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

Tony Sampson, Mercer University College of Pharmacy

It is suggested that psoriatic arthritis is a chronic inflammatory autoimmune disease that targets both skin and nail and affects approximately 0.005 percent of the general population. [1]

According to The American College of Rheumatology, current treatment for psoriatic arthritis includes non steroidal anti-inflammatory drugs, disease modifying anti-rheumatic drugs, hydroxychloroquine, azathioprine, and anti-tumor necrosis factor drugs. [2]

Title: Secukinumab Inhibition of Interleukin-17A in Patients with Psoriatic Arthritis
Design Multicenter, randomized, double-blinded, phase III, placebo-controlled trial; N= 606
Objective To evaluate the efficacy and safety of secukinumab, an anti-interleukin-17A monoclonal antibody in patients with psoriatic arthritis
Study Groups Secukinumab 150 mg (n= 202), secukinumab 75 mg (n= 202), placebo (n= 202)
Methods Patients were randomized in a 1:1:1 ratio to receive either intravenous secukinumab 10 mg/kg intravenously at weeks zero, two, and four followed by secukinumab 150 mg or 75 mg subcutaneously every four weeks or placebo.  Patients in the placebo group were switched to subcutaneous secukinumab 150 mg or 75 mg at week sixteen or twenty-four depending on clinical response.   Improvement was measured by the American College of Rheumatology 20 (ACR20) response which was defined as 20% improvement from baseline in the number of tender and swollen joints and at least three other important domains.
Duration From September 2011 to October 2012
Primary Outcome Measure The proportion of patients with an ACR20 response at week 24
Baseline Characteristics Characteristics Secukinumab 150 mg (n= 202) Secukinumab 75 mg (n= 202) Placebo (n= 202)
Age –yr 49.6 ± 11.8 48.8 ± 12.2 48.5 ± 11.2
Female sex—no.(%) 106 (52.5) 118 (58.4) 106 (52.5)
Race—no. (%)
White 162 (80.2) 165 (81.7) 154 (76.2)
Black 3 (1.5) 2 (1.0) 0
Asian 36 (17.8) 33 (16.3) 46 (22.8)
Other 1 (0.5) 1 (0.5) 2 (1)=.0)
Psoriasis affecting ³ 3% of body-surface area—no. (%) 108 (53.5) 108 (53.5) 109 (54.0)
Results ACR20 response rate at week 24 was 50% for secukinumab 150 mg group, 50.5% for the secukinumab 75 mg group and 17.3% in placebo (p< 0.001).
Adverse Events Common Adverse Events:

Secukinumab 150 mg: Nasopharyngitis (9.4%), headaches (5.4%), upper respiratory tract infection (6.4%), hypercholesterolemia (3.0%)

Secukinumab 75 mg: Nasopharyngitis (6.9%), headache (5.4%), upper respiratory tract infection (4.5%), hypercholesterolemia (4.0%)

Placebo: Nasopharyngitis (4.5%), headache (5.4%), upper respiratory tract infection (5.4%), hypercholesterolemia (3.5%)

Serious Adverse Events:

Secukinumanb 75 mg: cardiac disorders (1.2%), nervous system disorders (1.4%)

Secukinumab 150 mg: cardiac disorders (1.1%), nervous system disorder (0.6%)

Percentage that Discontinued due to Adverse Events:

Secukinumab 150 mg (1.5%), secukinumab 75 mg (2.0%), placebo (1.7%)

Study Author Conclusions Secukinumab was more effective than placebo in patients with psoriatic arthritis, which validates interleukin-17A as a therapeutic target. Infections were more common in the secukinumab groups than in the placebo group.

The results of this study showed that secukinumab was able to achieve an ACR20 response at week 24 at a higher rate compared to placebo. One limitation of this study was that the placebo controlled period was short so long-term safety and efficacy could not be discovered.    In conclusion, more studies are needed to prove if interleukin-17A inhibitors have a role in treatment of psoriatic arthritis.

References

  1. Hueber AJ, Mcinnes IB. Immune regulation in psoriasis and psoriatic arthritis–recent developments. Immunol Lett. 2007;114(2):59-65.
  2. Rheumatology.org. Psoriatic Arthritis. 2013. Available at: http://www.rheumatology.org/I-Am-A/Patient-Caregiver/Diseases-Conditions/Psoriatic-Arthritis. Accessed October 3, 2015.
  3. Mease PJ, Mcinnes IB, Kirkham B, et al. Secukinumab Inhibition of Interleukin-17A in Patients with Psoriatic Arthritis. N Engl J Med. 2015;373(14):1329-39.
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