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I think so, at least we have some evidence that it exists. This is really an intriguing disease, a disease maybe with two phases. So, in the first days, weeks, months, nobody knows exactly how long that period takes, but the systemic inflammation predominates, I would say, and this is driven by at least some specific cytokines, and the cytokines that are most probably increased in these pathways are IL-1 and IL-6. Both can now be targeted by drugs for blocking the IL-1 pathway. We have not only the short-acting IL-1 receptor antagonist, anakinra, but also the long-acting IL-1 beta blocking antibody, canakinumab. Both are registered in Europe and also for canakinumab in the United States, but also, we have the IL-6 blocking receptor tocilizumab registered in Europe (Fautrel, 2024; Ilaris (canakinumab) SmPC; Ilaris (canakinumab) US PI; Kineret (anakinra) SmPC; RoActemra (tocilizumab) SmPC).

So, we have multiple pathways actually that we can block efficiently, and it really has improved the treatment responses magnificently in the past 10 years. So actually, this also exemplifies the over activation of these pathways that the disease mechanisms early in the disease are really more in the innate immune system than in the adaptive immune system. While if you, on the long term, if you have sustained inflammation over a longer period of time, this also affects many of the disease mechanisms that fall under the adaptive immune system. And this is where we think the concept of the window of opportunity really resides in. So, if you are able to block the disease and to control the disease early on, you prevent the stimulation and the activation actually of the more adaptive immune system (Bindoli & Baggio, 2024; Vastert, 2024).