid arthritis, as explained in a study on the treatment of immune-mediated inflammatory diseases with JAK inhibitors 1.
- Patients should be aware of potential side effects including increased risk of infections, herpes zoster reactivation, changes in blood counts, elevated liver enzymes, and increased cholesterol levels, and vaccination status should be updated before initiating therapy, particularly for pneumococcal and herpes zoster vaccines, as recommended by guidelines for the management of rheumatoid arthritis 1.
Treatment Approach
- Treatment decisions should follow a shared decision-making process, and should be reevaluated within a minimum of 3 months based on efficacy and tolerability of the DMARD(s) chosen, with the goal of reaching a predefined target of low disease activity or remission, as suggested by the American College of Rheumatology guideline for the treatment of rheumatoid arthritis 1.
- A treat-to-target approach involving frequent monitoring of disease activity using validated instruments and modification of treatment to minimize disease activity is recommended, with the aim of achieving low disease activity or remission in the majority of patients, as supported by evidence from various studies 1.
From the FDA Drug Label
XELJANZ/XELJANZ XR/XELJANZ Oral Solution is a Janus kinase (JAK) inhibitor indicated for: • Rheumatoid Arthritis: XELJANZ/XELJANZ XR is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to one or more TNF blockers Recommended Dosage Rheumatoid Arthritis • XELJANZ 5 mg twice daily or XELJANZ XR 11 mg once daily.
The Janus protocol treatment regimen for rheumatoid arthritis using Janus kinase inhibitors like Tofacitinib is 5 mg twice daily or 11 mg once daily with XELJANZ XR 2.
- The dosage may be adjusted based on renal impairment or hepatic impairment.
- It is recommended to use XELJANZ or XELJANZ XR in patients who have had an inadequate response or intolerance to one or more TNF blockers.
- XELJANZ/XELJANZ XR should not be used in combination with biologic DMARDs or potent immunosuppressants.
From the Research
Janus Protocol Overview
- The Janus protocol, also known as Janus kinase inhibitors, is a treatment regimen used for conditions like rheumatoid arthritis.
- Janus kinase inhibitors, such as baricitinib and tofacitinib, have been approved for the treatment of at least moderately active rheumatoid arthritis after the failure of conventional disease modifying anti-rheumatic drugs 3.
- These inhibitors can be taken orally and reversibly inhibit Janus kinases (JAK) and therefore the signaling of a large number of cytokines via the JAK/STAT pathway.
Treatment Regimen
- Baricitinib and tofacitinib have been shown to be at least as efficacious in rheumatoid arthritis as adalimumab, and tofacitinib was also efficacious in psoriatic arthritis 3.
- The treatment regimen typically involves a daily dose of 2-4 mg of baricitinib or 5-10 mg of tofacitinib 4, 5.
- The choice of dose and treatment duration depends on the individual patient's response and medical history.
Efficacy and Safety
- Studies have shown that Janus kinase inhibitors are effective in reducing disease activity and improving symptoms in patients with rheumatoid arthritis 6, 4.
- However, there are concerns regarding major adverse cardiovascular events (MACE) and venous thromboembolism (VTE) associated with JAK inhibitors 7.
- The safety profile of baricitinib and tofacitinib is comparable to that of biologic disease-modifying anti-rheumatic drugs, with a slightly higher risk of herpes zoster and VTE 3, 4.
Comparison of JAK Inhibitors
- A study comparing the efficacy of tofacitinib, baricitinib, upadacitinib, and filgotinib found that filgotinib and upadacitinib are equivalent therapeutic alternatives, while baricitinib and upadacitinib are also equivalent due to a lack of clear differences 6.
- However, there is some inconsistency in the results of tofacitinib compared to upadacitinib, and more data are needed to fully understand the comparative efficacy and safety of these JAK inhibitors.