Key insights from EULAR 2023
The Galapagos symposium at EULAR 2023 featured presentations from Professor Ennio Giulio Favalli (Chair), Professor Anja Strangfeld, and Dr James Galloway, and sought to review the key considerations when selecting a treatment for patients with Rheumatoid Arthritis (RA).
Specifically, it set out to explore the efficacy and safety of JAK inhibitors in RA, including filgotinib clinical trial and real-world data, and to discuss the practical use of JAK inhibitors in the context of recent developments in the RA treatment landscape.
Professor Favalli started his presentation by emphasising the importance of early inflammation control in RA management due to its links with chronic pain, fatigue, disability, depression, anxiety, and an increased risk of comorbidities, leading to higher mortality,1–7 and endorsed EULAR's treat-to-target strategy, aiming for sustained remission or low disease activity.8 This approach may necessitate multiple, successive therapies with diverse modes of action throughout a patient’s life.8
Treatment selection should be a shared decision with the patient, and consider many factors:
Treatment selection should be collaborative, factoring in patient-related aspects such as age, sex, comorbidities, lifestyle, and treatment goals, alongside treatment-related elements like efficacy, safety, and drug interactions. Disease-specific factors also play a role.9–13 Professor Favalli stressed the necessity of regular reassessments of the benefit-risk ratio in line with evolving patient conditions and scientific evidence. He illustrated this approach via three scenarios demonstrating that each patient has their own RA management journey.
Filgotinib’s role in reducing pain, a priority for RA patients:
Professor Favalli first introduced the case of Ben, a 44-year-old RA patient exhibiting high disease activity, early erosions, methotrexate unresponsiveness, and needle phobia. Adhering to EULAR guidelines, Favalli suggested synthetic or biological drugs, including JAK inhibitors, for such cases.8
Pain, a crucial issue for RA patients (less than 30% report satisfaction with their pain level) was highlighted, with Favalli noting JAK inhibitors' significant pain management capabilities.14,15 He pointed out baricitinib's superior effectiveness vs. adalimumab against non-inflammatory pain as revealed in the RA-BEAM trial,16 and noted that this was likely due to JAK inhibitors penetrating the blood-brain barrier.17,18
Furthermore, the FINCH 1 trial showed filgotinib-treated patients reported greater pain relief than adalimumab patients, underscoring filgotinib's potential for enhanced pain control.19
Appropriateness of filgotinib for patients unresponsive to a first biologic DMARD:
Next, Professor Favalli presented the case of Lydia, a 60-year-old RA patient with comorbid osteoporosis, still displaying high disease activity despite combination therapy. EULAR recommends such patients switch from the first TNF inhibitor to a different targeted drug.8
He noted that FINCH 2 trial data showed consistent ACR70 responses with filgotinib, regardless of the patient's previous treatment history, indicating its potential for various unresponsive cases.20 Long-term findings from the FINCH 4 trial further confirmed the sustained effectiveness of filgotinib, highlighting its efficacy in maintaining remission and managing refractory RA patients like Lydia.21 This suggests filgotinib's potential for a wide range of patients unresponsive to different treatments.
Filgotinib as an option for patients requiring monotherapy:
Finally, Professor Favalli the case of Jennifer, a 56-year-old woman with RA, suffering from moderate disease activity and intolerance to methotrexate. EULAR recommends IL-6 or JAK inhibitors for such patients requiring monotherapy.8
He shared Phase II DARWIN trial results showing superior ACR20 response with filgotinib monotherapy over placebo.22 Long-term results from the DARWIN 3 extension indicated a stable response even with filgotinib monotherapy,23 and safety data revealed expected and not excessive adverse events.24
Clinical data demonstrate real world effectiveness of filgotinib:
Professor Strangfeld shared data from a German study on filgotinib prescription in 300 RA patients. The main drivers were its oral administration and rapid action, with 80% showing reduced disease activity in six months, and a third achieving remission.25
These outcomes were echoed in the FILOSOPHY study, where many achieved low disease activity (CDAI <10) within a month, and early improvements in pain and fatigue.26 Filgotinib's efficacy was also validated in real-world settings, as confirmed by the Italian GISEA registry.27
No unexpected safety signals for filgotinib in real-world settings:
Professor Strangfeld moved to a discussion of JAK inhibitors' safety in RA patients, using the case of Angela, a 68-year-old patient with high disease activity despite biological treatment.
She emphasized the EULAR recommendations to switch to another biological DMARD or a JAK inhibitor after a failure with a biological DMARD,8 and noted that this shed light on a warning from the ORAL Surveillance study which indicated increased cardiovascular events and a minor rise in malignancies with tofacitinib.28–31
However, she noted real-world data varies due to patient profiles, healthcare environments, and physician practices.32,33 Despite these variables, no alarming safety signals for JAK inhibitors in RA patients have surfaced. Specifically, filgotinib users demonstrated improved clinical and patient-reported outcomes without unexpected safety signals in real-world scenarios.34–40
Dr. Galloway returned to the theme of individualising treatment strategies based on the four specific patient scenarios presented by his peers, noting that JAK inhibitors, including filgotinib, may be a suitable treatment option for eligible patients with RA.
He highlighted the EULAR guidelines which stress sustained remission or LDA as the target for all RA patients, and emphasised that when poor prognostic factors are present following the initial csDMARD, a bDMARD should be added. However, he noted, it is also possible to consider JAK inhibitors, with the caveat that individual patient risk factors need to be taken into account.8
In patients with RA, age may have a greater influence on safety outcomes vs. other traditional CV risk factors.
Dr. Galloway illuminated risk factors using filgotinib clinical trial data, showing an increase in major adverse cardiovascular events (MACE) with age: roughly 0.23 in under-65 patients, versus 0.97 in over-65s.41 Additionally, he underscored the potent influence of age and other cardiovascular elements on the likelihood of adverse occurrences, such as malignancies, infections, and venous thromboembolisms (VTE). He concluded that age plays a dominant role in risk.41
Efficacy for filgotinib even at lower doses:
Discussing possible risk mitigation, Dr. Galloway proposed that lowering medication dosage could potentially decrease event rates. Notably, he mentioned that such a strategy wouldn't necessarily compromise efficacy.
He evidenced this with Finch 4 data, which showed that more patients aged 65 or above achieved DAS28-CRP remission with a 100 mg filgotinib dose, compared to a 200 mg dose, and this effect was sustained through to 156 weeks.41
The panel discussion began with a practical point around whether the data on risk of MACE, VTE or malignancy should modify screening strategies in candidates for JAK inhibitors.
Dr. Galloway reiterated the need for continuous cardiovascular risk screening and holistic patient management in practice. The consensus was that while screening tests are crucial, their application should be proportionate to potential risks, negating the need for mandatory echocardiography before prescribing JAK inhibitors.
Use of corticosteroids:
A final point of discussion touched on the use of corticosteroids. It was noted that, despite advancements in treatments, many patients still receive small doses of corticosteroids, raising concerns due to the associated long-term adverse effects. The persistent use of these drugs is influenced by their decades-long usage and a general unawareness of their adverse event profile.
However, the panel agreed that adopting steroid-sparing strategies, demonstrated successful in diseases like vasculitis, is imperative for rheumatoid arthritis patients.
In conclusion, the symposium highlighted three key take outs.
Watch the symposium recording on demand in full