psoriatic arthritis

Researchers investigate whether tofacitinib is an effective treatment for psoriatic arthritis, as an alternative to the drugs currently prescribed.

Psoriatic arthritis is a systemic chronic inflammatory disease that affects the joints, tendons, and ligaments, and occurs in approximately 6% to 42% of patients with psoriasis. Currently, treatment guidelines for psoriatic arthritis recommend the use of synthetic disease-modifying antirheumatic drugs such as methotrexate, which are actually treatments for rheumatoid arthritis used to slow down disease progression. If these treatments are ineffective in psoriatic arthritis patients, the next step in the treatment guidelines is to administer biologic disease-modifying antirheumatic drugs. However, researchers are looking into alternative potential treatments which are more specific to psoriatic arthritis.

Finding Treatments Specific to Psoriatic Arthritis

During an immune response, cell-signaling molecules called cytokines are released to aid cell communication and stimulate the movement of cells towards the inflammation site. Modulating these pathways such as inhibiting the immune response is an ideal therapeutic target for arthritis.

The drug tofacitinib is a kinase inhibitor, which can be taken as an oral therapeutic. It uses an alternative mechanism to the current treatments available for psoriatic arthritis. Kinase inhibitors like tofacitinib can influence the signalling of a number of cytokines that are part of the pathogenesis of psoriatic arthritis.

Investigating Tofacitinib as a Potential Treatment

A recent study published in The New England Journal of Medicine by researchers in the United States investigated the efficacy and safety of the use of tofacitinib as a potential treatment for patients with psoriatic arthritis who had previously had an inadequate response to synthetic disease-modifying antirheumatic drugs. Patients were monitored over a period of 12 months and randomly assigned to either tofacitinib, the active control adalimumab (a biologic disease-modifying antirheumatic drug), or a placebo. Patients receiving the placebo were switched to either a high or low dose of tofacitinib at the three-month period.


Significant Improvement Found with Tofacitinib

The results of this double-blind phase III clinical trial showed that after three months, participants in the tofacitinib group had a response rate of 50%. This is a significant improvement from the start of the study in regards to the number of tender and swollen joints. When the dose of tofacitinib was doubled, the response rate increased to 61%, compared to the placebo group which had a response rate of only 33%. The adalimumab group, on the other hand, had a response rate of 52%.

Patients were also assessed with the Health Assessment Questionnaire-Disability Index (HAQ-DI), where a higher score indicated greater disability. For the group receiving a lower dose of tofacitinib, patients HAQ-DI scores were reduced by 0.35, whereas those receiving double the dose had a reduction in disability score of 0.40. In the placebo group however, the average score was only reduced by 0.18 and the adalimumab group had an average reduction of 0.38.

Adverse events were also recorded and the rate of these events throughout the 12-month period was 66% for the low dose tofacitinib group, 71% for the group who received the higher dose of tofacitinib and 72% for the adalimumab group. Patients who received the placebo and switched to the low dose of tofacitinib has adverse event rate of 69% and the patients who were switched to the higher dose of tofacitinib had a rate of 64%. Also, during the trial four patients receiving tofacitinib were reported to have cancer, three had serious infections and four had herpes zoster.

Tofacitinib Efficacy Superior to Placebo

Overall the results showed that after three months, the efficacy of tofacitinib (at either dosage) was superior to the placebo in patients with psoriatic arthritis who previously were not responding to the more traditional treatments prescribed.

The trial showed no significant difference in the overall outcomes for patients receiving tofacitinib or adalimumab, but this trial was not designed to compare these two treatments. The researchers noted, however, that adverse events were more frequent in the groups receiving tofacitinib in comparison to the placebo. Also, there was no significant difference in efficacy for the tofacitinib groups receiving different dosages of the drug. Future studies are essential to investigate the long-term efficacy and safety of tofacitinib as a possible treatment for patients with psoriatic arthritis.

Written by Lacey Hizartzidis, PhD

Reference: van Vollenhoven RF, Fleischmann R, Cohen S, Lee EB, García Meijide JA, Wagner S, Forejtova S, Zwillich SH, Gruben D, Koncz T, Wallenstein GV, Krishnaswami S, Bradley JD, Wilkinson B; ORAL Standard Investigators. Tofacitinib or adalimumab versus placebo in rheumatoid arthritis. N Engl J Med. 2012 Aug 9;367(6):508-19. doi: 10.1056/NEJMoa1112072. Erratum in: N Engl J Med. 2013 Jul 18;369(3):293.

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