With the development of conventional, biologic, and targeted disease-modifying antirheumatic drugs, the prognosis for rheumatoid arthritis has improved significantly since the 1990s. However, many patients still do not respond to available treatments [1,2]. In an interview, Prof. Andrea Rubbert-Roth, MD, explains the opportunities offered by new therapy options and what the focus is on for patients.
Prof. Dr. med. Andrea Rubbert-Roth
Cantonal Hospital St. Gallen
1. which aspects of therapy management are in focus for patients with rheumatoid arthritis (RA) today?
In RA, we have made significant advances in therapy over the last 20 years. On the one hand, this applies to the selection of available drugs, especially when a patient does not respond adequately to a conventional disease-modifying antirheumatic drug (csDMARD; usually methotrexate (MTX). On the other hand, we can now diagnose the disease earlier and ensure that as little time as possible elapses between the onset of symptoms and the presentation to the rheumatologist.
In addition, the focus is on the implementation of the treat-to-target principle. This means that together with the patient we agree on a treatment goal, such as achieving remission, and monitor the disease and therapy regularly to achieve this goal. Overall, then, the management of RA has changed significantly over the last few years, even beyond the selection of available drugs, and has become much more systematic.
2) How realistic is the therapeutic goal “remission” for RA patients in Switzerland?
First, it is important to define exactly what is meant by remission in the first place. When defined according to DAS28 (Disease Activity Score 28), individual joints may well still be swollen, although the criterion of DAS28 remission <2.6 is formally fulfilled. Patients, on the other hand, tend to understand remission as what we also define as Boolean remission – a state as if one had no RA with at most one affected joint. This naturally raises the bar considerably.
In Switzerland, we are in the privileged position that patients have rapid access to biologics or Janus kinase (JAK) inhibitors when they are not adequately controlled with MTX/csDMARD alone. Based on data from the Swiss Clinical Quality Management (SCQM) registry, it is clear that the proportion of patients with DAS28 remission has increased significantly over the last years. However, a patient diagnosed with RA today wants to be completely relieved of his or her symptoms.
3. What has been your experience in treating your patients with upadacitinib?
The Swissmedic approval of upadacitinib at the beginning of 2020 and the subsequent approval by the health insurance funds in April 2020 have made it possible to use this treatment in RA without major hurdles [3-5].
Having led the Phase III clinical trial program in Germany, I have had many years of experience with upadacitinib. I well remember a patient with highly active RA who was enrolled in a clinical trial and about whom I would have been quite concerned if she had been assigned to the placebo arm. A week after the start of treatment, she was beaming all over. So we were able to observe a good response after a short period of time, although of course we did not know formally whether the patient was receiving upadacitinib. This moment has remained very much in my memory.
4. How satisfied are you and your patients with upadacitinib treatment in terms of efficacy, tolerability, and therapy management?
We have since used upadacitinib in both clinical trials and real-word conditions. I am very satisfied with the medicine. Of course, certain questions remain unanswered, such as whether a patient who has not responded to baricitinib can benefit from switching to upadacitinib. Here we still lack data and experience.
Overall, I see upadacitinib as a very pleasant treatment for patients, which has shown good efficacy, especially in head-to-head studies.
Most patients prefer once-daily oral administration. This makes therapy with upadacitinib very simple. Often it is simple arguments that are important to patients, for example the elimination of the cold chains familiar from biologics. These often pose a major problem for patients who are particularly mobile and willing to travel. For such patients, it is very convenient to have an oral therapy option available that is also highly effective and well tolerated.
5. How important is a rapid response to therapy?
A quick response is always important. Nowadays, if a patient suffers from an active disease, a prospect of improvement in half a year is not acceptable. The patient wants to get better quickly, within a few weeks. In addition, many patients are very skeptical of corticosteroids or have certain contraindications. A quick response allows me to quickly see if a treatment is working and allows me to avoid bridging with corticosteroids in certain cases.
6. upadacitinib shows very good efficacy data both in combination with MTX and as monotherapy [6, 7]. How do you see the future of RA therapy in this regard?
It is often difficult for patients to understand why they should continue to use a drug that has failed according to all clinical criteria. Many patients do not want to take a drug such as MTX if its efficacy is not fully convincing and it may cause side effects such as feelings of fatigue, latent nausea or headache.
On the other hand, if patients tolerate MTX well, they are usually easier to convince that the results of any RA treatment are always somewhat better when combined with MTX. With biologics, this often manifests itself in a reduced incidence of anti-drug antibodies. Therefore, if MTX is well tolerated, I advise patients to continue MTX treatment when starting a new therapy, e.g., upadacitinib. When remission is achieved, discontinuation of MTX may be considered. Ultimately, patients often make such decisions themselves. This is perfectly fine, as long as the patients are doing well in the process.
Thus, overall, both combination therapy of upadacitinib and MTX and monotherapy with upadacitinib have merit. In this context, a head-to-head comparative study between MTX monotherapy, upadacitinib monotherapy, and upadacitinib-MTX combination therapy would be desirable. However, the existing data already show very impressively that upadacitinib will certainly have a high value in monotherapy.
7. How do you estimate the burden of polypharmacy for patients?
Polypharmacy means that patients require many different tablets with different dosing regimens. This quickly makes the therapy confusing and complicated, which in turn can impair the success of the therapy. Therefore, in terms of patient convenience and adherence, the simpler the therapy, the better.
8. is real-world data collected that can complete the picture? How does that help you and your patients?
I consider real-world data to be very important. After all, not all patients enrolled in sometimes complicated Phase III trials today necessarily correspond to patients in daily life. Study participants often suffer from severe RA but are otherwise healthy. Real-world patients often have a history of concomitant diseases or tumors. This results in a fundamentally different situation.
In the registration studies, a drug proves its efficacy and safety. But to capture how the drug holds up in everyday life, we need real-world data. These can be obtained from registries, such as the SCQM registry, but also from phase IV studies, in which certain questions are investigated non-interventionally that were not answered in phase III studies.
The global, ongoing, prospective, observational UPHOLD study, which also involves five Swiss centers, aims to assess treatment patterns, achievement of treatment goals, and maintenance of response over up to 24 months in approximately 1,660 patients prescribed upadacitinib [8].
9) How do you assess the importance of digital communication channels for medical information exchange, especially in relation to inflammatory rheumatologic diseases?
With regard to patient communication, digital information channels will become increasingly important, especially for younger and middle-aged patients. Nevertheless, analog information material and the conversation with the doctor or nurse remain important. Overall, this results in many different ways to inform patients about their disease and therapies – and the better informed the patient, the greater the therapeutic success.
With regard to the exchange of information between physicians of different specialties, I consider online platforms to be useful, where relevant information can be accessed quickly, for example on the interaction potential or side effects of drugs, but also on their potential overlapping use in different inflammatory diseases.
In any case, it is important that digital information media are presented in an appealing way and enable users to quickly find an answer to their question.
Literature
Brief technical information RINVOQ®
This text was produced with the financial support of AbbVie AG, Alte Steinhauserstrasse 14, 6330 Cham.
CH-RNQR-220013_02/2022
Contribution online since 09.03.2021
Post updated 11.02.2022
