Medicine Matters rheumatology

The NORD-STAR study is an investigator-initiated trial, where we actually wanted to compare head-to-head different modes of action in biological drugs, in the treatment of early RA. And also compare these three biological drugs with a conventional, active treatment. In this study, we had four treatment arms.

The patients were randomized in an open-label design to either a conventional treatment, with methotrexate in combination with glucocorticoids or one of three biological treatments. One was a TNF inhibitor, namely certolizumab pegol. The other was a abatacept, and the third one was an IL-6 inhibitor, namely tocilizumab. The main finding there were actually several.

And I think that a very important finding was that even in the active conventional therapy group, which was the patients who were randomized to a combination of methotrexate, and glucocorticoids, that that group achieved remission rates that were at the same level as those patients who received one of the three biological drugs. So all patients, in all four arms, the remission rates were above 40%, which is very convincing when we look at CDAI remission, which was the case in this study.

Furthermore, when we looked at differences across the different-- in the responses across the treatments, we found that there were some differences, but they were modest in nature. It was actually so that the abatacept arm was the arm that performed the best. It was actually slightly superior to the others when it came to CDAI remission, but not when it came to the other remission criteria.

So there was very good responses in all treatment arms, but no clear winner, if you can say so. So these were data after 24 weeks, and we are then looking forward also to see the radiographic data at 48 weeks. It stresses the importance of having an active conventional therapy as the initial treatment for early RA, that you should start out with methotrexate in high doses. We used 25 milligrams in this study, and that methotrexate should be combined with glucocorticoids in the initial weeks, or one or two months off the treatment, while you await the impact of methotrexate to take place.

So the bridging therapy with glucocorticoids is very important. Then you can rapidly taper, and you will be out of steroids when you come to these 24 weeks. But in the initial phase, it's very important in our window of opportunity to actually include the glucocorticoids. They help you to achieve remission, and help you probably also to reach these high remission rates that we had here.

After the 48 weeks, the study protocol says that those patients who then go into prolonged remission, they are then re-randomized into two different de-escalation strategies. So we will also investigate how these patients actually do when we then de-escalate the biological treatments. And in addition, we have bio-banking in the patients, so that we also plan to see if we can identify biomarkers that can help us tailor the treatment and see which patients is that benefit the most from these different biological treatments.