Philip J. Mease, MD: There were 2 phase 3 trials, known as DISCOVER-1 and DISCOVER-2 that led to the approval of guselkumab in the treatment of psoriatic arthritis, which is relatively recent. In DISCOVER-1, which was a smaller trial, about 30% of the patients had been treated with TNF [tumor necrosis factor] agents previously and 70% were bio-naïve. In that study, the ACR20 response at 24 weeks—the primary end point—was highly statistically significant compared with placebo. Two dose arms of guselkumab were studied, giving it every 8 weeks, which is the same as the psoriasis dosing, or giving it every 4 weeks. As it turns out, the approval is for every 8 weeks, and the data with that showed an ACR20 response of 52%. The skin scores were very high, with 76% of patients achieving a PASI 75 [Psoriasis Area and Severity Index decrease of 75%], for example, and in the psoriasis trials those numbers are even higher. Guselkumab is turning out to be, like the other IL-23s, 1 of the best agents we have in treating the psoriasis component. There was also very meaningful resolution of enthesitis and dactylitis with guselkumab in this trial.
In DISCOVER-2, this was a completely bio-naïve population. Here we saw two-thirds of patients achieving an ACR20 response at week 24 and high rates of resolution of enthesitis and dactylitis, very high skin responses, and improvement in patient-reported outcomes, such as function, pain, and fatigue. Interestingly, this trial was 1 of the first that led to the FDA allowing in the claim or in the label for guselkumab to say that it can benefit fatigue. We know that that’s a very important issue for our psoriatic arthritis patients, and so this is actual recognition of them.
In that trial, the every-4-week dose was able to show statistically significant ability to inhibit structural damage progression by x-ray. The every-8-week dose just barely missed that. It looks like the drug is able to benefit, but it could be a dose issue. Safety profile was very good, with very low rates of serious infection. There was no signal for things like cancer, cardiovascular events, herpes zoster, malignancy, or inflammatory bowel disease, so a very reassuring safety profile was achieved.
In the more recent meeting, we saw a very interesting study with guselkumab in which the spondylitis aspect of PsA [psoriatic arthritis] was explored. I use the word explored because it wasn’t a definitive study with MRI scans and so forth, but it was an effort to see whether the drug would benefit the symptoms of spine disease. The reason this is an interesting question is because historically we’ve seen 1 agent, a similar P19/IL-23 inhibitor, have a trial in ankylosing spondylitis and not show benefit compared with placebo. We’ve also seen the same with ustekinumab, which is an IL-12 and IL-23 inhibitor. There was some question about whether the drug would work in the spine. In this subset analysis, patients who had clearly abnormal, sacroiliac joints on x-ray and had elevated spine pain scores—and were considered by the investigator to have axial PsA [psoriatic arthritis]—were included. We saw with both dose arms of guselkumab clear improvement of spine-related symptoms in the form of improvement of BASDAI [Bath Ankylosing Spondylitis Disease Activity Index], the spine pain question, the ASDAS [Ankylosing Spondylitis Disease Activity Score]. So it gives us some window into the idea that maybe the IL-12/IL-23 inhibitor is working in axial PsA [psoriatic arthritis], even though another agent didn’t seem to work in ankylosing spondylitis. We know that there are enough differences between axial PsA [psoriatic arthritis] and ankylosing spondylitis that maybe there is some immunobiologic reason why this would be the case. This is going to be further explored. Again, I consider this data exploratory, and we’ll see more learning about whether IL-23s worked well in axial PsA in the future.
Transcript Edited for Clarity