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Xeljanz belongs to a new class of therapies called Janus kinase (JAK) inhibitors. It can be prescribed in combination with methotrexate for patients who have responded inadequately to or who are intolerant to disease-modifying antirheumatic drugs (DMARDs), or as monotherapy when methotrexate is inappropriate or not tolerated.
The 5mg tablets are given twice daily.
New drug class
Further information
View tofacitinib drug record Summary of Product Characteristics Manufacturer: PfizerJAK inhibitors directly target the Janus kinase signalling pathway, working inside the cell by binding to a site on the JAK enzyme. This prevents JAK from activating the STAT proteins, thus interrupting the signalling channel and halting the message that ultimately produces the inflammatory response seen in RA.
Clinical trial programme
The efficacy and safety of tofacitinib were investigated in six Phase III trials comprising the ORAL programme.
ORAL Solo was a placebo-controlled trial of tofacitinib monotherapy in 611 RA patients with an inadequate response to DMARDs. At 3 months, the investigators found a significant improvement in the tofacitinib groups compared with the placebo groups in RA signs and symptoms (ACR20 response rate 65.7% with tofacitinib 10mg vs 26.7% with placebo, p<0.001) and physical function.
ORAL Sync was a placebo-controlled trial of tofacitinib combination therapy in 792 RA patients with an inadequate response to non-biologic DMARD therapy. Results showed a significant difference for tofacitinib-treated patients versus placebo-treated patients in RA signs and symptoms at 6 months and physical function at 3 months.
ORAL Standard was a placebo- and adalimumab-controlled trial of tofacitinib plus methotrexate in 717 RA patients with an inadequate response to methotrexate. Again, there was a significant difference for tofacitinib-treated patients versus placebo-treated patients in RA signs and symptoms at 6 months and physical function at 3 months. Outcomes seen with tofacitinib were numerically similar to those seen with adalimumab.
ORAL Step was a placebo-controlled trial of tofacitinib plus methotrexate in 399 RA patients with an inadequate response to TNF antagonists. Tofacitinib treatment was associated with significant improvements in disease activity and physical function compared with placebo at 3 months.
ORAL Scan was a placebo-controlled 24-month trial of tofacitinib plus methotrexate in 797 RA patients with an inadequate response to methotrexate. Interim results demonstrated that tofacitinib reduced disease activity and radiographic progression of structural damage at 6 months compared with placebo, and improved physical function at 3 months.
ORAL Start showed that tofacitinib was superior to methotrexate as a single agent in reducing RA signs and symptoms and inhibiting radiographic progression of structural joint damage in methotrexate-naive patients (n=958).
Risk of infections
The most common serious adverse reactions to tofacitinib are serious infections, including pneumonia, cellulitis and herpes zoster. Patients should be closely monitored for infections during and after treatment, and the risks and benefits of tofacitinib should be considered before starting treatment in patients:
- with recurrent infections
- with a history of a serious or an opportunistic infection
- who have resided or travelled in areas of endemic mycoses
- who have underlying conditions that may predispose them to infection.
The most commonly reported adverse reactions to tofacitinib during the first 3 months in controlled clinical trials were headache, upper respiratory tract infections, nasopharyngitis, diarrhoea, nausea and hypertension.
Monitoring of lymphocyte and neutrophil counts, haemoglobin levels and lipids is recommended.
