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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].
Targeting IL-23/IL-17 Axis for Treatment of Psoriasis and Psoriatic Arthritis
Published in Siba P. Raychaudhuri, Smriti K. Raychaudhuri, Debasis Bagchi, Psoriasis and Psoriatic Arthritis, 2017
Subhashis Banerjee, Philip Mease
This is a humanized IgG1 antibody that neutralizes IL-23 p19 [24]. Results from two Phase 3 trials (ReSURFACE 1 and 2) in psoriasis were recently disclosed [25]. The two trials included 1862 patients with moderate to severe plaque psoriasis. In the trials, the agent dosed at weeks 0 and 4, and then quarterly at 100 or 200 mg, achieved PASI 75 response rates of 63%–64% at week 12 and 77%–80% at week 28 (placebo 3%–6%). The data further showed that more patients on tildrakizumab achieved higher skin responses (PASI 90 and 100) than those on placebo and etanercept. PASI 90 responses were achieved by 36%–37% at week 12, which increased to 54%–59% at week 28, and an average of 13% achieved PASI 100 at week 12, which increased to 24%–30% at week 28 at the two doses. The overall safety profile of tildrakizumab was consistent with previously reported studies with no significant findings. There are no available data for this agent in PsA, although there were numerical improvements in some PsA measures (Psoriatic Arthritis Screening and Evaluation [PASE], HAQ, and pain) in a small sample of patients with chronic plaque psoriasis who had concomitant PsA (18%) in the Phase 2b study [26].
Biologic therapies in the pipeline
Published in M. Alan Menter, Caitriona Ryan, Psoriasis, 2017
Molly Campa, Pablo Michel, Caitriona Ryan
Tildrakizumab (MK-3222) (Merck, Kenilworth, New Jersey) is a humanized IgG1k, anti-IL-23p19 monoclonal antibody.18 A three-part, randomized, double-blind, phase IIb trial demonstrated that tildrakizumab was superior to placebo in treating moderate-to-severe plaque psoriasis. Participants were randomized to receive subcutaneous tildrakizumab (5, 25, 100, or 200 mg) or placebo at weeks 0 and 4 and then every 12 weeks until week 52.18 At week 16, the PASI 75 response rate was significantly greater for all doses of the tildrakizumab group compared with placebo: 33.3% on 5 mg, 64.4% on 25 mg, 66.3% on 100 mg, and 74.4% on 200 mg, versus 4.4% in the placebo group.18 The drug was withdrawn at week 52, and subjects were followed until week 72. Tildrakizumab showed a low rate of relapse during the 20-week nontreatment period, with only 3.6% of responders relapsing before week 72.18
Real-world practice indirect comparison between guselkumab, risankizumab, and tildrakizumab: results from an Italian 28-week retrospective study
Published in Journal of Dermatological Treatment, 2022
Matteo Megna, Nello Tommasino, Luca Potestio, Teresa Battista, Angelo Ruggiero, Matteo Noto, Gabriella Fabbrocini, Lucia Genco
An Italian single-center retrospective observational study enrolling moderate-to-severe psoriasis patients attending the Psoriasis Care Center of the University of Naples Federico II, Italy, from November 2019 to November 2021 was performed to compare the efficacy and safety in real-life of guselkumab, tildrakizumab, and risankizumab, particularly focusing on difficult to treat areas. Inclusion criteria were: (i) age ≥18 years, (ii) moderate-to-severe plaque psoriasis, (iii) clinical manifestations in at least one of the so-called difficult-to-treat areas among scalp, palms and soles, nails, lower limbs, and genitals, and (iv) patients treated with guselkumab, tildrakizumab, or risankizumab. Patients were treated with a standard dose of guselkumab (100 mg administered by subcutaneous injection at Week 0 and Week 4, and then a maintenance dose every 8 weeks) or tildrakizumab (100 mg administered by subcutaneous injection at Week 0 and Week 4 followed by a maintenance dose every 12 weeks) or risankizumab (two injections of 75 mg subcutaneously at Week 0, Week 4, and then every 12 weeks).
IL-23 in axial spondyloarthritis and psoriatic arthritis: a good fit for biological treatment?
Published in Expert Opinion on Biological Therapy, 2022
Fabiola Atzeni, Cesare Siragusano, Ignazio Francesco Masala, Antonio Carriero, Valentina Picerno, Salvatore D’Angelo
A double-blind, placebo-controlled, phase IIb trial randomized 391 patients to receive Tildrakizumab (200 mg every 4 weeks, 200 mg every 12 weeks, 100 mg every 12 weeks, or 20 mg every 12 weeks) or placebo. At week 24, ACR20 primary endpoint was achieved by 71.4%–79.5% of patients treated with Tildrakizumab versus 50.6% of placebo group. Patients treated with Tildrakizumab achieved higher rates of ACR50/70, MDA and PASI improvement, while no significant improvement was observed in dactylitis and enthesitis scores. A low rate of adverse events was observed in Tildrakizumab treated patients. Nasopharyngitis and diarrhea have been the most frequent events, and no cases of candidiasis, inflammatory bowel disease, active tuberculosis or other opportunistic infection were reported [94].
Comparison of psoriasis guidelines for use of IL-23 inhibitors in the United States and United Kingdom: a critical appraisal and comprehensive review
Published in Journal of Dermatological Treatment, 2022
R. I. Ghamrawi, N. Ghiam, J. J. Wu
The recommended induction dose of tildrakizumab is 100 mg subcutaneous injection at weeks 0 and 4 followed by maintenance dosing every 12 weeks thereafter (3,8–11). In certain patients, according to NICE guidelines, such as those with higher disease burden or body weight (90 kg or more), a 200 mg dose may be more efficacious (9). In phase III clinical trials for the management of moderate-to-severe plaque psoriasis in adults, tildrakizumab proved effective at dosages of 100 mg or 200 mg at weeks 0 and 4 and every 12 weeks thereafter (21). In a phase III RCT of 1090 patients (reSURFACE 2), participants were randomized to receive either tildrakizumab 100 mg, tildrakizumab 200 mg, etanercept, or placebo. A greater proportion of patients receiving tildrakizumab 100 mg (39%) achieved PASI 90 compared to tildrakizumab 200 mg (37%), etanercept (21%), and placebo (1%) (21). BAD guidelines recommend escalating the dose of tildrakizumab therapy in adults when an inadequate primary response is proposed due to insufficient drug exposure. In such patients, tildrakizumab dosing should be increased from the recommended 100 mg to 200 mg every 12 weeks (8). Currently, a dose-escalation strategy is only available for tildrakizumab. NICE guidelines recommend the discontinuation of tildrakizumab between 12 weeks and 28 weeks if a 50% or greater reduction in PASI score remains unachieved; tildrakizumab should also be stopped at 28 weeks if adequate response remains unachieved. As with guselkumab, adequate response is defined by achievement of PASI 75 or PASI 50 and a five-point reduction in DLQI (9).