An RDBPCT (“type”:”clinical-trial”,”attrs”:”text”:”NCT05129423″,”term_id”:”NCT05129423″NCT05129423) is enrolling individuals to evaluate MTPS9579A as a treatment for refractory CSU [69]. 3.9.3. pathways, have been used off-label in case series while others are under investigation in RCTs. Most of them have showed promising results. Conclusions: Omalizumab remains the best choice to treat refractory CSU. Although results from additional mAbs seem to be motivating to achieve sign control in refractory CSU, thus improving patients QoL, RCTs are needed to confirm their performance and security. [25]Phase 2 RDBPCT[26]RDBPCT[27]Phase 3 RDBPCT[28]RDBPCT[29]Phase 3 RDBPCT ASTERIA I31941[30]Phase 3[31]RDBPCT[32]Phase 3[33]RDBPCT[34]Open-label + RDBPCT[35]Phase 3 RCT [36]RDBPCT41818CSU refractory to H1AH[37]Phase 2b[38]Open-label extension study of “type”:”clinical-trial”,”attrs”:”text”:”NCT02477332″,”term_id”:”NCT02477332″NCT0247733222644.5 12.7[39]Open-label extension study of “type”:”clinical-trial”,”attrs”:”text”:”NCT02477332″,”term_id”:”NCT02477332″NCT0247733222644.5 12.7[40]Phase 2[41]RDBPCT= 0.17)= 0.24)NoNo Mepolizumab Authors Type of study N. Age (Yrs) Indication Dose Duration Follow-Up Results Adverse events Beneficial Magerl et al. 2018[42]Case statement127Severe refractory[43]Case statement143Severe refractory[44]Solitary- blind trial1247.3 1.3CSU refractory to H1AH[45]Case series636.2[46]Case series26C17Inadequate response to H1AH, omalizumab (450 or 600 mg), and cyclosporine300 mg[47]Case series252C63CSU refractory to H1AH, LTRA, methotrexate, omalizumab, cyclosporine[48]Case statement112CSU refractory to H1AH[49]Case statement151CSU refractory to H1AH, H2AH, CSS, cyclosporine, mycophenolate mofetil375 mg/m2 weekly[50]Case statement138CSU refractory to H1AH and ASP6432 CSS1000 mg[51]Case statement144Antisynthetase syndrome and CSU refractory to H1AH and [52]Case series8NRCSU refractory to H1AH, omalizumab, CSS, [53]Phase 2[54]Case statement135CSU refractory to H1AH[25]Phase 2 RDBPCT[26]RDBPCT[27]Phase 3 RDBPCT[28]RDBPCT[29]Phase 3 RDBPCT ASTERIA I31975 mg, 150 mg, [30]Phase 3[32]Phase 3[37]Phase 2b[39]Open-label extension study of “type”:”clinical-trial”,”attrs”:”text”:”NCT02477332″,”term_id”:”NCT02477332″NCT02477332226240 mg Q4WWeek 12UAS7 = 0 (41.6%)”type”:”clinical-trial”,”attrs”:”text”:”NCT03437278″,”term_id”:”NCT03437278″NCT03437278[40]Phase 2[45]Case series6600 mg loading dose, 0.05). Table 4 ASP6432 List of the studies on biologics in CSU reporting the HR-QoL score as an end result. [26]RDBPCT[27]Phase 3 RDBPCT[29]Phase 3 RDBPCT ASTERIA I319300 mg [30]Phase 3[32]Phase 3[34]Open-label + RDBPCT[37]Phase 2b[38]Open-label extension study of “type”:”clinical-trial”,”attrs”:”text”:”NCT02477332″,”term_id”:”NCT02477332″NCT02477332226240 mg Q4WWeek 52 DLQI (?9.52)”type”:”clinical-trial”,”attrs”:”text”:”NCT03437278″,”term_id”:”NCT03437278″NCT03437278[40]Phase 2 0.05). We also included 17 ongoing or completed clinical tests on the use of mAbs in CSU (Table 5) [55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71]. Table 5 List of the ongoing tests investigating mAbs in treating CSU. Ligelizumab Trial Quantity Type of Study Status N. Age (Yrs) Inclusion Criteria Dosage Period Follow-Up “type”:”clinical-trial”,”attrs”:”text”:”NCT03907878″,”term_id”:”NCT03907878″NCT03907878[55]Phase 3[56]Phase 3[57]Phase 1[58]Phase 3[59]Phase 3[60]Phase 1[61]Phase 1[62]Phase 2[63]Phase 2a[64]Phase 3[65]Phase 1C2[66]Phase 2b[67]Phase 1[68]Phase 2[69]Phase 2[70]Phase 2[71]Phase 2 Rabbit polyclonal to AGAP 0.001 and = 0.047, respectively), while the 75 ASP6432 mg dose induced a non-significant switch in UAS7 compared with the placebo. A plateau in doseCresponse was observed with around 300 mg omalizumab [25]. The authors suggested that the earlier onset of action in CSU than in asthma could be explained by lower total IgE levels and less-dependent IgE pathogenesis [25]. The switch in UAS7 ASP6432 from baseline to week 24 was also significant in individuals with moderate-to-severe CSU and positive IgE anti-TPO antibodies, which are probably involved in mast-cell degranulation, after omalizumab vs. placebo (?17.8 vs. ?7.9 points; = 0.0089). Two-thirds of individuals in the treatment group reached the resolution of symptoms [26]. These tests paved the way for the development of further RCTs on larger populations. Among these, the results of three RDBPCTs, GLACIAL, ASTERIA I, and ASTERIA II, led to the authorization of omalizumab for the treatment of CSU by the Food and Drug Administration (FDA) [27,28,29]. GLACIAL assessed the security of omalizumab 300 mg like a main endpoint, enrolling 335 individuals with CSU refractory to H1AH at up to four-fold the authorized dose in combination with H2 antihistamines (H2AH) and/or leukotriene receptor antagonists (LTRAs). No difference in the pace of AEs was found between the treatment and placebo organizations over 40 weeks (11% vs. 13%) [26]. The changes reported in weekly itch severity score (ISS7) at week 12 were significant (?8.6 vs. ?4.0 points; 0.001), while similarly found for UAS7 and the dermatological quality of life index (DLQI) [27]. In ASTERIA I ASP6432 and II, in.