The window of opportunity: a relevant concept for axial spondyloarthritis
The window of opportunity is a relatively new but very important and relevant concept especially to patients. It postulates that, for a particular disease, there exists a limited period from the onset of symptoms, wherein aggressive treatment to annihilate inflammation to comprehensively put the disease into full remission can prevent damage and future disability, and possibly eventual drug-free remission (aka cure) in some.
This concept was first propounded in RA, and subsequently proven. The window in RA is 3-6 months from symptom onset. This has led to a therapeutic move towards front-loading aggressive and effective targeted therapies to capitalise on this window.
This concept in AS is now under intense scrutiny, and early evidence has emerged to suggest that such a window indeed exists in AS. The goal (and outcome measure) is twofold, pertaining to the 2 aspects of AS disease activity: inflammation (spondylitis) causing pain and damage, and new bone formation (ankylosis) causing disability. Between the 2, ankylosis is the greater concern and tougher nut to crack.
Today, we consider the question, “How early to treat?”. One observational study suggests that the damage and ankylosis progresses slowly in the first 5 years. But that doesn’t mean that starting treatment at Year 5 can prevent eventual ankylosis. Other studies suggest the window to be 1-3 years from symptom onset. In fact, there is evidence that early joint and bone damage can even be “backfilled” (ie attempts at repair) within this window, with a mere 3 months of anti-TNF treatment.
There are reasons for hope in AS now.
Radiographic progression in axial spondyloarthritis moves slowly in first 5 years
Early ankylosing spondylitis treatment stops transition from inflammatory to bone-forming fatty lesions
Evaluation of the change in structural radiographic sacroiliac joint damage after 2 years of etanercept therapy (EMBARK trial) in comparison to a contemporary control cohort (DESIR cohort) in recent onset axial spondyloarthritis
In the EMBARK trial, 2 years’ use of Etanercept in AS patients with disease duration averaging 2.4 years resulted in far less damage progression compared to a control cohort with disease duration averaging 1.5 years. There were even hints of “backfill” of lesions (ie repair) in the Etanercept treated cohort.
Modification of structural lesions on MRI of the sacroiliac joints by etanercept in the EMBARK trial: a 12-week randomised placebo-controlled trial in patients with non-radiographic axial spondyloarthritis
Even with a short 12 weeks of treatment with Etanercept in early non-radiographic AxSpA (average duration of 2.4 years from symptom onset), erosions were reduced and “backfilled” (early attempts at repair).