Tofacitinib citrate, brand name Xeljanz, is a U.S. Food and Drug Administration-approved drug to treat  (RA). The drug, distributed by Pfizer, is a Janus kinase (JAK) inhibitor.

RA is a chronic inflammatory disease, initiated by an unknown external factor that triggers an autoimmune reaction leading to increased thickness of the synovial membranes and to joint inflammation.

The immune system relies on chemical signals spread throughout cells, allowing them to initiate and maintain an inflammatory state capable of “knocking out” threats or invaders. Circulating chemical molecules are recognized by receptors that exist in cells and activate a group of proteins inside the cell called JAKs. This activation is crucial to the chain of events that lead to the formation of new chemical molecules, which spread the “danger” signal to other cells, thus maintaining inflammation for as long as is necessary to clear out the threat.

How tofacitinib (Xeljanz) works

In RA patients, the amount of chemical molecules circulating in cells is higher than normal because cells are constantly producing them, further spreading a message that inflammation should be maintained.

Tofacitinib works by inhibiting JAK proteins inside the cell. The chemical signal is still spread from cell to cell but, because JAKs are not activated, that signal does not generate the new molecules needed to further inflammation to other cells.

Tofacitinib has the ability to help RA patients by decreasing inflammation, thereby reducing pain.

Studies of tofacitinib (Xeljanz) in RA

A Phase 3, randomized, double-blind, and placebo-controlled clinical trial (NCT00814307) of tofacitinib evaluated changes in joint inflammation in adult patients with mild to severe RA during a six-month period. Blood test were also analyzed to measures inflammation.

After two weeks of treatment, results showed that 30% of patients (71 out of 240) experienced a 20% reduction in tender and swollen joint counts. Three months later, 59% (143 out of 243) experienced the same results.

A RA disability scale ( 0-1, mild; 1-2, moderate to severe; 2 or more, severe disability) was used during the study. On average, after three months of treatment, patients experienced an improvement of 1.05 units in their score, and 60% (143 out of 240) of  patients  experienced an improvement greater than 0.22 units.

Six months after treatments started, disability scores worsened by 0.2 units in treated RA patients compared to the trial’s start, while those given methotrexate (an immune system suppressor and common RA treatment ) worsened by 0.8 units.

Other details and side effects 

Xeljanz is approved for use only in patients for whom methotrexate did not work well. An oral medication, two tablet forms are available: an immediate-release pill that requires patients take two daily doses of Xeljanz (5 mg each), and an extended release table that requires one daily dose of 11 mg. The FDA-recommended dose is 5 mg twice daily.

The FDA warns that use of JAK inhibitors may carry an increased risk of serious infections, tuberculosis, cancers and lymphoma, as well as high cholesterol, respiratory tract infections, headache, and diarrhea in some patients.