Damian McNamara

November 14, 2017

SAN DIEGO — For patients with active psoriatic arthritis, the human interleukin (IL)-17A antagonist secukinumab (Cosentyx, Novartis Pharmaceuticals), administered by subcutaneous injection, significantly improved disease activity at 16 weeks, according to interim results from the ongoing FUTURE5 study (NCT02404350).

And at 24 weeks, treatment was associated with an inhibition of the radiographic progression of psoriatic arthritis.

"The musculoskeletal efficacy is similar to the TNFs, and, in the skin, it's superior," said investigator Philip Mease, MD, from the Swedish Medical Center and the University of Washington in Seattle.

And, "the safety profile is good," he told Medscape Medical News.

Dr Mease presented 16- and 24-week data on 996 adults with active psoriatic arthritis during a late-breaking poster session here at the American College of Rheumatology (ACR) 2017 Annual Meeting.

The first 16 weeks of the study involved four treatment groups: 222 patients received secukinumab 300 mg with a loading dose, 220 received secukinumab 150 mg with a loading dose, 222 received secukinumab 150 mg with no loading dose, and 332 received placebo. At week 16, nonresponders in the placebo group were switched to one of the treatment groups.

In the study cohort, mean age was 49 years, mean duration of psoriatic arthritis was just over 7 years, 50% of the participants were women, 70% had never used a TNF inhibitor, and 50% were using concomitant methotrexate.

For all end points, secukinumab was more effective in patients who had never received a TNF inhibitor than in those who had.

Significantly more patients in the secukinumab groups than in the placebo group achieved a 20% improvement in disease activity (ACR20), the primary end point. Not surprisingly, onset of response was earlier in the regimens that involved a loading dose.

Table 1. 16-Week Outcome

  With Loading Dose Without Loading Dose  
Outcome Secukinumab 300 mg Secukinumab 150 mg Secukinumab 150 mg Placebo P Value
ACR20 63% 56% 60% 27% <.0001

 

At week 24, the inhibition of radiographic progression of psoriatic arthritis — a secondary end point — was significantly better with secukinumab 300 mg plus loading dose than with placebo (P < .01), with 150 mg plus loading dose (P < .05), and with 150 mg without loading dose (P < .01).

During the study period, there were no deaths in any of the treatment groups.

Table 2. Adverse Event Rates at Week 16

  With Loading Dose Without Loading Dose
Event Secukinumab 300 mg, % Secukinumab 150 mg, % Secukinumab 150 mg, % Placebo, %
Adverse event 52.0 53.0 53.0 59.0
Serious adverse event 2.3 3.2 1.4 3.0

 

This is the first study to demonstrate that subcutaneous secukinumab 300 mg and 150 mg dosing regimens inhibit radiographic progression, the researchers point out.

At week 24, inhibitions in radiographic progression, defined as a change of 0.5 or less change from baseline in modified total van der Heijde Sharp score, were significantly greater in every secukinumab group than in the placebo group.

Patients were more likely to experience no radiographic progression if they received secukinumab 300 mg with loading dose, 150 mg with loading dose, or 150 mg without loading dose than if they received placebo (88% vs 79% vs 83% vs 73%).

Other secondary outcomes included reduction in Psoriasis Area and Severity Index (PASI) score of 75% and 90%, ACR50, quality of life as indicated by the Health Assessment Questionnaire–Disability Index (HAQ-DI) score, and 28-joint disease activity score using C-reactive protein (DAS28-CRP).

Table 3. Secondary End Points at Week 16

  With Loading Dose Without Loading Dose
End Point Secukinumab 300 mg Secukinumab 150 mg Secukinumab 150 mg Placebo
PASI 75 responders, % 70 60 58 12
PASI 90 responders, % 54 37 32 9
ACR50 responders, % 40 36 32 8
Enthesitis resolution, % 56 55 42 35
Dactylitis resolution, % 66 58 56 32
Change from baseline
HAQ-DI score –0.55 –0.44 –0.45 –0.21
DAS28-CRP score –1.49 –1.29 –1.29 –0.63

 

"A lot of rheumatologists don't know" the mechanism of IL-17 inhibition, Dr Mease explained. They will likely be "intrigued" by this study, which is the largest randomized controlled trial of a biologic for psoriatic arthritis to date.

In this study of the functional scores and structural changes in almost 1000 patients with psoriatic arthritis over 4 months, "it does look like secukinumab led to improvement in a very high percentage of patients," said Bharat Kumar, MD, from the University of Iowa Hospitals and Clinics in Iowa City.

"Just as important, it looks like it is relatively safe," he told Medscape Medical News. After seeing these results, "I would be much more likely to prescribe secukinumab for psoriatic arthritis patients who didn't respond well to the more established psoriatic arthritis medications."

This study was funded by Novartis. Dr Mease reports financial ties with Novartis, AbbVie, Amgen, BMS, Celgene, Crescendo Bioscience, Corrona, Demira, Genentech, Janssen, Lilly, Pfizer, Sun, UCB, and Zynerba. Dr Kumar has disclosed no relevant financial relationships.

American College of Rheumatology (ACR) 2017 Annual Meeting: Abstract 17L. Presented November 7, 2017.

Follow Medscape on Twitter @Medscape and Damian McNamara @MedReporter

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