Psoriatic arthritis: Beyond TNF inhibition

Psoriatic arthritis: Beyond TNF inhibition

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By Dr Irwin Lim, Rheumatologist

The 9th International Congress of Spondyloarthropathies just took place in Ghent, Belgium.

Ghent, BelgiumWorld experts, both clinical and basic researchers working in the field of spondyloarthritis (that includes psoriatic arthritis and ankylosing spondylitis) congregate to share and update each other every 2 years.

As a clinician in private practice, rather than an academic or scientist, I would be in the minority attending such a meeting (read my reflections from the 8th Congress here). A lot of the basic science is difficult for me to absorb but there's always still so much to learn and to contemplate.

With this blog's audience in mind, I thought I'd write about a clear theme that has evolved over the last 4-5 years.

For too long, psoriatic arthritis (PsA) has really been managed in the same ways as rheumatoid arthritis (RA), eventhough RA & PsA can be so distinct in the way they present, the different tissues they affect, and the genetic susceptibility.

The medication therapy of PsA borrows so much from RA.

Methotrexate is still the drug most rheumatologists would use. In addition, we use Sulphasalazine and Leflunomide as traditional disease-modifying agents (DMARDs).

And when these traditional DMARDs aren't effective enough, we can then use TNF-inhibitor therapy.

These agents are effective and they have proven to be a significant advance for those with Psoriasis (Ps) and PsA over the last decade or so, but there's still a number of unmet needs:

  • A significant number of PsA patients have to switch using the medication over the years, through loss of effect or a side effect (as shown by DANBIO registry data)
  • Some patients get good skin response but their joints do not improve, or they get good joint disease improvement while the skin remains problematic. In some, the skin disease may paradoxically become more of a problem.
  • TNF inhibitors seem more effective for enthesitis, dactylitis, and nail disease compared with the traditional DMARDs, but there's still room for improvement
  • When clinicians talk about effective medications, we mean that they reduce the extent of disease, and reduce the symptoms and signs, and thereby, how patients function in their day-to-day activities. What patients want is a cure. And we don't have that yet with PsA.

To date, if you have PsA, and are in the group where TNF inhibitor therapy does not prove effective, there aren't other good options.

That's about to change.

The TNF pathway, a series of chemical signals involved in the immune process, is definitely disordered in Ps and PsA. This is why interfering and inhibiting this pathway does help.

But, our immune system is obviously very much more complicated and dependent on many other chemical pathways and signals.

Well, it has become increasingly clear that the IL23/IL17 pathway is critical in Ps and PsA. This is a point of differentiation between the spondyloarthropathies and RA.

This IL23/IL17 pathway is also complicated, with series of signals regulating a whole host of different chemicals involved in the immune process. It is the imbalance or the overamplification of these signals which lead to disease.

There are now numerous attempts to rein in this imbalance by targeting different components of this IL23/IL17 axis, at multiple sites both upstream and downstream. These include:

  • Ustekinumab, which blocks the p40 subunit molecule, then affecting IL12 and IL23
  • Secukinumab, an IL17A inhibitor
  • Brodalumab, which blocks the IL17A receptor
  • a number of dedicated IL23 inhibitors
  • a combination antibody that can block both TNF & IL17
  • And many others....

Results have been very encouraging.

I wanted to give those of you with PsA which may not be as controlled as we would like, cause for optimism. The future does look bright.

Dr Irwin Lim is a rheumatologist and a director of BJC Health. You should follow him on twitter here

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