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FUTURE shines bright for secukinumab in psoriatic arthritis

Audrey Abella
24 Apr 2020

The phase III FUTURE 2 trial has shown the ability of the bDMARD*, interleukin(IL)-17A inhibitor secukinumab to provide sustained improvements across multiple clinical domains in patients with psoriatic arthritis (PsA) with consistent safety over 5 years.

“PsA is a lifelong condition, requiring access to durable therapeutic agents. Early diagnosis and assessment of disease severity is important for timely treatment initiation, leading to sustained long-term therapeutic benefit and quality of life (QoL),” said the researchers. [Clin Exp Rheumatol 2008;26:S62-S65; Rheum Dis Clin North Am 2012;38:373-386]

“[Our initial findings revealed that] secukinumab 150 and 300 mg offered sustained and clinically meaningful improvements in joint and skin symptoms, physical function, and QoL in patients with active PsA over 2 years,” said the researchers. [Lancet 2015;386:1137-1146; Rheumatology 2017;56:1993-2003] The current findings confirm the clinical benefit and safety of long-term IL-17A inhibition in this setting, they added.

A total of 397 participants (65 percent TNFi**-naïve, 47 percent receiving concomitant methotrexate) were randomized 1:1:1:1 to receive secukinumab 75, 150, or 300 mg, or placebo weekly from baseline and then Q4W from week 4. Secukinumab dose was increased (from 150 to 300 mg; from 75 to 150 or 300 mg) from week 128 or if active signs of disease were observed. The escalated dose was maintained thereafter. Sixty-two percent completed 5 years of treatment. [Lancet Rheumatol 2020;2:e227-235]

At 5 years, ACR20/50*** responses were similar in the secukinumab 150- and 300-mg arms (79/46 percent [150 mg] and 74/48 percent [300 mg]). These responses were sustained regardless of baseline methotrexate use (74/47 percent and 63/38 percent, respectively).

The improvements with secukinumab were also sustained through 5 years regardless of TNFi history, with better responses among TNFi-naïve patients than those exhibiting intolerance or insufficient response to TNFis, said the researchers. “[T]herefore, IL-17A inhibitors deserve consideration for earlier use in the treatment paradigm.”

Taken together, these results provide reassurance that long-term treatment with secukinumab provides sustained efficacy for PsA patients who are either naïve, intolerant, or had an inadequate response to TNFis, said the researchers.

ACR20/50 responses were also sustained among secukinumab 150-mg recipients who increased their dose (from 75/45 percent [week 128] to 71/41 percent [week 260]). The Sankey-style overlay analysis also revealed that more patients had improved ACR responses following dose escalation. “[These highlight] the potential benefit of dose escalation from 150 to 300 mg in patients with suboptimal response to secukinumab 150 mg,” noted the researchers.

The discontinuation rate among secukinumab 150/300 mg recipients was 35 percent, which mirrored the rates reported in other PsA trials. [Ann Rheum Dis 2014;73:1689-1694; Clin Rheumatol 2018;37:3285-3296] With no new or unexpected safety signals reported, these findings underscore the consistent and satisfactory safety profile of secukinumab.

 

Taking the IL-17 route

“The IL-17 pathway is crucial in the pathogenesis of PsA,” said the researchers. As such, the EULAR#, GRAPPA##, ACR, and National Psoriasis Foundation recommend IL-17A inhibitors as first-line treatment option following TNFi treatment to manage the various clinical manifestations### of PsA. [Ann Rheum Dis 2016;75:499-510; Arthritis Rheumatol 2016;68:1060-1071; Arthritis Care Res 2019;71:2-29]

Evaluating the long-term efficacy, safety, and tolerability of biologics is important given the chronic nature of PsA. [RMD Open 2018;4:e000596] The current findings add to the growing evidence on IL-17 inhibition in PsA. Collectively, these data may help guide physicians in their treatment decisions to better manage patients presenting with different manifestations of PsA, noted the researchers.

The 1-year results of a head-to-head trial (secukinumab vs adalimumab) in PsA shall be reported in the future, they added.

 

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Most Read Articles
Roshini Claire Anthony, 29 May 2020

For coffee drinkers, drinking filtered coffee may be tied to a lower mortality risk, including cardiovascular disease (CVD)-related mortality, a study from Norway suggested.

5 days ago
Use of corticosteroid is not associated with improved outcomes in idiopathic pulmonary fibrosis (IPF) patients admitted to the hospital with acute exacerbation (AE), reveals a recent study. In addition, corticosteroids may even contribute to reduced overall survival following exacerbation.
Dr. Wong Soon Tee, 28 May 2020
Acne is a common skin problem seen in primary care. Dr Wong Soon Tee of Assurance Skin Clinic at Mt Elizabeth Novena Hospital, Singapore shares his insights with Pearl Toh on how to manage acne in the primary care setting.
27 May 2020
The perception that proton pump inhibitors (PPIs) cause multiple serious adverse effects (AEs) is supported by many internists, who then recommend treatment cessation even in patients at high risk for upper gastrointestinal bleeding (UGIB), reveals a study.