Friday, 14 Jun 2019

You are here

Doubling Down on IL-17 In Psoriatic Arthritis

The monoclonal antibody bimekizumab, which neutralizes both interleukin (IL)-17A and 17F, was effective for both musculoskeletal and skin outcomes in psoriatic arthritis (PsA) in a phase IIb study.

At week 12, according to Christopher T. Ritchlin, MD, of the University of Rochester in New York, a 50% improvement on the criteria of the American College of Rheumatology (ACR50) was seen in up to 46% of patients. By week 48, up to 63% of patients had ACR50 responses, he reported in a late-breaker session at the annual meeting of the American College of Rheumatology here.

In addition, a 90% improvement on the Psoriasis Area and Severity Index (PASI90) was seen in up to 54% of patients at week 12 and in up to 85% of patients at week 48.

"These results are astonishing," said Roy Fleischmann, MD, of the University of Texas Southwestern Medical Center in Dallas, who was not involved in the study. "The ACR responses are better than anything I've seen including the IL-17s and TNFs, so would you consider it for RA [rheumatoid arthritis] when other IL-17s have failed?" he asked.

"My understanding of the role of IL-17 in RA is that IL-23/17 is integral in converting anti-CCP antibodies to a more pathologic subset, and whether or not combining the inhibition of A and F would be beneficial in RA early in disease to prevent that switch isn't known. It would be an interesting study to perform," Ritchlin said.

Agents such as secukinumab (Cosentyx) and ixekizumab (Taltz) that target IL-17A have demonstrated efficacy for inflammatory diseases. But the rationale for neutralizing IL-17F in addition to IL-17A lies in the fact that the two cytokines share a 50% structural homology and have similar pro-inflammatory functions. The two also independently cooperate with other cytokines to mediate inflammation, Ritchlin explained.

To explore the possibility that greater suppression of inflammation in PsA could be achieved by inhibiting both IL-17A and F, he and his international colleagues conducted a dose-ranging study known as BE ACTIVE, which randomized 206 patients with active disease to placebo or one of four doses of subcutaneous bimekizumab every 4 weeks (16 mg, 160 mg, 160 mg with a 320-mg loading dose, or 320 mg). The double-blind phase of the trial consisted of the first 12 weeks, after which patients receiving placebo or 16 mg were re-randomized to one of the higher doses through week 48. The study was sponsored by UCB.

Patients' mean age was 50, and mean disease duration was 7 years. They had a mean of 22 tender joints and 12 swollen joints. Almost 20% had previously failed a tumor necrosis factor (TNF) inhibitor.

At week 12, ACR50 responses were seen in 7%, 27%, 42% (P<0.01 vs placebo) 46% (P<0.001 versus placebo) , and 24% of the placebo, 16-mg, 160-mg, 160-mg plus loading dose, and 320-mg groups, respectively , while PASI75 responses were observed in 7%, 45%, 64%, 77%, and 73% (P<0.01 for all versus placebo).

At week 24, 45% of patients who had been re-randomized from placebo to 160 mg had ACR50 responses, as did 50% of those re-randomized to 320 mg.

By week 48, ACR20, 50, and 70 response rates were 70%, 55%, and 43% for the 160-mg dose, 73%, 57%, and 46% for the 160-mg plus loading dose group, and 76%, 63%, and 39% for the 320-mg dose.

Moreover, PASI90 rates at week 48 were 70% for both 160-mg groups and 85% for the 320-mg dose.

Serious adverse events were reported by 4.4% of patients through week 48, and the most common treatment-emergent adverse event was nasopharyngitis. Oral candidiasis was observed in 4.9%, but there were no cases of inflammatory bowel disease, major cardiac events, or deaths.

The study was sponsored by UCB.

Ritchlin reported financial relationships with UCB, Amgen, AbbVie, Pfizer, Novartis, and Eli Lilly.

The author has no conflicts of interest to disclose related to this subject

Add new comment

More Like This

Recommendations for Exercise in Ankylosing Spondylitis

Australian researchers have assessed the problem of exercise in ankylosing spondylitis (AS). After posing 10 questions to 11 experts they have provided evidence and consensus-based ecommendations on exercise in AS.

Biologic Retention in Ankylosing Spondylitis Patients

A study of biologic-naïve patients with ankylosing spondylitis (AS) who started therapy with a tumour necrosis factor inhibitor (TNFi) shows that after 5 years only 46% are still on a TNFi and that some are able to lower the dose over time.

A nationwide Swedish Rheumatology register followed 2590 Bio-naïve AS who started a TNFi between 2006–2015.

Low Serious Infection Risk with Newer Agents in Psoriasis

JAMA Dermatology reports on a comparative cohort study of 107,707 psoriasis patients, finding a decreased risk of serious infections among users of apremilast, etanercept, and ustekinumab when compared with methotrexate.

Skyrizi (risankizumab) FDA Approved for Psoriasis

AbbVie has announced that the US FDA has granted the approval of Skyrizi (risankizumab-rzaa) for the treatment of moderate to severe plaque psoriasis. 

Skyrizi is an interleukin-23 (IL-23) inhibitor that was also recently approved in Canada and Japan. Skyrizi is the third IL-23 inhibitor (behind guselkumab [Tremfya] and tildrakizumab [Ilumya]) to be approved in the last year.

Higher Comorbidities in Hidradenitis Suppurativa

JAMA Dermatology reports that patients with hidradenitis suppurativa have significantly more comorbidities than do patients with psoriasis.

A cross-sectional study compared 5306 HS patients, 14 037 patients with psoriasis, and 1 733 810 controls from electronic health records between 2013 and 2018. Specifically they examined comorbidities using the Charlson Comorbidity Index (CCI) score.