Secukinumab, an Interleukin-17A Inhibitor, in Ankylosing Spondylitis


Dominique Baeten, M.D., Joachim Sieper, M.D., Jürgen Braun, M.D., Xenofon Baraliakos, M.D., Maxime Dougados, M.D., Paul Emery, F.R.C.P., Atul Deodhar, M.D., Brian Porter, M.D., Ph.D., M.P.H., Ruvie Martin, Ph.D., Mats Andersson, M.Sc., Shephard Mpofu, M.D., and Hanno B. Richards, M.D. for the MEASURE 1 and MEASURE 2 Study Groups
N Engl J Med 2015; 373:2534-2548December 24, 2015DOI: 10.1056/NEJMoa1505066BACKGROUND
Secukinumab is an anti–interleukin-17A monoclonal antibody that has been shown to control the symptoms of ankylosing spondylitis in a phase 2 trial. We conducted two phase 3 trials of secukinumab in patients with active ankylosing spondylitis.
In two double-blind trials, we randomly assigned patients to receive secukinumab or placebo. In MEASURE 1, a total of 371 patients received intravenous secukinumab (10 mg per kilogram of body weight) or matched placebo at weeks 0, 2, and 4, followed by subcutaneous secukinumab (150 mg or 75 mg) or matched placebo every 4 weeks starting at week 8. In MEASURE 2, a total of 219 patients received subcutaneous secukinumab (150 mg or 75 mg) or matched placebo at baseline; at weeks 1, 2, and 3; and every 4 weeks starting at week 4. At week 16, patients in the placebo group were randomly reassigned to subcutaneous secukinumab at a dose of 150 mg or 75 mg. The primary end point was the proportion of patients with at least 20% improvement in Assessment of Spondyloarthritis International Society (ASAS20) response criteria at week 16.


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Biologics for Rheumatic Diseases


First, we will mention Rheumatoid Arthritis (RA) because the first biologic launched to the market was directed to treat this disease. Multiple factors cause RA, but once the diagnosis is established is crucial to start treating these patients as soon as possible, to induce the remission of the disease. Until the past century in the therapeutic armamentarium we had few drugs to treat RA. All, were chemical compounds like NSAIDS, corticosteroids, gold salts (now withdrawn from the market because of their side effects), hydroxychloroquine, sulfasalazine, leflunomide and Methotrexate (MTX), which, has become the gold standard to treat the disease. However, not all patients (30-50%) respond to these meds and the disease progresses gradually towards a significant disability. Therefore at the end of the twentieth century, the possibility of producing other, more complex drugs was devised. These new drugs are call biologics since they are not chemical formulations,

They are complex proteins, mainly monoclonal antibodies, that block other proteins (called cytokines) involved in inflammation in RA. One of the most prominent pro-inflammatory cytokines is TNF. Therefore, the first biologics were designed to block TNF.

Distintos Biológicos para la AR

Distintos Biológicos para la AR

See below the anti-TNF that are in the pharmaceutical market (in brackets the commercial name)

  • Infliximab, IV administration (Remicade®). Now we have two infliximab-biosimilar products in Europe, and in some other countries called Remsima® and Inflectra® (in another section I will explain what means a biosimilar drug)
  • Etanercept weekly subcutaneous administration (Enbrel®)
  • Adalimumab, biweekly subcutaneous administration (Humira®)
  • Certolizumab, biweekly subcutaneous administration (Cimzia®)
  • Golimumab monthly subcutaneous administration (Simponi®)

Biologics non anti-TNF

Apart TNF, interleukin 6 (IL-6) is another cytokine involved in inflammation. Tocilizumab (RoActemra®) is the first anti-IL-6 approved to treat RA. Tocilizumab is administered IV monthly but recently a subcutaneous formulation has been launched.

Interestingly, a biologic that years ago was used to treat non-Hodgkin lymphoma -Rituximab- was shown to be useful in RA. Rituximab is administered IV at least once every six months. (Mabthera®). This biologic acts against B lymphocytes, which are responsible for producing antibodies.

Finally, another relevant biologic is Abatacept (Orencia®). Abatacept interferes with the contact between the interaction of two types of lymphocytes (T and B) that are essential for the harmful effects of the disease occur. Abatacept has an IV presentation but recently a subcutaneous presentation is in the market.

Ankylosing Spondylitis (AS)

For AS, only anti-TNF have been shown to be effective and have been licensed to treat the disease. Other promising drugs are under development, but it may take a few years to have other biologics to treat this disease

Psoriatic Arthritis PsA

Until recently only anti-TNF had been licensed to treat this disease. Recently, a new non anti-TNF biologic Ustekinumab (Stelara®) has been approved to treat PsA. Ustekinumab was launched first for cutaneous psoriasis, but it took a while to demonstrate that it was also efficacious in PsA.

Tailored anti-TNF-alpha dose successful in patients with AS


Arends S, et al. Clin Exp Rheumatol. 2015;Epub ahead of print

About half of patients with ankylosing spondylitis who had tailored dose-reduction of tumor necrosis factor-alpha blocking agents showed low disease activity after 24 months, according to study findings.

Patient data were gathered from the Groningen Leeuwarden Ankylosing Spondylitis (GLAS) prospective, longitudinal, observational study. Researchers selected 58 patients with ankylosing spondylitis (AS) and stable, low disease activity being treated with a biologic agent. Mean patient age was 45 years, and 91% of the patients were men. Patients were enrolled between June 2005 and March 2011, and median disease duration was 18 years.

Patients began a dose reduction of Enbrel (etanercept, Amgen), infliximab or Humira (adalimumab, AbbVie), at the time of which median Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was 1.5 and Ankylosing Spondylitis Disease Activity Score (ASDAS) was 1.4, down from a mean 5.8 BASDAI and 3.7 ASDAS at the beginning of treatment.

Dose reduction involved tapering the dose and/or extending the interval between doses, as well as tailoring the dose individually to the patient based on BASDAI score and physician and patient preferences.

After 6, 12, 18 and 24 months, 43, 36, 33, and 31 patients, respectively, remained on the reduced dose. Of the 31 patients who continued at a reduced dose, 21 remained on the same initial reduced dose, according to the researchers. Four patients attempted to further reduce the dose but returned to the initial reduced dose, and two increased dosage frequency without returning to the conventional dose. Mean dose of therapy after 24 months was 62% of the conventional dosage.

The only predictors of response to treatment with a lower dose was higher AS quality-of-life scores prior to reduction, according to the researchers. by Shirley Pulawski

Disclosures: Arends reports the receipt of research grants from Abbott, Pfizer and Wyeth. Please see the full study for a complete list of all other authors’ financial disclosures