Twenty Years of Clinical Trials in Axial Spondyloarthritis

What Can We Learn for the Future?

Joachim Sieper; Denis Poddubnyy

Disclosures

Curr Opin Rheumatol. 2021;33(4):363-369. 

In This Article

Abstract and Introduction

Abstract

Purpose of Review: We have now about 20 years of experience with the treatment of axial spondyloarthritis with biologics, which raises the question what we can learn from past experience, and which open questions should be addressed in future investigations.

Recent Findings: Many studies have shown that axSpA patients – both patients in their nonradiological and radiological stage – respond similarly well to biologic treatment and these patients should be seen as having the same disease at different stages. AxSpA respond best to TNF-blocker – and probably also to other biologics – if the disease duration is short and if objective parameters of inflammation, such as C-reactive protein or MRI are positive. Primary aim of treatment is to reach and maintain clinical remission. Once remission is achieved, it can be maintained by continuing treatment, and in a proportion of yet not well defined patients the drug dose can be reduced without inducing a flare. The recent demonstration of a good efficacy, in addition to TNF blockers, also of IL-17 inhibitors and JAK-inhibitors in axSpA patients raises the question how to select the best patients for the best treatment. Radiographic progression can best be stopped by effectively suppressing inflammation, whether different drugs have here a different effect has still to be defined. More sensitive measurements of radiographic progression are urgently needed.

Summary: Reaching and maintaining clinical remission and preventing structural bony damage is the primary treatment target in patients with axSpA. How to reach this aim best has to be further explored in the future.

Introduction

When we conducted the first clinical trials in axial spondyloarthritis (axSpA) about 20 years ago only patients who had already reached the stage of ankylosing spondylitis could be included and the only effective treatment available were NSAIDs.[1] However, it soon became clear that tumour necrosis factor (TNF) blockers were very effective in active ankylosing spondylitis patients who had failed previous NSAID treatment and that the anti-TNF-effect was a class effect. This situation raised a few important questions, which had to be answered, which are still valid today also with respect to other biological and targeted synthetic disease modifying anti-rheumatic drugs (bsDMARDs and tsDMARDs) and which will be discussed in Table 1.

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