There has been substantial progress over the last decade in understanding the origins and inflammatory progressions of psoriatic arthritis (PsA), which has led to the development of improved pharmacologic agents. While there are now a wide variety of biologics, biosimilars, and targeted treatments available, several novel agents are currently in late-stage trials and have the potential to dramatically improve care. “Comprehending the PsA Agents in Late-Stage Clinical Development” will review relevant clinical trial data and explore all the potential uses of novel investigational therapies for PsA.
Comprehending the PsA Agents in Late-Stage Clinical Development
Comprehending the PsA Agents in Late-Stage Clinical Development
Welcome to CME on ReachMD. This activity, entitled “Comprehending the PsA Agents in Late-Stage Clinical Development” is provided by National Psoriasis Foundation with educational partner Rockpointe and is supported by an independent educational grant from Lily.
Prior to beginning the activity, please be sure to review the faculty and commercial support disclosure statements as well as the Learning Objectives at ReachMD.com.
Over the last decade, we’ve seen significant progress in understanding the origins and inflammatory progressions of psoriatic arthritis, which has led to the development of improved targeted therapies. On today’s program, we’ll be exploring some of these newer therapeutic agents in development for psoriatic arthritis as well as their respective benefits and limitations. This is CME on ReachMD and I’m Dr. Matt Birnholz. Joining me to discuss the promising psoriatic arthritis agents in late-stage development is Dr. Marina Magrey. Dr. Magrey, welcome to the program.
Thank you for having me.
So, to start, Dr. Magrey, let’s take some time to talk about the treatments that are currently being investigated in clinical trials, and let’s start with bimekizumab. What can you tell us about this potential option?
Bimekizumab is an IL-17 blocker, so how it differs from other IL-17 cytokine blockers is that it’s a dual inhibitor of IL-17A and IL-17F cytokine. The safety and efficacy was looked in the phase 2 trial, an 8-week proof of concept study of 52 patients with psoriatic arthritis, and during this phase 2 trial, it demonstrated efficacy on disease activity not only in the joints, but also in the skin, it was safe and well tolerated.
And Dr. Magrey, what about the IL-23 blockers, which are also in the pipeline? What can you tell us about that drug class?
IL-23 blocker, ustekinumab, has already been approved and available for treatment of psoriatic arthritis, but there are some other, IL-23 blockers which are still in pipeline and one of them is guselkumab, and guselkumab it’s a B19 subunit blocker, a receptor blocker, and its safety and efficacy was tested in phase 3 psoriatic arthritis trial, called VOYAGE 1 and VOYAGE 2 and the data was recently just presented in the American College of Rheumatology. In this study, there were about 1,829 study patients and at 24 weeks, patient achieved IgA scores of 1 and 0 in the guselkumab group compared to adalimumab group. Adalimumab is a TNF blocker, which is already approved for the treatment of psoriatic arthritis, so it looks like a very good option for the treatment of psoriatic arthritis, and it’s already been approved for the treatment of psoriasis. Risankizumab is another IL-23, p19 blocker, which is also being studied for the treatment of psoriatic arthritis and has been shown to maintain improvement in both joint and skin symptoms in 24 weeks, and also been shown to decrease radiographic progression of the disease. Completion of phase three trials will be in 2024. Risankizumab is available for treatment of psoriasis too and as the currently phase 3 studies are going on for the treatment of psoriatic arthritis, and in phase 2 studies, it has actually shown, sustained improvement in both joint and skin symptoms and also slowed down radiographic progression. So, the phase 3 studies are currently under way and we’re hopeful that in a year or so, it’ll be hitting the market for the treatment of psoriatic arthritis. Tildrakizumab is another IL-23 blocker and has been tested, in another study in 355 patients. The data was presented in a conference – European Union League Against Rheumatology and has also been shown to be efficacious in psoriatic arthritis.
Thank you, Dr. Magrey, that was an excellent rundown of the IL-23 blockers and the current investigations they’re in. I want to spend a moment also talking about rodalumab, which, as I understand it, had phase 3 psoriatic arthritis trials that were recently suspended. What can you tell us about that?
Brodalumab is another IL-17 receptor blocker and was tested in patients with active psoriatic arthritis who had no prior treatment with IL-17 blockers but were previously treated with IL-23 blocker therapy or TNF inhibitors, and two doses of brodalumab were tested in this study and, at week 12, it showed significant improvement both in ACR 20 and ACR 50 response compared to placebo, regardless if the patients were biologic naïve or had been exposed to biologic therapy. However, the phase 3 studies of the drug had to be suspended because of the potential concerns of depression and suicidal ideation in these patients. So, these studies were suspended and FDA has put a label warning on it that it can cause suicidal ideation.
For those just joining us, this is CME on ReachMD. I’m Dr. Matt Birnholz, and I’m speaking with Dr. Marina Magrey about promising psoriatic arthritis agents in late stage trials. So, Dr. Magrey, we spoke earlier about both the IL-17 inhibitors and the IL-23 inhibitors that you helped focus on and gave us better clarity around, but I want to shift over now to another drug class that rheumatologists should definitely be aware of. What can you tell us about the role of JAK inhibitors and what role they could play potentially in the management of psoriatic arthritis?
Effective therapies for treating psoriatic arthritis have emerged over the last 15 years and newer agents are continuing to be discovered, allowing for better therapeutic options for controlling the arthritis and preventing joint damage. Another class of agent that has been found to be efficacious in the treatment of psoriatic arthritis is janus kinase inhibitors. Currently, we have one janus kinase inhibitor that has been approved for the treatment of psoriatic arthritis, which is tofacitinib, but there are other janus kinase inhibitors for the management of psoriatic arthritis, and one of them is upadacitinib. Currently in two phase 3 trials in patients with active psoriatic arthritis that had inadequate response to at least one biologic DMARD, upadacitinib has been used and tested against a placebo and also against a TNF inhibitor, adalimumab. And the study will be completed in two years.
So, Dr. Magrey, given everything we’ve spoken about here, let’s shift gears and consider the patient resources that we should be sharing. What resources are out there that patients should be aware of?
There are multiple patient advocacy groups that are available, for these patients. We have National Psoriasis Foundation Resource, and the patients can go to their website and it gives a lot of information about the disease, about the treatment options available, and we’re in an era where we can do what we call personalized treatment of these patients with so many therapies available for psoriatic arthritis. In the past, we used to be borrowing treatment from rheumatoid arthritis but now we have some medications which are exclusively for treatment of psoriatic arthritis. The site will give them information about the comorbidities, the specialists available in their areas, what is the goal of treatment, and how to be prepared for their appointment. They could go to a website called www.psoriasis.org and there’s also a phone number available – 1-800-723-9166, if the patients can call to get more information about their disease, how to control their disease, how to schedule appointments to see a specialist in psoriatic arthritis and get treatment in a timely manner.
Excellent, Dr. Magrey. Thank you. And before we close, are there any main takeaways that you want to leave with our audience today?
The, the message I want to give to the patient suffering from psoriatic arthritis today is that we are in an era of personalized treatment. What that means is that we have multiple drugs available for the treatment of psoriatic arthritis. In the past, we had borrowed this treatment from rheumatoid arthritis, but now we have drugs that are exclusively available for psoriatic arthritis. There are now therapies which affect multiple cytokines. Since psoriasis is a complex disease, we are able to tackle it at multiple levels. Newer treatments are still in pipeline and will be available in a few years for those patients who don’t respond to traditional treatment, and there are now several resources available through National Psoriasis Foundation to help in facilitate patients’ understanding and encourage shared decision making in psoriatic arthritis.
Well, it’s fantastic to know that there are new therapies as well as additional educational resources available for our psoriatic arthritis patients. I very much want to thank my guest, Dr. Marina Magrey, for sharing these resources with us. Dr. Magrey, it was great talking with you today.
And it was great speaking with you too today, Matt.
You have been listening to CME on ReachMD. This activity is provided by National Psoriasis Foundation with educational partner Rockpointe and is supported by an independent educational grant from Lily.
To receive your free CME credit, or for other episodes in this series, go to ReachMD.com/I-L-17-P-s-A. Thank you for listening.
MARINA N. MAGREY, MD
Associate Professor of Medicine
Case Western Reserve University School of Medicine
Director, Arthritis Clinic and Fellowship Program
MetroHealth Medical Center
Marina N. Magrey, MD is Associate Professor of Medicine at the Case Western Reserve University School of Medicine and the Director of the Arthritis Clinic and Fellowship Program at MetroHealth Medical Center in Cleveland, OH. She previously served as the Medical Director of the MetroHealth Beachwood Medical Center.
Dr. Magrey studied pre-medicine at the Government College for Women in India, then completed her MBBS at the University of Kashmir. She then completed an internship and residency in the Department of Medicine, as well as a fellowship in the Division of Rheumatology, at the Cleveland Clinic.
A member of the American College of Rheumatology, Cleveland Society of Rheumatology, Dr. Magrey serves on the Education Committee of the Spondyloarthritis Research and Treatment Network (SPARTAN). She is the invited member of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) and the Assessment of Spondyloarthritis International Society (ASAS).
The author or co-author of numerous journal articles, book chapters, and abstracts, Dr. Magrey is also an ad-hoc reviewer for several peer-reviewed journals, including Arthritis Care and Research, Seminars in Arthritis and Rheumatism, International Journal of Rheumatic Diseases, and the Journal of Rheumatology.
SIBA P. RAYCHAUDHURI, MD
Chief Rheumatologist, Sacramento VAMC
Professor, Department of Medicine/Rheumatology, Allergy, and Clinical Immunology
University of California-Davis
Siba P. Raychaudhuri, MD is the Chief Rheumatologist at the Sacramento VAMC and a Professor in the Department of Medicine/Rheumatology, Allergy, and Clinical Immunology at the University of California-Davis (UC-Davis) in Davis, CA. He is also the Director of the Rheumatology and Immunology Training Fellowship program at UC-Davis and teaches courses on clinical medicine, immunology, and immuno-pharmacology to medical students, immunology graduate students, and medical residents. Dr. Raychaudhuri established the Psoriasis Research Center at UC-Davis and Sacramento VAMC and has directed one of the most successful psoriasis research programs. He is also Director of the Psoriatic Disease Clinic and, at the Stanford University Medical Center, he worked on cutting-edge immune-based therapies for autoimmune diseases.
Dr. Raychaudhuri earned his MBBS from Medical College Calcutta in India and his medical doctorate from the Post Graduate Institute of Medical Education and Research in India. He completed his postdoctoral fellowship at the Stanford University School of Medicine and Psoriasis Research Institute in Palo Alto, CA. He then completed a fellowship in rheumatology at the Stanford University School of Medicine.
A former member of the Board of Directors of the Spondyloarthritis Research and Treatment Network, Dr. Raychaudhuri serves on the Editorial Boards of Clinical Reviews in Allergy and Immunology and the Indian Journal of Dermatology. He is also an ad-hoc reviewer for numerous peer-reviewed journals, including the New England Journal of Medicine, Journal of Investigative Dermatology, Journal of Autoimmunity, and British Journal of Dermatology.
The National Psoriasis Foundation (NPF) adheres to the policies and guidelines, including the Standards for Commercial Support, set forth to providers by the Accreditation Council for Continuing Medical Education (ACCME) and all other professional organizations, as applicable, stating those activities where continuing education credits are awarded must be balanced, independent, objective, and scientifically rigorous.
All persons in a position to control the content of a continuing medical education program provided by NPF are required to disclose any relevant financial relationships with any commercial interest to NPF as well as to learners. All conflicts of interest are identified and resolved by NPF in accordance with the Standards for Commercial Support in advance of delivery of the activity to learners. The content of this activity was vetted by an external reviewer to assure objectivity and that the activity is free of commercial bias.
The steering committee reported the following relevant financial relationships that they or their spouse/partner have with commercial interests:
Siba Raychaudhuri, MD: Grants/Research Support: AbbVie, Amgen, Johnson & Johnson, Lilly, Novartis, Pfizer, Sun Pharmacy; Advisory Board: Johnson & Johnson, Lilly, Novartis, Pfizer
Marina Magrey, MD: Consultant: Novartis; Advisory Board: Eli Lilly, Novartis; Clinical Trials: AbbVie, UCB Pharma
Non-faculty Content Contributors
Non-faculty content contributors and/or reviewers reported the following relevant financial relationships that they or their spouse/partner have with commercial interests:
Nicolle Rochino, PharmD, Rh; Blair St. Amand; Andi Agnew: Nothing to disclose
The contents of some CME/CE activities may contain discussions of non-approved or off-label uses of some agents mentioned. Please consult the prescribing information for full disclosure of approved uses.
This activity is intended for rheumatologists and others on the rheumatology care team, as these clinicians are the main care providers for patients with PsA.
This program is designed to address ACGME and NAM competencies, including delivering patient-centered care and practicing evidence-based medicine.
At the conclusion of this activity, participants should be able to:
- Evaluate the safety and efficacy data for PsA agents in late-stage clinical development
The National Psoriasis Foundation is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.
The National Psoriasis Foundation designates this enduring material for a maximum of 0.25 AMA PRA Category 1 Credit(s)TM. Physicians should only claim credit commensurate with the extent of their participation in the activity.
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