Tofacitinib
On the basis of the phase 3 OPAL Beyond (N Engl J Med. 2017 Oct 19;377[16]:1525-36) and OPAL Broaden (N Engl J Med. 2017 Oct 19;377[16]:1537-50) clinical trials, the dose approved by the Food and Drug Administration for psoriatic arthritis was 5 mg b.i.d.. There was a higher ACR20 response rate with 10 mg than 5 mg b.i.d. in OPAL Broaden, but not in OPAL Beyond. And since there was a suggestion of a higher adverse event rate with the 10-mg b.i.d. dosing without unequivocal evidence of superior efficacy, the Food and Drug Administration – which always puts safety first – went with 5 mg b.i.d., Dr. Ruderman explained.
Ixekizumab
In the phase 3, double-blind SPIRIT-P1 trial, featuring 417 biologic-naive psoriatic arthritis patients, the ACR20 response rate at week 24 was 62.1% with the interleukin-17A antagonist at 80 mg given subcutaneously every 2 weeks and 57.9% when dosed every 4 weeks, compared with 57.4% with adalimumab(Humira) at 40 mg every 2 weeks and 30.2% with placebo (Ann Rheum Dis. 2017 Jan;76[1]:79-87). The FDA-approved regimen was a 160-mg loading dose of ixekizumab, followed by 80 mg every 4 weeks.
Dr. Kavanaugh noted that an international team of investigators has identified beta-defensin 2 as an easily measurable biomarker of interleukin-17A–driven skin pathology after evaluating 170 proteins expressed in blood, psoriasis lesions, and nonlesional skin. It was a small study, with eight psoriasis patients and eight healthy controls studied before and after receiving secukinumab(Cosentyx), a monoclonal antibody directed against interleukin-17A (J Allergy Clin Immunol. 2017 Mar;139[3]:923-932.e8). But it’s a study with big potential implications.
“This natural antibiotic compound we make that’s in the skin might be a marker of responsiveness to anti–interleukin-17 therapy. It could help in deciding which patients get which drugs. This needs further study, especially now that we’re using anti–interleukin-17 drugs more now,” the rheumatologist said.
The year 2017 also brought important new studies of several drugs already available for psoriatic arthritis.