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On this month's episode of Overdrive, Rheumatology Network interviewed Terence Rooney, MD, to discuss the findings of a network meta-analysis that examined the efficacy of guselkumab (TREMFYA) for skin clearance and joint improvements in patients with psoriatic arthritis.
A network meta-analysis, using data from 33 Phase 3 randomized clinical trials of active psoriatic arthritis (PsA) therapies, showed guselkumab (TREMFYA) achieved the highest results for skin clearance and showed positive joint efficacy.
Terence Rooney, MD, is the Vice President, Rheumatology and Maternal-Fetal Immunology Disease Area Leader at Janssen Research & Development, LLC.
Read the transcript below:
Terence Rooney, MD: There are 3 key points I'd be looking to share. One about psoriatic arthritis. So psoriatic arthritis is a disease that, despite a lot of treatment advances over the last couple of decades, still struggles with a substantial proportion of patients not reaching the desired target, which is remission and great control of their disease. It's a complex disorder that affects the skin, the joints, and the spine. So, we're looking at the effectiveness of a treatment and relative effectiveness of different treatments for psoriatic arthritis, which I'll abbreviate to PsA from here. It's important to look at each of those 3 things (the skin, the joints, and the spine).
The second point is about the study that was shared at Maui Dermatology. It was the results of a comprehensive Network Meta-Analysis across clinical trials in psoriatic arthritis. In fact, it's the most comprehensive Network Meta-Analysis conducted to date in this disease. It looked at 33 phase 3 clinical trials, 15 different targeted therapies for psoriatic arthritis, and 23 different treatment regimens. Now, Network Meta-Analyses are not a substitute for direct head-to-head randomized controlled clinical trials. But they are a widely well-regarded methodology used by regulators, by health technology bodies, and by guidelines committees, for pulling together, rigorously and systematically, data across multiple clinical trials and forming the best possible picture of the relative performance of different therapies.
My last point to get across is the findings of the Network Meta-Analysis that were they were shared at Maui Dermatology. In summary, TREMFYA is a first in class interleukin 23 inhibitor, ranked first among assessed treatments for skin efficacy with respect to psoriasis and psoriatic elements of psoriatic arthritis. With respect to joints TREMFYA was generally comparable to most other advanced targeted therapies for signs and symptoms of inflammatory joint disease. And when it came to inhibition of progressive radiographic joint damage, an important aspect of the joint disease in PsA, TREMFYA again achieved improvements that were comparable to most treatments, but did rank more highly than risankizumab and upadacitinib, 2 recent entrants to the field. This particular meta-analysis builds on an NMA that was published last year in the Journal of Rheumatology by adding more recent data. That includes data from a more recent phase 3B clinical trial of TREMFYA and PsA that was called COSMOS and adding data from those 2 more recent entrants, the IL-23 inhibitors risankizumab and the Janus kinase inhibitor, upadacitinib. So overall, the results really, I think, illustrate the potential value of NMAs in pulling together results rigorously and systematically across multiple clinical trials of different diseases. And we think it will add to the body of important information that people have when they're making decisions about treatment of this complex disease.
Rheumatology Network: Can you tell me a little bit more about the study design of the Network Meta-Analysis that was presented?
TR: It involved 15 Different targeted therapies. These are the treatments that have been developed over the last 20 years based on an understanding of the biology of these diseases, and specifically targeted aspects of biology that are known or believed to be important in driving signs and symptoms and other features of the disease. And it pulled together from those 15 targeted therapies that included TREMFYA, the interleukin 23 inhibitor, guselkumab, from 33 different randomized clinical trials evaluating 23 different regimens. And there's a rigorous and systematic way to put that information together in a way that controls for differences between trials. For example, different trials may have slightly different placebo response rates for the same outcome measure at the same time point. So NMA adjusts for those differences, and then puts together a ranking of how the different treatments performed on similar outcome measures. And the outcome measures that were looked at in this study are those that are important for people struggling with PsA, so skin disease and joint disease.
As part of joint disease, it includes 2 important dimensions. The first is signs and symptoms. And there are standard outcome measures used to evaluate signs and symptoms of joint disease in these clinical trials, one of which are the American College of Rheumatology (ACR) response criteria. And the second important dimension of joint disease is damage to joints, as measured by X-rays. Inflammatory joint diseases, like psoriatic arthritis, not only cause inflammation within the joints, which makes the joints angry and painful, that can be reversed. But over time, that inflammation of the inner lining of the joints can permanently damage the structural aspects of the joint, which can result in permanent deformity and disability. So, it's really important that these treatments not only improve the swollen, painful joints, but they also prevent that long-term damage. All of those all of those important dimensions were looked at in the in the NMA.
RN: You briefly touched on the findings of the NMA, can you go into some more detail about the precise findings?
TR: In the in the meta-analysis for skin disease, first of all, one of the most important elements that were looked at that was looked at was the Psoriasis Area and Severity Index (PASI) response. And this is a validated standard outcome measure looking at how much a patient's psoriatic skin disease improves. And often, in recent years with more advanced therapies, we look at 3 high hurdle endpoints, PASI90, meaning a 90% improvement in skin disease. So, for PASI90, the treatments were ranked in terms of how they performed versus placebo and ended up ranking. The TREMFYA rank happens to rank the first and second amongst the 23 different regimens and 15 different treatments that were that were evaluated for joint disease signs and symptoms.
One of the major outcome measures was the ACR response rate, specifically, including ACR20 (20%, better), ACR50 (50%, better), and ACR70 (70% better) across a variety of aspects of joint disease. That includes the number of swollen joints, the number of tender joints, how a patient ranks their overall joint disease, physical function, and some other aspects, including blood tests that measure joint inflammation. In that ranking, TREMFYA ranked compatibly across advanced targeted therapies, which is really important for patients because how they feel and function with respect to their joint diseases is hugely important for their for their day-to-day activities and quality of life. The third bit was looking at this concept of structural joint damage, and that's measured using joint X-rays. And those joint X-rays are scored using a standard instrument called the Sharp/van der Heijde score (SHS). And for many years now, that's been the established regulatory instrument used to measure joint damages as captured by X-ray. And it's also used with health technology bodies payers and by guidelines committees. And again, in this NMA, TREMFYA performs comparatively to other advanced so called disease-modifying targeted therapies and scored higher in the ranking than those 2 more recent entrants, risankizumab and upadacitinib. So, all in all, when you put that together with safety analysis, that was also done here looking at serious adverse events, this confirmed TREMFYA’s well-established long-term safety profile. It was the first entrance into the interleukin 23 space and so as such, there are 5 years of safety and efficacy data available in psoriasis and 2 years or more in psoriatic arthritis. The safety profile was also confirmed and comparable to other treatments. So overall, this was consistent with TREMFYA as a very useful treatment for patients struggling with this complex disease.
RN: Were you surprised by the results of the study?
TR: We were pleased with the results of the study and unsurprised and in many ways. TREMFYA has been developed for skin psoriasis and for psoriatic arthritis over a period of a number of years. So, it's been known for some time how it how it performs generally. It's just nice to see that performance put together in a very systematic way that compares the results of different randomized trials involving different treatments to one another.
RN: What is the clinical significance of these results?
TR: One of the really valuable things that NMAs bring to the table for people who are making decisions about treatment of psoriatic arthritis is it allows you to compare across different treatments. Looking at things that matter. And the things that matter here, as we discussed, are skin inflammation, joint inflammation, progressive radiographic joint damage, and safety. And think the results of this meta-analysis will be very useful for people evaluating different treatment options for themselves or for doctors for their patients who are struggling with psoriatic arthritis. It gives them a rigorous way to make these often difficult comparisons across complex clinical trial data sets that come from multiple different clinical trials at different points in time.
RN: Were there any strengths or limitations of the study that you'd like to highlight?
TR: I think one of the strengths I would highlight is that this is the most comprehensive Network Meta-Analysis conducted today in psoriatic arthritis. Again, the number of we've updated from a comprehensive effort that was published last year to now include the most current information from TREMFYA, and to newer entrants to the to the field. So, one of the strengths is really the comprehensiveness of the effort with 15 different treatments evaluated.
The limitation I would always highlight with the Network Meta-Analysis is that it's not a substitute for randomized head-to-head clinical trial comparing different treatments. But of course, it's impractical in our in the field of medicine to conduct randomized head-to-head clinical trials of all possible treatments for any given disease. So therefore, we often lean on Network Meta-Analyses, when conducting assessments of many different treatments at the same time. Bodies who often do that include not only prescribers, but health technology bodies payers and other important stakeholders. So I think I'd highlight the strength being its comprehensiveness and the inherent limitations of any Network Meta-Analysis. Of course it's not quite a randomized controlled clinical trial, but it is the most rigorous alternatives available.
RN: Is there anything else you'd like rheumatologists now before we wrap up?
TR: I will highlight that TREMFYA, first in class interleukin 23 inhibitor, guselkumab, remains really active in the research and development space for psoriatic arthritis. We have 2 large ongoing phase 3 clinical trials enrolling at the moment. One is called SOLSTICE. SOLSTICE is evaluating TREMFYA profile in those more difficult to treat patients who have already tried and failed 1 advanced therapy like a TNF inhibitor. We've generated data in the past in that space and SOLSTICE will look to really cement the picture we have of TREMFYA’s benefits and risks for patients like that. So that's actively enrolling, and we're excited to be off to the races there.
The second one I'd highlight is a large phase 3 clinical trial called APEX. And if you remember, earlier on we discussed the various different elements of disease for a patient with psoriatic arthritis and one of them was joint damage. APEX seeks to build on data we had already generated around TREMFYA for the treatment of progressive radiographic joint damage.
So we're really looking forward to those 2 important trials to build on the comprehensive data set that have already been generated for TREMFYA. As I mentioned, 5 years of data on skin psoriasis and 2 or more years of data in psoriatic arthritis. I suppose that the last point I would leave you with is we're continuing to really develop our understanding of this molecule for patients with PsA in a rigorous way. I really look forward to sharing the results of those studies in due course.