Psoriatic Arthritis & Ankylosing Spondylitis: Should we target IL-17 or TNF inhibition?

Psoriatic Arthritis & Ankylosing Spondylitis: Should we target IL-17 or TNF inhibition?

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I'm currently in Ghent, Belgium attending the 10th International Congress on Spondyloarthritides. It's a charming place to listen to world experts discussing science.

Just prior to flying here, I was informed that we'll very soon be able to prescribe Secukinumab in Australia with the medication being heavily subsidised by our government.

This is great news as it gives us another option for treating Ankylosing Spondylitis and Psoriatic Arthritis, spondyloarthritides in which we've only had the option of TNF inhibitor medications as biologic DMARDs until this year.

In psoriatic arthritis, we were allowed the option of prescribing Ustekinumab (an IL12/23 blocker) in May. In rheumatoid arthritis, we have a range of different classes of biologic DMARD medications to choose from.

TNF inhibitor medications have been available for use in ankylosing spondylitis and psoriatic arthritis in Australia since 2004. For those not doing well enough on whichever TNF inhibitor therapy they were using, the options have been to add different conventional oral DMARDs (eg Sulphasalazine or Methotrexate), to add different anti-inflammatory medications (NSAIDs or Cox-2 inhibitors or steroids), to swap between the different TNF inhibitor medications (i.e. swapping within the same class of drugs), or to accept the situation.

Secukinumab works via a different mechanism of action compared to the TNF inhibitors. Secukinumab inhibits IL-17A, and in so doing, it works on blocking the IL23/Th17 pathway that is shown to be really important in spondyloarthritis.

There has been a lot of basic science as well as translational studies being presented at this conference on this IL23/Th17 pathway.

With this knowledge (growing yet incomplete) and with the availability of choice, the obvious question that faces the clinician and the patients we treat:

In spondyloarthritis, should we target IL-17 or TNF inhibition?

Some issues to be considered and/or resolved to help answer this are:

  • What is the long term efficacy and safety of IL17 inhibition? Is Secukinumab safer?The surveillance of people on this medication is only a few years at this stage versus the 1.5 decades of widespread TNF inhibitor use. Long term safety data is needed. There will be useful differences in side effect profiles that will be borne out in time.

  • We would like a direct comparison with TNF-inhibitors. A head-to-head trial comparing Secukinumab to a TNF-inhibitor would help. Preferably to show which is more effective in reducing symptoms and in improving quality of life, the stuff patients are most concerned with.

  • Can we actually pick and choose which patient, with which specific manifestations, will respond better to which medication? Patients with spondyloarthritis, and particularly, with psoriatic arthritis can present in many, different ways. Not every treatment helps every aspect of the disease in the same way. For example, monoclonal antibody TNF inhibitors (eg Adalimumab) are effective in treating inflammatory bowel disease but Secukinumab is not.

  • Usefulness in treating uveitis? The monoclonal antibody TNF inhibitors treat and prevent this but there is not data for Secukinumab.

  • Data for reduction in cardiovascular risks?

  • Data for effect on osteoporosis?

  • Is one better than the other for preventing further radiographic damage? There is some early but inconclusive evidence of Secukinumab being very effective in preventing further X-ray damage in ankylosing spondylitis.

    Options are good. I look forward to being able to use Secukinumab, to gain experience with it, and to try and find a qualified answer to the question posed.

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