Therapy evidence for axSpA based on flawed definition of condition, say clinicians


Two post-hoc analyses of ustekinumab in patients with psoriatic arthritis (PsA) with axial symptoms simply do not stand up to scrutiny, two leading rheumatologists have argued.

Writing in the Annals of Rheumatic Diseases, Juergen Braun from Ruhr University BochumHerne, Germany and Robert Landewe from Amsterdam Rheumatology Center, The Netherlands, strongly criticise the use of “physician-reported spondylitis”, in the post-hoc analyses of the PSUMMIT 1 and PSUMMIT 2 trials.

They said this “new diagnosis” has potentially far-reaching consequences and should be abandoned.

In a Viewpoint article they note that “there is a clear marketing incentive” behind the approach which in their view does not use a sound diagnosis of axSpA.

“The unexpected failure of the anti-IL-23 RCTs in axSpA has undoubtedly been a disappointment for the pharmaceutical companies involved, and the suggestion of improvements in a few typical axSpA measures may have incentivised the post-hoc analyses of the PsA trials,” they said.

While the RCTs in question clearly show that ustekinumab works in PsA, the post-hoc analyses are treating patients who say they have back pain when asked and show some signs of disease activity as if they had previously been diagnosed with axSpA, they explain.

What the analyses may be picking up is improvement in back pain as a bystander effect of general improvement in patients who had severe peripheral PsA, with involvement of many joints and skin and a high burden of disease.

“It is well known that pain-spreading mechanisms (central sensitisation) may cause back pain which may improve on improvement in general well-being,” they concluded.

Disease-specific measures such BASDAI and ASDAS, which were used in the analyses, should only be applied in proven axial inflammation as they were developed to do.

“Once axial inflammation of patients with peripheral PsA has been proven, for example, by MRI, BASDAI and ASDAS may be appropriate tools to follow these patients over time, but not before that has been achieved,” they said.

“Far better definitions for axial PsA are needed to be used for inclusion in clinical trials.

“In conclusion, we propose to abandon the term ‘physician-reported spondylitis’. The likelihood that axial PsA is much different from axSpA in terms of treatment response in patients with proven axial inflammation is, in our opinion, rather low.”

Ustekinumab is an IL-12/23 inhibitor that blocks binding to the shared p40 subunit, guselkumab and risankizumab are selective IL-23 inhibitors that block binding to the p19 subunit.

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