Rheumatology Drugs Flashcards
What is Cosentyx®?
secukinumab
What is the MOA of secukinumab?
Cosentyx (secukinumab) is a human IgG1 monoclonal antibody that selectively binds to the interleukin-17A (IL-17A) cytokine and inhibits its interaction with the IL-17 receptor. IL-17A is a naturally occurring cytokine that is involved in normal inflammatory and immune responses.
What is Taltz®?
ixekizumab
What is the target of dapirolizumab pegol?
What is the major study recently published about this medication?
Anti-CD40
Phase 3 PHOENYCS GO study (published 2024) - a 48 week study of SLE pts with moderate to severe disease who were on standard of care therapy who received either dapirolizumab or placebo - those receiving dapirolizumab had significant improvement in the BILAG scores at week 38.
Aside from rituximab, what is another anti-CD20 agent? In what trial was this recently used in SLE patients?
Obinutuzumab (Gazyava).
REGENCY Phase 3 trial enrolling patients with biopsy-proven lupus nephritis (class III or class IV proliferative disease with or without membranous disease) - all patients were taking a background of mycophenolate and prednisolone and they were either given obinutuzumab for 76 weeks. By the primary and secondary end-points, obinutuzumab was superior to placebo in addition to standard of care.
What is Bimekizumab? How does it work?
Binekizumab (Bimzelex) is a humanised anti-IL-17A and anti-IL-17F monoclonal antibody that is used to treat plaque psoriasis, psoriatic arthritis, axial spondyloarthritis and ankylosing spondylitis.
Bimekizumab was FDA-approved in Oct 2023 for active moderate to severe plaque psoriasis not responding to or needing more than conventional therapy. Its uptake in Dermatology has been very strong. We have only recently (Sept ‘24) got approval for in the rheumatology world for bimekizumab for active psoriatic arthritis, active ankylosing spondylitis and active non-radiographic axial spondyloarthropathy.
The dosing in rheumatology is different to that used for active psoriasis patients - in rheumatology, we use 160mg subcut injection every 4 weeks (there is a pre-filled syringe and autoinjector). The approval is based on two big trials in psoriatic arthritis - the BE OPTIMAL and the BE COMPLETE trial, and 2 other big trials in the spondyloarthropathies (the MOBILE 1 and MOBILE 2 trials). The other takeaway from these trials is that the drug works equally well in those who are biologic naive and those who are biologic experienced.
Why is it important to treat RA early? What poor outcomes may occur if there is a delay in initiation of RA treatment?
1) More radiographic progression
2) Reduced likelihood of csDMARD free remission
Several studies have shown that a delay in treatment initiation (including first assessment by a rheumatologist delay in starting DMARDs), resulting in prolonged symptom duration, is associated with poorer outcomes:
In a meta-analysis of 12 studies in patients with RA and symptom duration of <2 years, an average 9-month delay in starting DMARDs significantly increased subsequent radiographic progression (Finckh et al, 2006)
In an early arthritis cohort, the first assessment by a rheumatologist of patients with symptom duration of ≥12 weeks was associated with a 1.3-times higher rate of joint destruction over 6 years and a hazard ratio of 1.87 (CI95% 1.17–3.00) for not achieving DMARD-free remission, as compared with assessment in <12 weeks after symptom onset. Nevertheless, assessment by a rheumatologist is delayed by about 18 weeks in patients with RA or spondyloarthritis, and only 31% of RA patients are assessed within 12 weeks of symptom onset (van der Linden et al, 2010).
On top of that, in two early arthritis cohorts it was shown that a symptom duration of less than 6 weeks was associated with a higher chance of achieving sustained DMARD-free remission than a symptom duration of 7–12 weeks, and symptom duration of more than 12 weeks. A symptom duration of less than 6 weeks did not result in less radiographic progression compared to 7-12 weeks, but was associated with less radiographic progression compared to a symptom duration >12 weeks (Niemantsverdriet et al, 2020).
A meta-analysis of 18 cohort studies and randomized controlled trials (RCTs) has confirmed that prolonged symptom duration is associated with radiographic progression and a lower chance of DMARD-free sustained remission (van Nies et al, 2014).
Clinical and radiographic outcomes were significantly better in RA-patients who started any DMARDs in the first 3 months after disease onset (compared with those who started therapy after a median of 12 months (Nell et al, 2004):
The improvement of DAS28 score was significantly higher and remission was achieved in 50% in the very early group compared with only 15% in the early group.
ACR 50% response was achieved in 60% in the very early treated patients after 36 months vs 25% in the late treated patients.
DMARD switching due to lack of efficacy were three-fold (p<0.05) more frequent among patients with a longer disease duration than in the very early RA patients. This suggests that in very early arthritis, but not in arthritis lasting for just a short time longer, a large fraction of patients respond very well to traditional DMARDs (methotrexate, sulfasalazine, leflunomide, cyclosporin A and chloroquine in this study) and disease progression can be halted rapidly.
What proportion of patients with early RA may achieve DMARD-free sustained remission?
Several studies have reported that disease-modifying antirheumatic drug (DMARD)-free sustained remission can be achieved in approximately 10%–20% of patients with early RA (Verstappen et al, 2020).
What percentage of patients with RA have bony erosions on XR within 3 months of disease onset?
25%
What percentage of patients with recent-onset RA develop bone erosions within the first 3 years of disease onset?
70%
How early does radiographic damage in early RA present with more sensitive imaging like MRI or USS?
More sensitive imaging techniques such as magnetic resonance imaging (MRI) and musculoskeletal ultrasonography (MSUS) have confirmed evidence of damage within weeks of the onset of symptoms (McGonagle et al, 1999; Wakefield et al, 2000) and their correlation with the later development of X-ray erosions
However, the role of MSUS and MRI imaging techniques in the diagnosis of early arthritis, assessment of disease activity and therapy choice in clinical practice is so far unclear and will be discussed later (in section 6.3.12).
What is the current definition of ‘early RA’?
Currently, ‘early RA’ is defined as disease duration of less than 1 year, divided into “very early RA” with disease duration of <3 months and “late early RA with duration of symptoms of 3–12 months.
What is “very early RA”?
Disease duration <3 months
What is “late early RA”?
RA with duration of symptoms 3-12 months
