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Philip Conaghan, MBBS, PhD, discusses his presentation entitled, “Meaningful Improvements in WOMAC Pain and Physical Function in 3 Phase 3 Trials of Tanezumab in Patients With Moderate-to-Severe Osteoarthritis: A Responder Analysis.”
Rheumatology Network sat down with Philip Conaghan, MBBS, PhD, to discuss his World Congress on Osteoporosis, Osteoarthritis, and Musculoskeletal Diseases presentation entitled, “Meaningful Improvements in WOMAC Pain and Physical Function in 3 Phase 3 Trials of Tanezumab in Patients With Moderate-to-Severe Osteoarthritis: A Responder Analysis.” Dr. Conaghan is Professor of Muskuloskeletal Medicine at the University of Leeds. He explains the key takeaway points from his presentation, the study designs of the phase 3 trials, and the clinical significance of these results.
Rheumatology Network: To begin, what are the key takeaway points from your presentation?
Philip Conaghan, MBBS, PhD: I think the key point is we've been used to data coming out about monoclonal antibodies to new growth factor for some time. And questions about its efficacy have been raised at different times, especially as doses were reduced to minimize side effects. So, the key message to come out of this was based on work we've done previously showing that a 1 point, or 15%, improvement in WOMAC pain and in physical function (minimally clinically important differences for patients). We wanted to see how well tanezumab at 2.5 or 5 milligrams, as it was used in trials, how well they performed in achieving those levels of 1 point, or 15%, improvement for both pain and physical function.
RN: What were the study designs of the 3 phase 3 trials?
PC: So, people will be familiar with these trials. There were 2 big trials that were randomized control trials with 3.5 or 5 milligrams versus placebo. And there were 230 to 280 people per arm in those trials. And in the third trial, there was tanezumab 2.5, or 5 verses a non-steroidal anti-inflammatory drug (NSAID), so that's a longer-term trial. The others were shorter term studies with shorter term primary endpoints. The other was a longer-term trial. And it's important to realize it was against an active control. So, it wasn't a placebo-controlled study. So, different design for that. But it still allows us to compare the patients achieving meaningful pain and function response, even though it was an inside comparative trial.
RN: And what were the results of these studies?
PC: What the results showed is that we see significant improvements for the tanezumab 2.5, and 5 milligram groups for both the randomized control trials, or at least for the 2.5, stepping up to 5 at second dose in 1 of those studies. Those patients had significant improvement for people in proportions achieving minimally meaningful improvements. And I've got to be very careful how I say those phrases. So, these are patients achieving minimally meaningful improvements for WOMAC pain and function. So that was for the 2 randomized trials and for the trial against placebo, the proportions of patients, meeting the thresholds to that minimally meaningful improvement for pain and function was similar for tanezumab and NSAIDs. So that's very comforting to those of us who've been using NSAIDs for a long period of time.
RN: Were you surprised by the results of the studies?
PC: Not really, I think for a long time, we've struggled with understanding what's an important difference. Most trials compare group level differences; we try to see how much is in this group versus how much is in the placebo group. And that's often hard to understand between group differences. It's often a bit easier to understand minimal clinically important differences at the individual patient level. And those figures have been around forever. Saying that a 30% change is 1 level of change that patients can recognize. As I said in earlier work, we showed that a 15% change was also probably the minimal, meaningful clinical difference that we could determine. I think the third study I mentioned is actually most reassuring when trying to understand new therapies withdrawn or understand how they compare against their current standard of care. And oral NSAIDs remain our current standard of care.
RN: What is the clinical significance of these results?
PC: I think the important issue is that this drug looks like it's got effective clinical relief for patients in terms of pain and in terms of function. And that's really important for a field like osteoarthritis, where we have so few options and indeed, less options than we had 10 years ago. So, I think we desperately need some new therapies that will work to reduce people's pain.