Secukinumab as a Treatment Option in PsA

Two studies published in leading medical journals show that secukinumab, a human monoclonal antibody used to treat psoriasis, could also be a potential treatment option for patients with psoriatic arthritis.

The reports, one in the New England Journal of Medicine and the other in The Lancet, show promising results for secukinumab in patients with psoriatic arthritis.

The search for new treatment options in psoriatic arthritis has been instilled with new vigor in recent months. The Lancet recently published a series of articles on issues ranging from treat-to-target to the role of interleukin-17 as a pathway for new treatments for psoriatic arthritis. Clinical trials are underway to assess the efficacy of secukinumab and ixekizumab for psoriatic arthritis. 

Continued research is necessary, writes Philip J. Mease, M.D., and colleagues in the Oct. 1 article in the

New England Journal of Medicine,

because even though inhibitors of tumor necrosis factors (TNF) have improved outcomes for some patients with psoriatic arthitis, not all patients respond to this treatment and others have had adverse effects.  "Effective therapies with a different mechanism of action are needed. Interleukin-17-a is postulated to play a role in the pathogenesis of psoriatic arthritis. Increased levels of cells that produce interleukin-17-a are found in the circulation, joints, and skin plaques of patients with psoriatic arthritis, and these levels have been shown to correlate with measures of disease activity and structural damage," the authors wrote. 

The NEJM article

shows that secukinumab was more effective than placebo in patients with psoriatic arthritis, which validates interleukin-17-a as a therapeutic target. But the study – with only 606 patients – was too small and too short to evaluate uncommon serious adverse events and risks associated with long-term use, the researchers cautioned. Mease, of Seattle Rheumatology Associates in Seattle, conducted a double-blind, phase III study of 606 patients with psoriatic arthritis. The patients were randomly assigned in a 1:1:1 ratio to receive intravenous secukinumab (at a dose of 10 mg per kilogram) at weeks 0, 2, and 4, followed by subcutaneous secukinumab at a dose of either 150 mg or 75 mg every 4 weeks, or placebo. Patients in the placebo group were switched to subcutaneous secukinumab at a dose of 150 mg or 75 mg at week 16 or 24, depending on clinical response. The primary end point was the proportion of patients with an American College of Rheumatology 20 (ACR20) response at week 24, defined as a 20% improvement from baseline in the number of tender and swollen joints and at least three other important domains, the authors wrote in the study. 

The Lancet study

, published in the Sept. 25 issue, evaluated the use of subcutaneous secukinumab for treating symptoms associated with psoriatic arthritis. Led by Iain B. McInnes, MD, of University of Glasgow in the UK, researchers found that 300 mg and 150 mg was enough to improve the signs and symptoms of psoriatic arthritis, suggesting that “secukinumab is a potential future treatment option for patients with this disorder.” This was a phase III, double-blind, placebo-controlled study of patients from 76 treatment centers in Asia, Australia, Canada, Europe and the United States. The findings as reported in

The Lancet

:  “Between April 14, and Nov 25, 2013, 397 patients were randomly assigned to receive secukinumab 300 mg (n=100), 150 mg (n=100), 75 mg (n=99), or placebo (n=98). A significantly higher proportion of patients achieved an ACR20 at week 24 with secukinumab 300 mg (54 [54%] patients; odds ratio versus placebo 6•81, 95% CI 3•42–13•56; p<0•0001), 150 mg (51 [51%] patients; 6•52, 3•25–13•08; p<0•0001), and 75 mg (29 [29%] patients; 2•32, 1•14–4•73; p=0•0399) versus placebo (15 [15%] patients). Up to week 16, the most common adverse events were upper respiratory tract infections (four [4%], eight [8%], ten [10%], and seven [7%] with secukinumab 300 mg, 150 mg, 75 mg, and placebo, respectively) and nasopharyngitis (six [6%], four [4%], six [6%], and eight [8%], respectively). Serious adverse events were reported by five (5%), one (1%), and four (4%) patients in the secukinumab 300 mg, 150 mg, and 75 mg groups, respectively, compared with two (2%) in the placebo group.” The emergence of effective treatments for inflammatory arthritis have led to the development of a new concept in treat-to-target treatments, wrote Dafna Gladman of the University of Toronto, in a

review

of a

study

published in the Sept. 30 issue of 

The Lancet.

 She described treat-to-target as “a treatment strategy in which the clinician treats the patient aggressively enough to reach and maintain specified and sequentially measured goals, such as remission or low disease activity. A proactive clear endpoint, which is the aim of the treatment, should be used as a specific target algorithm. This endpoint should be supported by findings from randomized controlled trials which suggest that early aggressive treatment approaches are advantageous.” Early intervention and tight control of inflammation has been shown to optimize outcomes in rheumatoid arthritis, but it hasn’t yet been studied in psoriatic arthritis.  

The Lancet

article

 focuses on an open-label multicenter controlled trial by Phillip S. Helliwell, MD, and colleagues of the University of Leeds in the UK. Researchers followed 206 patients with early psoriatic arthritis who were diagnosed, but not yet treated for the disease. They observed the patients between May 2008 and March 21, 2012. 101 patients received tight control and 105 received standard care. The researchers suggest that the “tight control of psoriatic arthritis disease activity through a treat-to-target approach significantly improves joint outcomes for newly diagnosed patients, with no unexpected serious adverse events reported.”  “In the intention-to-treat patient population, the odds of achieving an ACR20 response at 48 weeks were higher in the tight control group than in the standard care group (odds ratio 1•91, 95% CI 1•03–3•55; p=0•0392). Serious adverse events were reported by 20 (10%) patients (25 events in 14 [14%] patients in the tight control group and eight events in six [6%] patients in the standard care group) during the course of the study. No unexpected serious adverse events or deaths occurred,” the authors wrote in the study.   

References:

Mease PJ, McInnes IB, et al.

"Secukinumab Inhibition of Interleukin-17A in Patients with Psoriatic Arthritis,"

New England Journal of Medicine.

October 1, 2015. DOI: 10.1056/NEJMoa1412679 McInnes IB, Mease PJ, et al.

"Secukinumab, a human anti-interleukin-17A monoclonal antibody, in patients with psoriatic arthritis (FUTURE 2): a randomised, double-blind, placebo-controlled, phase 3 trial,"

The Lancet.

Published Online: 28 June 2015. DOI: http://dx.doi.org/10.1016/S0140-6736(15)61134-5 Dafna D Gladman.

"Is it time for treat to target in psoriatic arthritis?"

The Lancet

. Published Online: 30 September 2015. DOI: http://dx.doi.org/10.1016/S0140-6736(15)00348-7 Coates LC, Moverley AR, et al.

"Effect of tight control of inflammation in early psoriatic arthritis (TICOPA): a UK multicentre, open-label, randomised controlled trial,"

The Lancet

. Published Online: 30 September 2015. DOI: http://dx.doi.org/10.1016/S0140-6736(15)00347-5