A Review of Ustekinumab in the Treatment of Psoriatic Arthritis

Roberts, Janet; O’Rielly, Darren D.; Rahman, Proton

doi:10.2217/imt-2017-0149

Cited by 19 publications

(14 citation statements)

References 57 publications

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“…87,88 It is currently under evaluation in SLE since a decrease in disease activity was observed in animal models lacking the shared IL-12/23 p40 subunit, suggesting this could be a potential target also in humans. 54 Phase III and other clinical trials confirmed the efficacy of this novel mAb in treating moderate to severe plaque psoriasis, [89][90][91] where ustekinumab was even superior to anti-TNFa agents. A meta-analysis showed that the likelihood expressed as risk ratio (RR) for achieving psoriasis area and severity index improvement by 75% (PASI75) at week 12 was 18.28 (95% CI 12.76-26.17 p < 0.001) for ustekinumab 45 mg compared to placebo and 20.21 (95% CI 13.85-29.49 p < 0.001) for ustekinumab 90 mg compared to placebo.…”

Section: Il-17 In Slementioning

confidence: 92%

“…74,87 By linking this subunit, it precludes the binding to IL-12Rb1 cell surface receptor, thereby hindering the activity of both cytokines. 88 Ustekinumab has been recently approved by the U.S. Food and Drug Administration and the European Medicines Agency for different autoimmune diseases, including psoriasis, psoriatic arthritis, 89 and Chron's disease. 87,88 It is currently under evaluation in SLE since a decrease in disease activity was observed in animal models lacking the shared IL-12/23 p40 subunit, suggesting this could be a potential target also in humans.…”

Section: Il-17 In Slementioning

confidence: 99%

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IL-12 and IL-23/Th17 axis in systemic lupus erythematosus

Larosa

Zen

Gatto

et al. 2019

Exp Biol Med (Maywood)

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Systemic lupus erythematosus (SLE) is a very complex disease where multiple immunological pathways can concur in inducing tissue damage. Cytokines are key mediators in this process and among them the role of interleukin (IL)-12 and the IL-23/Th17 axis has recently emerged. IL-12 and IL-23 have a heterodimeric structure with a common subunit, named p40. Although they share a partially common structure, their functions appear slightly different. Indeed, IL-12 is a key cytokine in inducing an efficient T helper 1 (Th1) response and in Th differentiation, while IL-23 plays a crucial role in chronic inflammation and Th17 cell activation, which results in IL-17 secretion. The increasing knowledge on the interaction between IL-12 and IL-23/Th17 axis in the development of autoimmune diseases has led to the identification of new therapeutic strategies targeting these immunological pathways. IL-23/Th17 axis has recently been suggested to be essential in developing lupus nephritis, both in mice and in humans. In keeping with these observations, ustekinumab, a fully human IgG1κ monoclonal antibody (mAb) directed towards p40 subunit, has been investigated in SLE. Promising data from a phase II randomized controlled trial in SLE patients suggest that this mAb might be a potential novel therapeutic strategy in SLE. In this review, we summarize the complex interaction between IL-12 and IL-23/Th17 axis in SLE with a special focus on drugs which affect this immune pathway. Impact statement Our article is focused on emerging pathogenetic pathways in systemic lupus erythematosus (SLE). Notably, IL-12 and IL-23 have been described as emerging cytokines in SLE pathogenesis. We know that IL-23 stimulates Th17 cells to produce IL-17. We try to point out the importance of IL-23/Th17 axis in SLE and to focus on the interaction between this axis and IL-12. Ustekinumab, a fully human IgG1κ monoclonal antibody directed towards the p40 shared subunit of IL-12 and IL-23, has been recently investigated in SLE, suggesting a potential novel therapeutic strategy in SLE. To our knowledge, there are no reviews which simultaneously focus on IL-12 an IL-23/Th17 axis in SLE. Thus, we believe our work will be of interest to the readers.

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Section: Il-17 In Slementioning

confidence: 92%

Section: Il-17 In Slementioning

confidence: 99%

IL-12 and IL-23/Th17 axis in systemic lupus erythematosus

Larosa

Zen

Gatto

et al. 2019

Exp Biol Med (Maywood)

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“…Multiple options are available for the treatment of active PsA, including nonsteroidal anti-inflammatory drugs (NSAIDs), conventional synthetic disease-modifying anti-rheumatic drugs (DMARDs), and biologic therapies such as tumor necrosis factor-α inhibitors (TNFi; e.g., adalimumab, certolizumab pegol, etanercept, golimumab, and infliximab) [8, 9]. Recently, additional new therapies for PsA have been introduced to the market, including an oral phosphodiesterase 4 inhibitor (i.e., apremilast) [10] and targeted immunomodulators that interact with pathways other than TNF-α (e.g., abatacept, ixekizumab, secukinumab, ustekinumab, and tofacitinib) [11–14]. The overall goals of treatment are to control inflammation, reduce pain and discomfort, and prevent joint degeneration and disability [15].…”

Section: Introductionmentioning

confidence: 99%

Economic Burden of Switching to Different Biologic Therapies Among Tumor Necrosis Factor Inhibitor-Experienced Patients with Psoriatic Arthritis

Song

Betts

et al. 2019

Rheumatol Ther

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Introduction Patients with psoriatic arthritis (PsA) who receive an initial tumor necrosis factor inhibitor (TNFi) may switch to another TNFi or a non-TNFi biologic therapy. This study compared the healthcare resource use (HRU), expenditures, and time to discontinuation among TNFi-experienced patients with PsA who switched to different biologic therapies in the United States (US). Methods Adults with PsA who discontinued an initial TNFi (adalimumab, etanercept, infliximab, golimumab, or certolizumab pegol) and switched to another TNFi or a non-TNFi (ustekinumab or secukinumab) were identified in the Symphony Health Solutions database [Quarter (Q)1 2010–Q2 2017]. Eligible patients had claims data activity for ≥ 12 months before (baseline) and after (study period) the switching date. All-cause HRU, costs (2017 US dollars), and time to discontinuation during the study period were compared between patients switching to another TNFi vs. a non-TNFi (index drug). Multivariable regression models adjusted for baseline covariates (index year, age, sex, initial TNFi, comorbidities, baseline HRU, and PsA-related treatment history). Results Of 2107 patients switching to another TNFi and 253 switching to a non-TNFi, adalimumab and etanercept were the most common initial TNFi in both cohorts. During the study period, patients switching to another TNFi had significantly fewer dermatologists visits (0.43; p < 0.01) but more rheumatologist visits (1.56, p < 0.01) than patients switching to a non-TNFi. Patients switching to another TNFi vs. a non-TNFi incurred significantly lower total average healthcare expenditures (adjusted difference: $17,625; p < 0.01), driven by lower prescription drug (adjusted difference: $17,172; p < 0.01) and hospitalization expenditures (adjusted difference: $5772; p = 0.04). Patients who switched to another TNFi vs. a non-TNFi continued on their index therapy significantly longer (median time to discontinuation: 8.31 vs. 5.68 months; log-rank p < 0.01). Conclusions Patients with PsA who switched to another TNFi had lower total healthcare expenditures and longer persistence compared with patients who switched to a non-TNFi biologic. Funding AbbVie.

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“…Numerous studies have demonstrated promising therapeutic effects in certain autoimmune diseases by targeting IL-23/IL-17 axis, mostly through using Abs against IL-23 or IL-17A (5-7). For example, pharmaceutical companies have been testing Ab drugs targeting IL-17A, p40 subunit of IL-23 and IL-12, as well as p19 subunit of IL-23 in psoriasis, rheumatoid and psoriatic arthritis, autoimmune uveitis, and multiple sclerosis (8)(9)(10)(11)(12). To date, the Ab drugs that specifically neutralize IL-23 or IL-17A have shown remarkable effectiveness for the treatment of psoriasis (13).…”

mentioning

confidence: 99%

“…To date, the Ab drugs that specifically neutralize IL-23 or IL-17A have shown remarkable effectiveness for the treatment of psoriasis (13). In fact, ustekinumab (anti-p40 of IL-12 and IL-23) and tildrakizumab (anti-IL-23p19) have been successfully used to treat psoriatic diseases (9,11,12). Ixekizumab and secukinumab, two Abs against IL-17A, have also shown similar safety profiles and therapeutic efficacy (14)(15)(16)(17).…”

mentioning

confidence: 99%