As you can recall, psoriatic arthritis is a type of autoimmune disease that affects people with psoriasis.  In certain cases, it can look like rheumatoid arthritis, but it is very different condition.  Rheumatologists use medications like sulfasalazine, methotrexate, Otezla, as well as multiple TNF inhibitors such as Enbrel and Humira to treat psoriatic arthritis. Other medications include Cosentyx, an interleukin 17 inhibitor, as well as Orencia.

Tofacitinib or adalimumab versus placebo for psoriatic arthritis

Recently, researchers studied whether tofacitinib, also known as Xeljanz, could also give some benefit for people with psoriatic arthritis.  A recent study published in the New England Journal of medicine reported the results of the oral psoriatic arthritis trial (OPAL) Broaden, the phase 3 trial which evaluated the efficacy and safety of tofacitinib and adalimumab, also known as Humira, compared to placebo.  Here are the results.

Methods

Design

• The study lasted 12 months.
• Everyone had to be on at least one conventional or non-biologic DMARD such as methotrexate, sulfasalazine, or leflunomide.
• The trial was a randomized, placebo-controlled, double-blind phase 3 trial.
• People were randomly assigned to receive the following regimens:
  • Tofacitinib 5 mg taken orally twice daily
  • Tofacitinib 10 mg taken orally twice daily
  • Adalimumab 40 mg subcutaneously once every two weeks
  • Placebo with a switch to 5 mg dose of two presented at month three, or placebo with a switch to 10 mg dose of two presented at month three
• Everyone had to be on a stable background dose of either, methotrexate, sulfasalazine, or leflunomide.

The trial was sponsored by Pfizer.

Primary and secondary endpoints

• The two primary endpoints assessed at month three were:
  • The percentage of people who achieved an American College of Rheumatology 20 (ACR20) response
  • And the change from baseline Health Assessment Questionnaire – Disability Index (HAQ-DI).

The ACR20 is a composite measure defined as both improvement of 20% in the number of tender and number of swollen joints, and a 20% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure [most often Health Assessment Questionnaire (HAQ)], visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP).

ACR50 and ACR70 are the same instruments with improvement levels defined as 50% and 70% respectively versus 20% for ACR20

• Secondary endpoints included the amount of people who achieved an ACR50 or more and an ACR70 or more. The researchers looked at the improvement in people’s psoriasis as well as enthesitis (i.e., inflammation of tendons, ligaments, and bursae).
• The researchers also looked at x-rays of the hands and feet at baseline and at month 12, to see whether they had worsened on treatment.
• They assessed safety by means of spontaneous reporting of adverse events – physical examinations, and clinical laboratory test.

Results

Efficacy

373 people completed the trial.

• At 3 months, ACR20 response was:
  • 50 % in the 5-mg tofacitinib group
  • 61% in the 10-mg tofacitinib group
  • 52% in the adalimumab group
  • 33% in the placebo group
• At 3 months, the ACR 50 response was:
  • 28% in the 5-mg tofacitinib group
  • 40% in the 10-mg tofacitinib group
  • 33% in the adalimumab group
  • 10% in the placebo group
• At 3 months, the ACR70 response was:
  • 17% in the 5-mg tofacitinib group
  • 14% in the 10-mg tofacitinib group
  • 19% in the adalimumab group
  • 5% in the placebo group
• At month 12, 90% among people who received tofacitinib or adalimumab did not show any worsening of their disease on x-ray.
• Both tofacitinib and adalimumab performed better than placebo
• They both performed similarly but in all fairness, the study wasn’t powered to accurately compare the two.

Safety

• At 3 months, the percentage of people with adverse events:
  • 39% in the 5-mg tofacitinib group
  • 45% in the 10-mg tofacitinib group
  • 46% in the adalimumab group
  • 35% in the placebo group
• At 3 months serious adverse events occurred in:
  • 3% of the 5-mg tofacitinib group
  • 1% of the 10-mg tofacitinib group
  • 1% of the adalimumab group
  • 1% of the placebo group
• At 12 months, the percentage of people with serious adverse events
  • 7% of people in the 5-mg tofacitnib group
  • 4% of the people in the 10-mg tofacitinib group
  • 8% in the adalimumab group
• The most common adverse events were sinusitis, upper respiratory tract infections, and headaches.
• One cardiac arrest happened in the placebo group at month 4, i.e., 1 month after switching to tofacitinib.
• There were 4 cases of shingles that occurred in the groups receiving tofacitinib.
• Three cases of cancer occurred: day 1, day 11, and day 231 of the trial.

Conclusion

Tofacitinib is effective in treating psoriatic arthritis at 3 months and after one year of treatment.  The rates of adverse effects are more than placebo but comparable to current standard of care.

References

Mease P, et al. Tofacitinib or adalimumab versus placebo for psoriatic arthritis.N Engl J Med. 2017 Oct 19;377(16):1537-1550.

Medical Disclaimer

This information is offered to educate the general public. The information posted on this website does not replace professional medical advice, but for general information purposes only. There is no Doctor – Patient relationship established. We strongly advised you to speak with your medical professional if you have questions concerning your symptoms, diagnosis and treatment.