Can tofacitinib (Janus kinase inhibitor) be used in the treatment of inflammatory arthritis?

Tofacitinib in Inflammatory Arthritis

Tofacitinib can be used in inflammatory arthritis, but it should be considered after biological DMARD treatment has failed due to safety concerns and limited long-term data. 1, 2

Classification and Positioning in Treatment Algorithm

• Tofacitinib is a Janus kinase (JAK) inhibitor classified as a targeted synthetic DMARD (tsDMARD), not a conventional synthetic DMARD (csDMARD) or biological DMARD (bDMARD) 1
• Tofacitinib is approved for various inflammatory arthritis conditions including rheumatoid arthritis (RA) and psoriatic arthritis (PsA) 1
• According to EULAR recommendations, tofacitinib should be positioned after biological treatment has failed in the treatment algorithm 1, 2

Efficacy in Inflammatory Arthritis

• Clinical studies have shown that tofacitinib alone (as first- or second-line treatment) or combined with a csDMARD is effective in reducing signs and symptoms of inflammatory arthritis 3
• Tofacitinib improves health-related quality of life during long-term therapy (up to 96 months) 3
• In RA patients with inadequate response to prior DMARDs, tofacitinib 5 mg twice daily demonstrated significantly higher ACR20, ACR50, and ACR70 response rates compared to placebo 4
• Tofacitinib has shown comparable efficacy to adalimumab (a TNF inhibitor) when combined with methotrexate, although the studies were not powered for formal comparisons 4

Safety Considerations

• Tofacitinib has been generally well tolerated during treatment periods up to 114 months, with most adverse events being mild or moderate in severity 3
• The most common adverse events are infections and infestations 3, 1
• Herpes zoster infections appear to be more common with tofacitinib than with TNF inhibitors 1, 2
• Several cases of tuberculosis and non-TB opportunistic infections have been reported 1, 2
• Hematologic abnormalities including lymphocytopenia and anemia have been observed 1, 2
• Recent data showed tofacitinib at 10 mg twice daily was associated with an increased risk of venous thromboembolism (VTE) and pulmonary embolism (PE) in patients with RA who have cardiovascular risk factors 1
• A warning has also been issued for the 5 mg twice daily dose regarding VTE risk 1

Specific Recommendations by Condition

Rheumatoid Arthritis

• The recommended dose for RA is 5 mg twice daily 1, 5
• Tofacitinib should be considered after failure of biological DMARDs 1, 2
• It can be used as monotherapy in case of intolerance or contraindications to methotrexate and other csDMARDs 1

Psoriatic Arthritis

• Tofacitinib is approved for the treatment of active PsA 1
• It has shown efficacy in treating peripheral arthritis, dactylitis, and enthesitis in PsA patients 1

Axial Spondyloarthritis

• JAK inhibitors including tofacitinib are recommended when bDMARDs (TNF inhibitors or IL-17 inhibitors) are contraindicated or unavailable 1
• The PANLAR guidelines recommend initially considering TNF inhibitors and IL-17 inhibitors over JAK inhibitors for axial spondyloarthritis 1

Special Populations and Dose Adjustments

• Dose reduction is recommended in patients with a creatinine clearance of <30 mL/min 1, 5
• Tofacitinib is contraindicated in patients with severe hepatic impairment (Child Pugh C) 1, 5
• In patients ≥65 years old with a history of smoking or risk factors for cardiovascular disease or malignancy, JAK inhibitors should be used only if no suitable alternatives exist 1

Monitoring Recommendations

• Regular monitoring for infections, particularly herpes zoster, is essential 2
• Monitor complete blood counts due to potential hematologic abnormalities 2
• Screen for tuberculosis before initiating therapy 2
• Be aware that C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) may be reduced independently of reduction of disease activity, potentially masking infections 1

Treatment Algorithm for Inflammatory Arthritis

1. Start with conventional synthetic DMARDs (particularly methotrexate) as first-line therapy 1, 2
2. If treatment targets are not reached with csDMARDs, consider biological DMARDs (TNF inhibitors, IL-17 inhibitors, etc.) 1
3. After failure of biological DMARDs, consider tofacitinib as a treatment option 1, 2
4. In patients where bDMARDs are contraindicated or unavailable, tofacitinib may be considered earlier in the treatment algorithm 1