Dataset Information

Long-term efficacy and safety results from an open-label phase III study (UNCOVER-J) in Japanese plaque psoriasis patients: impact of treatment withdrawal and retreatment of ixekizumab.

ABSTRACT: BACKGROUND:Long-term management of moderate-to-severe psoriasis is usually discussed in terms of continuous administration; however, there are many situations in clinical practice where treatment may be withdrawn with subsequent retreatment. OBJECTIVE:To assess the clinical course after ixekizumab treatment withdrawal and retreatment, as well as the effectiveness of ixekizumab retreatment, in Japanese patients with plaque psoriasis. METHODS:This single-arm, open-label study (UNCOVER-J; NCT01624233) comprised 78 patients with plaque psoriasis. After ixekizumab treatment (160-mg loading dose, 80 mg every 2 weeks for the first 12 weeks, and then 80 mg every 4 weeks (IXE Q4W) until Week 52), 70 patients achieved a Psoriasis Area Severity Index (PASI)75 response at Week 52. These 70 patients withdrew from ixekizumab treatment from Weeks 52 to 100. Patients who relapsed (PASI ?50) during the Treatment Withdrawal Period were retreated with IXE Q4W for 192 weeks. RESULTS:At Weeks 52, 76 and 100, PASI75 response rates were 100%, 26% and 7%; PASI90 response rates were 87%, 11% and 3%; and PASI100 response rates were 53%, 0% and 0%. After treatment withdrawal, 87% of patients relapsed; median time to relapse was 143 days. After 12 weeks of retreatment with IXE Q4W, 83% of relapsed patients achieved PASI75, 68% achieved PASI90 and 25% achieved PASI100; improvements were maintained up to 120 weeks of retreatment. Treatment-emergent adverse events and serious adverse events were reported in 56% and 4% of patients during the Treatment Withdrawal Period, and in 88% and 14% of patients during the Retreatment Period. CONCLUSION:In patients withdrawn from ixekizumab after achieving PASI75, approximately half relapsed within 5 months of withdrawal; however, most patients recaptured response within 12 weeks, and response was maintained for up to 120 weeks of retreatment.

SUBMITTER: Umezawa Y

PROVIDER: S-EPMC6587494 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Long-term efficacy and safety results from an open-label phase III study (UNCOVER-J) in Japanese plaque psoriasis patients: impact of treatment withdrawal and retreatment of ixekizumab.

Umezawa Y Y Torisu-Itakura H H Morisaki Y Y ElMaraghy H H Nakajo K K Akashi N N Saeki H H

Journal of the European Academy of Dermatology and Venereology : JEADV 20181113 3

<h4>Background</h4>Long-term management of moderate-to-severe psoriasis is usually discussed in terms of continuous administration; however, there are many situations in clinical practice where treatment may be withdrawn with subsequent retreatment.<h4>Objective</h4>To assess the clinical course after ixekizumab treatment withdrawal and retreatment, as well as the effectiveness of ixekizumab retreatment, in Japanese patients with plaque psoriasis.<h4>Methods</h4>This single-arm, open-label study ...[more]

PMID: 30325534

Similar Datasets

Project description:BackgroundErythrodermic and generalized pustular psoriasis are rare, difficult to treat forms of psoriasis. In previous reports, we documented 24- and 52-week findings of an open-label, phase 3 trial (UNCOVER-J) of ixekizumab in Japanese patients with erythrodermic or generalized pustular psoriasis; most patients responded to treatment and maintained response through 52 weeks.ObjectiveTo assess the long-term (>3 years) efficacy and safety of ixekizumab in Japanese patients with erythrodermic or generalized pustular psoriasis.MethodsThese subgroup analyses were of a partial population of patients from UNCOVER-J (NCT01624233; Sponsored by Eli Lilly and Company), specifically those with erythrodermic psoriasis (N = 8) or generalized pustular psoriasis (N = 5). These patients received 160 mg ixekizumab at Week 0, ixekizumab 80 mg every 2 weeks through Week 12, and ixekizumab 80 mg every 4 weeks thereafter up to Week 244. This regimen is consistent with the regimen approved in Japan for plaque, erythrodermic, and generalized pustular psoriasis and psoriatic arthritis. Efficacy assessments included Global Improvement Score (GIS), Psoriasis Area and Severity Index (PASI), dermal symptoms (for patients with generalized pustular psoriasis), Dermatology Life Quality Index (DLQI) and Itch Numeric Rating Scale (NRS). Safety assessments included treatment-emergent adverse events and adverse events of special interest.ResultsMost patients had a GIS of resolved or improved from Week 12 onwards, and all patients had early and sustained improvement in PASI and dermal symptom (generalized pustular psoriasis only) scores. Mean improvements in DLQI and Itch NRS at Week 12 were sustained through Week 244. Ixekizumab was well tolerated over 3 years of treatment in patients with erythrodermic psoriasis or generalized pustular psoriasis, and no new safety concerns were identified.ConclusionThese findings suggest that ixekizumab can be an effective long-term treatment option for erythrodermic or generalized pustular psoriasis.

Project description:Brodalumab, an interleukin-17 receptor A inhibitor, demonstrated rapid and robust efficacy with a favorable safety profile in patients with moderate to severe plaque psoriasis. Here, we present data from a multicenter, open-label extension study in patients with plaque psoriasis with/without psoriatic arthritis who completed 64 weeks of treatment with brodalumab (140 or 210 mg, every 2 weeks [Q2W]). Patients were enrolled to evaluate the long-term safety and efficacy of a modified dose of brodalumab. Eligible patients were switched to a reduced dose of brodalumab (140 mg every 4 weeks on day 1) in the extension study; the dose and dosing interval were modified sequentially at the physician's discretion (minimum 140 mg every 8 weeks and maximum 210 mg Q2W) until drug approval, after which all patients were switched to 210 mg Q2W for postmarketing surveillance. Of the 129 patients enrolled, 107 (82.9%) completed the 108-week or more extension study. All patients had psoriasis that was well controlled with brodalumab treatment on day 1. Improvement in psoriasis-related symptoms, evaluated with the Psoriasis Area and Severity Index, Psoriasis Scalp Severity Index, Dermatology Life Quality Index, Nail Psoriasis Severity Index, and American College of Rheumatology 20, 50 and 70, was maintained during the 108-week extension study. Brodalumab treatment was well tolerated throughout, and no new safety signals were identified. The most commonly reported treatment-related adverse event was nasopharyngitis, followed by influenza and oral candidiasis. No cases of serious candida infection or Crohn's disease were observed in this study. Serious treatment-related adverse events, such as appendicitis, brain abscess, bacterial meningitis, colon cancer, immunoglobulin A nephropathy and tubulointerstitial nephritis, were reported in one patient each. No anti-brodalumab-binding antibodies or brodalumab-neutralizing antibodies were detected in any patient throughout the extension study. Overall, the long-term efficacy and safety of brodalumab were demonstrated over 108 weeks.

Project description:The efficacy of ixekizumab, an anti-interleukin-17A (anti-IL-17A) monoclonal IgG4 antibody, was demonstrated in moderate-to-severe psoriasis patients when administered via prefilled syringe (PFS).To evaluate the effect of two drug delivery devices on the pharmacokinetics (PK) of ixekizumab as well as efficacy and safety with both devices.In the first 12 weeks of an open-label, phase 3 study, moderate-to-severe psoriasis patients were randomized to ixekizumab delivery via PFS or autoinjector device. Randomization was stratified by weight (<80 kg, 80-100 kg, >100 kg), injection assistance (yes/no) and injection site (arm, thigh or abdomen). Following a 160-mg initial dose at week 0, patients received subcutaneous 80-mg ixekizumab as a single injection every 2 weeks for 12 weeks. Blood samples were collected following the initial 160-mg dose on days 2, 4, 7, 10 and 14 for PK analysis. Primary PK parameters were maximum concentration (Cmax ) and area under the curve (AUC0-tlast ) where tlast is the time of last sample (14 days ± 24 h). Efficacy was assessed by percent improvement on the Psoriasis Area and Severity Index (PASI) at week 12. Adverse event reporting, vital signs and clinical laboratory data were used to evaluate safety.Of 204 randomized patients, 192 were included in the PK analysis (PFS: 94; autoinjector: 98). The PFS and autoinjector showed similar geometric mean Cmax (90% CI) [15.0 ?g/mL (13.9-16.1) vs. 14.8 ?g/mL (13.8-15.9)] and geometric mean AUC0-tlast (90% CI) [157 ?g × day/mL (147-168) vs. 154 ?g × day/mL (144-165)]. When comparing Cmax and AUC0-tlast of the autoinjector to PFS, the geometric LS mean ratios were 0.97. At week 12, mean percent PASI improvement (via modified baseline observation carried forward) was similar with the PFS (89.3%) and autoinjector (86.9%). Both devices had safety results that were consistent with the known safety profile of ixekizumab.The PK, efficacy and safety of ixekizumab administered subcutaneously by PFS and autoinjector were similar. Clinicaltrials.gov number: NCT01777191 https://clinicaltrials.gov/ct2/show/NCT01777191.

Dataset Information

Long-term efficacy and safety results from an open-label phase III study (UNCOVER-J) in Japanese plaque psoriasis patients: impact of treatment withdrawal and retreatment of ixekizumab.

Publications

Long-term efficacy and safety results from an open-label phase III study (UNCOVER-J) in Japanese plaque psoriasis patients: impact of treatment withdrawal and retreatment of ixekizumab.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets