Articles By Md Yuzaiful Md Yusof, MRCP(UK), PhD
Update on Sjogren's disease trials
With better endpoint and patient selection strategy over the last 4 years, many new therapies have met their endpoints/shown promising signal in the Phase 2 randomised controlled trials in Sjogren's disease (iscalimab, ianalumab, dazodalibep, and sequential therapy belimumab + rituximab). Since many previous studies have shown the discordance between physician assessment and patient’s symptom burden, there is a glimmer of hope with the efficacy signals demonstrated by both iscalimab and dazodalibep in two patient cohorts; a) cohort 1 = high disease activity with variable symptom burden and b) cohort 2 = high symptom burden but low disease activity. EULAR 2024 offered additional updates.
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Update on low-dose glucocorticoids in SLE
Glucocorticoids (GC) have been the mainstay of treatment in SLE for nearly three quarters of a century. GC induce a range of anti-inflammatory effects, quickly relieve some symptoms and lower mortality in some life-threatening flares. However, they also have multiple side effects that limit the duration of treatment, as well as the dose used. Accordingly, the 2023 EULAR recommendations for SLE set a target dose of ≤5mg/day. Is low dose GC an achievable target?
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Impact of regulatory warning on JAK inhibitors
The development of JAK inhibitors represents an advance for the treatment of inflammatory rheumatic diseases. However, the enthusiasm in using this target has waned since the publication of the ORAL surveillance clinical trial in 2022. Subsequently, both the FDA and EMA issued a warning on using JAKi in patients with certain risk factors, e.g., ≥65 years, at increased risk of MACE, current smoker or past smoker and at increased risk of cancer, should other alternative treatment be available. So, how has this warning impacted on JAKi development and use?
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SLE Preview: abolishing refractory with CAR-T and better B-cell therapies
Inhibition of B cell activating factor (BAFF) and B cell depletion are the two most evaluated strategies over the last 15 years in the field of SLE therapeutics, with licensing of belimumab and off-label use of rituximab.
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ICYMI: Glucocorticoids-free zone in SLE?
For over 70 years, glucocorticoids, (GC) have been a part of standard therapy in SLE. They are classically used to not only induce remission or treat an acute flare, but also as maintenance therapy. They are a valuable 'friend' if used wisely, and can become a 'foe' if used excessively.
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Next generation JAK-inhibition strategies
It has been just over a decade since the approval of tofacitinib (JAK1/JAK3-inhibitor) by the US FDA for the treatment of rheumatoid arthritis. Since then, baricitinib (JAK1/JAK2-i), filgotinib and upadacitinib (both selectively targeting JAK1) also have been licensed for the treatment of rheumatoid arthritis. As there are many more JAK-inhibitors evaluated in clinical trials currently, how do you stand out?
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Early aggressive treatment in SLE: are we there yet?
Early treatment with DMARDs has revolutionised the outcomes of patients with rheumatic arthritis. However, this concept has not been fully extrapolated to other autoimmune rheumatic diseases such as systemic lupus erythematosus.
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The impact of SGLT2-inhibitor on SLE outcomes
Since chronic kidney disease is one of the strongest CV risk factors, any new strategy to reduce proteinuria and avoid a decline in renal function may likely improve patient outcomes. In large cardiovascular outcome trials, the use of a fairly new-kid-on-the-block therapy, sodium–glucose cotransporter-2 inhibitors (SGLT2i) appear to be both cardio and renal-protective. Would the use of SGLT2i have the same impact in SLE?
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Glucocorticoids-free zone in SLE?
For over 70 years, glucocorticoids, (GC) have been a part of standard therapy in SLE. They are classically used to not only induce remission or treat an acute flare, but also as maintenance therapy. They are a valuable 'friend' if used wisely, and can become a 'foe' if used excessively.
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A step change towards self-empowerment for people living with SLE
In my focus group consisting of people living with SLE and their carers, one of the keys issues raised by them was pertaining to poor reliable information about their condition. At the 2023 EULAR Congress in Milan, I learned about the wide scale dissemination and international launch of Lupus100.org project.
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