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Medicine Matters rheumatology

So I think the aim of the control study was to move on from recent studies that we've seen that have already shown that TNF inhibitors are superior to methotrexate in head-to-head trials, but to think about how we use that information and when we use the different drugs in a treatment strategy.

So this trial was a bit different to a straight head-to-head trial of the two drugs. We took patients who had inadequate disease control despite already being on a dose of methotrexate, so a moderate dose, like 15 milligrams. And then they were randomized either to add in the adalimumab or to have their methotrexate escalated. Really to get an idea of when we should intervene, how long we should try on methotrexate, whether higher doses are beneficial, to try and inform the treatment strategy in psoriatic arthritis.

The main findings of the control study were that there is a significantly higher chance of achieving minimal disease activity at 16 weeks with the addition of adalimumab compared to methotrexate, and that was consistent across the different analysis methods used.

It was also found that when you look at the individual components of MDA, all of those are superior with adalimumab compared to methotrexate. So it's not just one element of the disease, you're getting better control across those different elements.

And we did stratify the patients for those who'd been on methotrexate more than three months before the study started, and those who'd been on methotrexate less than three months. And added to map was superior to both of the methotrexate groups, but it did appear that you got a slightly better response with those who'd been on methotrexate for longer, which I think is reflective of the fact that MDA is quite a hard target to hit, so it may take a little bit longer with higher doses of methotrexate to be able to achieve such an outcome.

So I think studies like these are really important when we think about how to treat people with psoriatic arthritis. We're lucky in that recent years, we've had more and more drugs available, so we have much more choice. But there's still very little evidence that helps us to decide how to treat people, what drugs to use in what order, and whether there is a benefit to escalating methotrexate for example, versus just deciding that methotrexate has not worked and we should move on to a more highly effective therapy.

So I think trials like these, strategy studies, are really sorely needed. And I think if we have more treatment strategy trials, that will help us get the best treatment to each patient when they need it.

So obviously, when we have a study like this it uses one particular drug, and it's not clear whether that's extrapolatable to similar classes, or even to different classes of biologics. So I think we don't know for sure whether this is relevant to other drugs or not. I suspect from previous data we've seen, for example, with the etanercept SEAM study that etanercept was superior to methotrexate in a head-to-head trial.

And I think how we use the different biologics is a really important part of the treatment strategy. Choosing the right biologic for the right patient, and thinking about switching between modes of action in the case of non-response. So I think there's a lot more we need to learn moving forwards about using the different biologics in psoriatic arthritis.

So I think obviously, we will see more and more new drugs for psoriatic arthritis. We know that there's a good pipeline coming, and that's really relevant. But I think where we're starting to think about these treatment strategy trials, we really need to think about the questions that we have every day in clinic.

And are these kinds of studies relevant to patients with oligoarthritis? Should we think about other the DMARDs. For example, in the UK, we have to fail at least two standard DMARDs before our patients have access to biologics, but that's not the case in many countries.

And then when we're thinking about biologics, which biologic is best for each individual? Can we personalize it based on the involvement of disease in different domains? Are some drugs better for enthesitis? For skin, we know there's a difference in some of the head-to-head trials thinking about the involvement of axial disease.

So I think moving forward, we really need trials starting to try and personalize therapy to the individual.