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Xeljanz

Active Substance: tofacitinib citrate
Common Name: tofacitinib citrate
Active Substance: tofacitinib citrate
Status: Refused
Authorisation Date: 0000-00-00
Therapeutic Area: Arthritis, Rheumatoid

Therapeutic Indication

Breast cancer

Docetaxel Accord in combination with doxorubicin and cyclophosphamide is indicated for the adjuvant treatment of patients with:

  • operable node-positive breast cancer;
  • operable node-negative breast cancer.

For patients with operable node-negative breast cancer, adjuvant treatment should be restricted to patients eligible to receive chemotherapy according to internationally established criteria for primary therapy of early breast cancer.

Docetaxel Accord in combination with doxorubicin is indicated for the treatment of patients with locally advanced or metastatic breast cancer who have not previously received cytotoxic therapy for this condition.

Docetaxel Accord monotherapy is indicated for the treatment of patients with locally advanced or metastatic breast cancer after failure of cytotoxic therapy. Previous chemotherapy should have included an anthracycline or an alkylating agent.

Docetaxel Accord in combination with trastuzumab is indicated for the treatment of patients with metastatic breast cancer whose tumours overexpress HER2 and who previously have not received chemotherapy for metastatic disease.

Docetaxel Accord in combination with capecitabine is indicated for the treatment of patients with locally advanced or metastatic breast cancer after failure of cytotoxic chemotherapy. Previous therapy should have included an anthracycline.

Non-small-cell lung cancer

Docetaxel Accord is indicated for the treatment of patients with locally advanced or metastatic non-small-cell lung cancer after failure of prior chemotherapy.

Docetaxel Accord in combination with cisplatin is indicated for the treatment of patients with unresectable, locally advanced or metastatic non-small-cell lung cancer, in patients who have not previously received chemotherapy for this condition.

Prostate cancer

Docetaxel Accord in combination with prednisone or prednisolone is indicated for the treatment of patients with hormone refractory metastatic prostate cancer.

Gastric adenocarcinoma

Docetaxel Accord in combination with cisplatin and 5-fluorouracil is indicated for the treatment of patients with metastatic gastric adenocarcinoma, including adenocarcinoma of the gastroesophageal junction, who have not received prior chemotherapy for metastatic disease.

Head and neck cancer

Docetaxel Accord in combination with cisplatin and 5-fluorouracil is indicated for the induction treatment of patients with locally advanced squamous cell carcinoma of the head and neck.

What is Xeljanz?

Xeljanz is a medicine that contains the active substance tofacitinib. It was to be available as tablets (5 mg).

What was Xeljanz expected to be used for?

Xeljanz was expected to be used in the treatment of moderate to severe active rheumatoid arthritis (an immune system disease causing damage and inflammation in the joints). It was to be used in patients in whom treatment with at least one other medicine known as a biological disease-modifying antirheumatic drug (biological DMARD1), had been unsuccessful either because patients were unable to tolerate treatment due to side effects, or because they did not respond adequately.


1Biological DMARDs are medicines that target specific proteins in the immune system. They are produced by a method known as ‘recombinant DNA technology’: they are made by cells that have received a gene (DNA) that makes them able to produce the medicine.

How was Xeljanz expected to work?

The active substance in Xeljanz, tofacitinib, is an immunosuppressant (a medicine that reduces the activity of the immune system) that works by blocking the action of enzymes known as Janus kinases. These enzymes play an important role in the process of inflammation and damage of the joints that occurs in rheumatoid arthritis. By blocking the enzymes, tofacitinib is expected to reduce the inflammation and other symptoms of the disease.

What did the company present to support its application?

The effects of Xeljanz were first tested in experimental models before being studied in humans.

The company initially presented the results of five main studies of safety and effectiveness involving over 3,300 patients with rheumatoid arthritis. These studies compared Xeljanz (in a dose of 5 or 10 mg twice daily) with placebo (a dummy treatment), either alone or as an addition to other background medicines (DMARDs). The main measures of effectiveness were changes in patient scores for signs and symptoms of disease, physical function of the patient, structural damage to joints and disease activity; these were measured after three or six months, depending on the study.

What were the CHMP’s main concerns that led to the refusal?

The CHMP had major concerns about the overall safety profile of Xeljanz. There were significant and unresolved concerns about the risk and type of serious infections seen with tofacitinib, which are related to the immunosuppressant action of the medicine.

These safety concerns also included a risk of other severe side effects including certain cancers, gastro-intestinal perforations (holes in the wall of the gut), liver damage and problems with increased lipid (fat) levels in the blood. It was not clear that these risks could be managed successfully in medical practice.

In April 2013, the Committee considered that, taken together, the data from the five main studies showed that treatment with Xeljanz resulted in an improvement in the signs and symptoms of rheumatoid arthritis and the physical function of patients. However, the studies were not sufficient to show a consistent reduction in disease activity and structural damage to joints, particularly at the lower 5-mg dose of Xeljanz and in the target population of patients in whom treatment with at least two other DMARDs has been unsuccessful. At re-examination in July 2013, the company proposed to remove claims of an effect on structural damage from the indication. However, the lack of robust evidence on prevention of structural damage with Xeljanz in the proposed dose and population still contributed to the Committee’s view that the benefits of treatment did not outweigh significant and unresolved concerns about safety.

Therefore, in April 2013 the CHMP was of the opinion that the benefits of Xeljanz did not outweigh its risks and recommended that it be refused marketing authorisation. The CHMP refusal was confirmed after re-examination.

What consequences does this refusal have for patients in clinical trials or compassionate-use programmes?

The company informed the CHMP that patients receiving tofacitinib in clinical trials will continue to receive it as planned. The company will consider future requests for compassionate use on an individual basis in accordance with local regulations.

If you are in a clinical trial or compassionate-use programme and need more information about your treatment, contact the doctor who is giving it to you.

Source: European Medicines Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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