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Dermatoses of Pregnancy
Published in Vincenzo Berghella, Maternal-Fetal Evidence Based Guidelines, 2022
Hannah J. Anderson, Dana Correale, Jason B. Lee
When IH is insufficiently controlled with CS alone, the next therapeutic option is cyclosporine A (CsA). Doses of 3–10 mg/kg/day have been reported in the treatment of IH [60–62]. Again, medication should be tapered to the lowest possible dose that results in control of the disease. The mechanism of action is inhibition of calcineurin with resultant decrease in interleukin-2 production by CD4+ T cells. CsA also inhibits interferon-γ production by T cells. CsA is pregnancy category C. The most serious adverse effects are renal dysfunction and hypertension [16]. Renal function and blood pressure should be monitored during therapy. In a study of transplant recipients treated with CsA during pregnancy there was no evidence of teratogenicity [63]. However, 44.5% of infants were born at less than 37 weeks’ gestation and 44.3% weighed less than 2500 g at birth [63]. CsA is excreted in human breast milk and breastfeeding should be avoided during therapy. Biologic therapies may be considered as an alternative to cyclosporine or next-in-line therapy. Tumor necrosis factor (TNF) α inhibitors and ustekinumab are pregnancy category B drugs. As no significant pregnancy adverse outcomes have been observed, TNFα inhibitors such as infliximab may be considered, even as the first-line therapy [64]. No human safety data during pregnancy are available for newer biologic agents such as brodalumab, ixekizumab, guselkumab, secukinumab, and tildrakizumab, but animal studies showed no adverse effects [16].
Bayesian Methods for Evaluating Drug Safety with Real-World Evidence
Published in Harry Yang, Binbing Yu, Real-World Evidence in Drug Development and Evaluation, 2021
Based on the background suicidal incidence rate estimated from the meta-analysis, the probabilities of observing a certain number of suicidal cases for the two clinical trials for brodalumab are shown in Table 5.8. At the study duration of 54+ weeks, there are 975 patients who receive a 210-mg constant dose Q2W and the total exposure time is 781.2 person-year; the posterior mean probability of observing two suicidal subjects or more is . The corresponding probability for the one case at week 12 is 0.138. Therefore, given the higher background risk of suicidal attempts among the psoriasis patients, it is possible that even though the use of brodalumab did not cause additional risk of suicide, we may still observe two or more suicidal attempts in the AMAGINE-2 and AMAGINE-3. In addition, multiple AEs are monitored in the safety analysis; the chance of an AE being statistically significant is even higher due to multiple testing. Note that the one subject at week 54 attempted suicide three times. If we count the three suicidal attempts as independent, we may observe four suicidal attempts by week 54. The probability of observing four or more cases is 0.0013. This may indicate a possibility of brodalumab causing suicide. However, this probability estimate is extremely conservative as the multiple suicidal attempts for the same individual are strongly correlated.
Bronchus-associated lymphoid tissue and immune-mediated respiratory diseases
Published in Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald, Principles of Mucosal Immunology, 2020
Dale T. Umetsu, Bart Lambrecht
Brodalumab (Amgen/Valeant), by targeting IL-17RA, which is utilized by both IL-17 and IL-25, blocks the effects of IL-17 and IL-25. Brodalumab has been approved by the FDA for plaque psoriasis. It has also been studied for asthma, but early studies suggest minimal effect in patients with moderate to severe asthma.
Biological treatment for erythrodermic psoriasis
Published in Expert Opinion on Biological Therapy, 2022
Brodalumab binds with high affinity to IL-17 receptor and inhibits the action of multiple pro-inflammatory cytokines (IL-17A, IL-17C, IL-E, IL-17F, and IL-A/F). In a 52-week, open-label study of 18 EP patients treated with brodalumab, mean PASI improvement was 48.03%, 85.06%, and 93.41% at weeks 2, 12, and 52, respectively [58]. No serious adverse effects were noted and the efficacy was maintained at 52 weeks. Real-world efficacy of brodalumab was reported by Megna et al. in two patients of acute EP precipitated by withdrawal of systemic steroids and cyclosporine [59]. A rapid response was observed without any adverse effects. Successful use of brodalumab in an EP patient with secondary biologic failure to ustekinumab has been described [60]. A rebound phenomenon after discontinuation of brodalumab has been described, with disease flare (including pustular and EP) on discontinuation of therapy [61]. Abrupt cessation of therapy is hence not advisable, even in patients who achieve complete clearance of psoriatic lesions.
Modeling the optimal sequence of biologic therapies in plaque psoriasis in Spain
Published in Journal of Medical Economics, 2021
Alexander Egeberg, Anne Danø, Mikkel H. Pedersen, Anne Sohrt, Emma Borg, Jaime Notario
When a full analysis of the 840 different treatment sequences was conducted, brodalumab was chosen as the first-line therapy in all the top 81 most cost-effective treatment sequences. This is because brodalumab has a high efficacy rate and a per-patient cost that is close to the median cost of all the available alternatives. Another important factor when determining the most cost-effective choice of first-line therapy is the higher cost of treatment during the induction period. By comparing the cost of treatment using brodalumab during the first year with the cost of treatment using brodalumab in future years, as presented in Table 1, it was seen that the induction period implied an added cost of €1,050, corresponding to a 7.7% increase. In contrast to this, the incremental cost of treatment during the first year with risankizumab was €7,667 higher as compared with the cost of treatment using risankizumab in future years, corresponding to a 50% increase.
Role of IL-17 in asthma pathogenesis and its implications for the clinic
Published in Expert Review of Respiratory Medicine, 2019
Rakhee K Ramakrishnan, Saba Al Heialy, Qutayba Hamid
Secukinumab, a fully humanized monoclonal antibody (mAb) selectively targeting IL-17A, have shown improved clinical efficacy in the treatment of plaque psoriasis [89], psoriatic arthritis [90,91], RA [92], ankylosing spondylitis [93], leading to its FDA approval for the treatment of moderate-to-severe plaque psoriasis, active psoriatic arthritis and ankylosing spondylitis [94]. Ixekizumab is another anti-IL-17A mAb indicated for the treatment of moderate-to-severe plaque psoriasis and active psoriatic arthritis [95,96]. Brodalumab is an IL-17RA antagonist that blocks the downstream signaling of IL-17A, IL-17F, IL-17A/F and IL-17E (IL-25). Brodalumab is indicated for the treatment of moderate-to-severe plaque psoriasis in adult patients [97]. Other potential candidates targeting IL-17 being tested in clinical trials, primarily on autoimmune diseases, include CNTO 6785 (anti-IL-17A mAb) [98], ABT-122 (IL-17A and TNF-α bispecific dual variable domain immunoglobulin) [99,100], COVA322 (bispecific IL-17A/TNF-α inhibitor) [101], ALX-0761 (Anti-IL-17A/F bispecific nanobody) [102], Bimekizumab (Anti-IL-17A/F bispecific mAb) [103], NI-1401 (Anti-IL-17A/F bispecific mAb) [104] and SCH 900,117 [105].