ABSTRACTIntroduction: Biologic therapy has revolutionized the treatment of immune mediated inflammatory diseases (IMID), such as inflammatory bowel disease (IBD), rheumatoid and psoriatic arthritis, ankylosing spondylitis and psoriasis. Nevertheless, some patients exhibit primary nonresponse (PNR) or secondary loss of response (SLR) to biologics.Areas covered: This collaborative review provides data on the role of therapeutic drug monitoring (TDM) in IMID for optimizing biologic therapy including infliximab, adalimumab, certolizumab pegol etanercept and golimumab vedolizumab, secukinumab and ustekinumab.Expert opinion: Most exposure-response relationship studies show a positive correlation between biologic drug concentrations and favorable therapeutic outcomes in IMID with higher drug concentrations typically associated with more objective outcomes. Clinically, reactive TDM rationalizes the management of PNR and SLR to anti-tumor necrosis factor therapy and is emerging as the new standard of care in IBD as it is also more cost-effective than empiric dose escalation. Preliminary data suggest that proactive TDM with the goal to achieve a threshold drug concentration is associated with better therapeutic outcomes when compared to empiric drug optimization and/or reactive TDM of infliximab and adalimumab in IBD. However, more data from well-designed prospective studies are needed to prove the benefit of TDM-based algorithms in real life clinical practice in IMID. 相似文献
The 52‐week results from the CLEAR (NCT02074982) study showed high and superior efficacy of secukinumab versus ustekinumab in clearing skin and improving patient‐reported outcomes, with comparable safety profile in subjects with moderate to severe psoriasis. Here, we analyzed the efficacy and safety of secukinumab in Asian subjects from the CLEAR study. In this double‐blind, phase IIIb study, eligible subjects with moderate to severe plaque psoriasis were randomized (1:1) to receive s.c. injection of secukinumab 300 mg or ustekinumab as per label. Of 62 subjects included in Asian subanalyses, 23 were randomized to secukinumab and 39 to ustekinumab. A significantly higher proportion of subjects achieved 90% or more improvement in Psoriasis Area and Severity Index (PASI 90) with secukinumab versus ustekinumab at week 16 (78.3% vs 35.9%, P =0.0010) and at week 52 (60.9% vs 33.3%, P =0.0196). Similarly, a higher proportion of subjects achieved PASI 100 with secukinumab versus ustekinumab at week 16 (43.5% vs 10.3%, P =0.0029) and at week 52 (30.4% vs 12.8%, P =0.0704). The median time to achieve 50% improvement in baseline PASI was 2.8 weeks in the secukinumab group versus 6.3 weeks in the ustekinumab group. The safety profile of secukinumab was in line with the known profile and no deaths occurred. Overall, 95.7% and 84.6% of subjects remained on secukinumab and ustekinumab, respectively. Similar to the core study, secukinumab showed sustained and superior efficacy with faster response versus ustekinumab, and no new or unexpected safety concerns were identified, in Asian subjects with moderate to severe plaque psoriasis. 相似文献
Introduction: Interleukin (IL)-17 is a proinflammatory cytokine considered to play a significant role in the immunopathogenesis of ankylosing spondylitis (AS)/axial spondyloarthritis (axSpA) as well as of other spondyloarthritides. There is a number of substances targeting IL-17, which are at different stages of development in the axSpA indication.
Areas covered: This review summarizes the current evidence on the role of IL-17 in the pathophysiology of axSpA and provided a comprehensive review of clinical and radiographic outcomes as well as of safety data from studies with IL-17A inhibitors secukinumab and ixekizumab. Ongoing studies on other IL-17 inhibitors (bimekizumab, brodalumab and BCD-085) that are being developed are also summarized.
Expert opinion: The development of the IL-17 inhibitors has expanded AS treatment with effective options and confirmed the pathophysiological role of IL-17 in axSpA. IL-17 inhibition showed sufficient efficacy against signs and symptoms of the disease even after the failure of tumor necrosis factor inhibitors, being at the same time reasonably safe. 相似文献
We evaluated the efficacy and safety of interleukin (IL)-17 inhibitors (IL-17i) by analyzing 66 patients with psoriasis treated with secukinumab (n = 25), ixekizumab (n = 17) and brodalumab (n = 24) at Kurume University Hospital between December 2014 and June 2019. The mean Psoriasis Area and Severity Index (PASI) scores at baseline were 12.9, 13.4 and 9.9 in the secukinumab, ixekizumab and brodalumab groups (SECg, IXEg and BROg), respectively. At the 6-month evaluation, the mean PASI scores were 1.7, 1.1 and 0.5 in SECg, IXEg and BROg, respectively. The proportion of patients achieving PASI of 3.0 or less was significantly lower in SECg. Drug survivals showed no significant difference among the groups. Although one patient in IXEg died due to an unknown cause, no serious IL-17i-associated adverse event was observed. This study showed high efficacy and relatively low risk of the treatment with IL-17i. 相似文献
There are limited data on the safety and efficacy of switching to secukinumab from cyclosporine A (CyA) in patients with psoriasis. The purpose of the present study was to assess the efficacy and safety of secukinumab for 16 weeks after direct switching from CyA in patients with moderate‐to‐severe psoriasis. In this multicenter, open‐label, phase IV study, 34 patients with moderate‐to‐severe psoriasis and inadequate response to CyA received secukinumab 300 mg s.c. at baseline and weeks 1, 2, 3, 4, 8 and 12. The primary end‐point was ≥75% improvement from baseline in Psoriasis Area and Severity Index score (PASI 75) at week 16. The efficacy of secukinumab treatment was evaluated up to week 16, and adverse events (AE) were monitored during the study. The primary end‐point of the PASI 75 response at week 16 was achieved by 82.4% (n = 28) of patients receiving secukinumab. Early improvements were observed with secukinumab, with PASI 50 response of 41.2% at week 2 and PASI 75 response of 44.1% at week 4. AE were observed in 70.6% (n = 24) of patients, and there were no serious AE or deaths reported in the entire study period. Secukinumab showed a favorable safety profile consistent with previous data with no new or unexpected safety signals. The results of the present study show that secukinumab is effective in patients with psoriasis enabling a smooth and safe direct switch from CyA to biological therapy. 相似文献
There are no studies which directly compare efficacy in Psoriasis Area and Severity Index (PASI) response of secukinumab and ixekizumab. The main aim of this study was to compare the efficacy and safety of both drugs used to treat moderate‐to‐severe psoriasis patients over 52 weeks. Secondary objectives were to identify which factors related to prior biologic treatment influenced their efficacy and analyze data obtained at 12 weeks. A retrospective observational study was carried out, in which a group of the first 59 patients treated with secukinumab after its commercialization, was compared with another group of the first 29 patients treated with ixekizumab. The PASI 75, 90, and 100 response obtained at 52 weeks was 64.4%, 49.2%, and 41.4% for secukinumab and 75.9%, 62.1%, and 41.4% for ixekizumab, respectively, with no statistically significant differences. Regarding previous biological treatment, both treatments showed a decrease in efficacy as the number of prior biologics increases. No differences were found between secukinumab and ixekizumab in bio‐naïve or bio‐experienced patients, with the exception of a higher PASI 75 response at week 52 for ixekizumab in those patients with two or more previous biologics (P = .039) Secukinumab and ixekizumab have demonstrated high efficacy and safety, with no statistically significant differences. 相似文献
The efficacy and safety of secukinumab, a fully human anti‐interleukin‐17A monoclonal antibody, has been evaluated for moderate to severe plaque psoriasis in global trials which have included a low proportion of Asian subjects. We analyzed the efficacy and safety of secukinumab in Taiwanese patients in a phase III global clinical trial (ERASURE). Fifty‐one Taiwanese patients were randomized into s.c. placebo, 150 and 300 mg secukinumab treatment groups. The proportions of patients who achieved 75% or more improvement in Psoriasis Area and Severity Index (PASI‐75) at week 12 were 87.5% with 300 mg secukinumab, 70% with 150 mg secukinumab, 0% with placebo. Of the patients receiving 300 mg secukinumab, 68.8% achieved PASI‐90 at week 12. Analysis of overall patients receiving 300 mg secukinumab for 12 weeks showed that the proportion of PASI‐75 responders was less in patients with body mass index of 25 or more than less than 25. During the entire 52 weeks, the incidence of adverse events (AE) was consistent with the overall population in ERASURE. The most common AE (cases/per 100 patient‐year) during the entire treatment period were upper respiratory tract infection and pruritus. The duration of upper respiratory tract infection per 100 patient‐year was approximately 399 days in placebo, 1261 days in 150 mg secukinumab and 1805 days in 300 mg secukinumab. The safety and efficacy of secukinumab in Taiwanese patients was compatible with the global phase III study in the treatment of moderate to severe plaque psoriasis. 相似文献
ABSTRACTBackground: Real-life data often highlight the side effects of certain drugs not previously reported in randomized controlled trials (RCTs).Objective: To describe cutaneous inflammatory eruptions in psoriatic patients treated with an anti IL-17A agent (secukinumab or ixekizumab).Methods: Retrospective analysis of a cohort of patients with chronic plaque psoriasis who started an anti IL-17A agent between September 2016-February 2019 and who developed cutaneous inflammatory eruptions during treatment. A systematic review of similar events reported in the literature was performed.Results: Data of 468 patients were reviewed and 27 cutaneous inflammatory eruptions of 27 (5.8%) patients were collected. The eruptions appeared after a mean of 16.9 ± 17.0 weeks of therapy showing a classical acute eczema in 11 patients (40.7%), an atopic dermatitis-like rash in 11 patients (40.7%) and a psoriasiform eruption in 5 patients (18.5%). Histopathology of 12/27 cases showed epidermal spongiosis in all these variants.Conclusion: We described the clinic-pathologic features of some eczematous eruptions occurring in psoriatic patients, 3–4 months after treatment initiation with an anti IL-17A agent. Further investigations are needed to explain this phenomenon, that might be defined a paradoxical adverse event, based upon the role of IL17 in eczema pathogenesis. 相似文献