Objectives To evaluate the efficacy of guselkumab through four years of continuous treatment for psoriasis.Methods In the phase 3 VOYAGE 1 trial, 837 patients with moderate-to-severe psoriasis were randomized to receive guselkumab 100 mg every-8-weeks, placebo, or adalimumab 40 mg every-2-weeks. Patients in the placebo and adalimumab groups crossed over to receive guselkumab at weeks 16/52, respectively; eligible patients received open-label guselkumab through week 204. Efficacy endpoints (i.e., PASI 75/90/100, IGA 0/1, and IGA 0) were analyzed in the guselkumab group using different methodologies: prespecified treatment failure rules (TFR, patients discontinued due to lack of efficacy, psoriasis worsening, or protocol-prohibited psoriasis treatment considered nonresponders); nonresponder imputation (NRI, patients with missing data counted as nonresponders); and As Observed (OBS, no imputation). Safety was evaluated through week 204.Results At week 204, PASI 90 response rates were 82.2%, 68.4%, and 84.3%, respectively, based on TFR, NRI, and OBS analyses; corresponding proportions at week 52 were 79.7%, 75.5%, and 80.6%. Similarly, PASI 75, PASI 100, IGA 0/1, and IGA 0 responses were maintained from week 52 through week 204. No new safety signals were identified.Conclusions High efficacy response rates were maintained through four years of continuous guselkumab treatment for psoriasis.
Objective:To use data from a phase II clinical trial to evaluate the effect of ustekinumab, a human immunoglobulin monoclonal antibody that binds with high affinity to the shared p40 subunit of human interleukins-12 and -23, on physical disability and health-related quality of life (HRQoL) in patients with psoriatic arthritis (PsA).Methods:In this multicenter, double-blind, placebo-controlled, crossover study of ustekinumab, patients with active PsA were randomized (1:1 ratio) to receive either ustekinumab at weeks 0, 1, 2, and 3 and placebo at weeks 12 and 16 (n = 76) or placebo at weeks 0, 1, 2, and 3 and ustekinumab at weeks 12 and 16 (n = 70). Physical function was assessed using the disability index from the Health Assessment Questionnaire-Disability Index (HAQ-DI) in all randomized patients. HRQoL was evaluated using the Dermatology Life Quality Index (DLQI) in a subset of patients (84.9%) with at least 3% body surface area (BSA) psoriasis involvement at baseline.Results:At baseline, overall mean HAQ-DI and DLQI scores were 0.9 and 11.5, respectively, indicating impaired physical function and moderate effect on HRQoL. At week 12, ustekinumab patients had significantly more improvement (decrease) in the mean HAQ-DI (−0.31) and DLQI (−8.6) scores versus placebo (−0.04 and −0.8, respectively; p < 0.001 for both comparisons). At week 12, 58.7% (37/63) of ustekinumab-treated patients had a DLQI score of 0 or 1 (no negative effect of disease or treatment on HRQoL) versus 5.5% (3/55) for placebo (p < 0.001). The results also indicated a positive but weak correlation between improvement in physical function and HRQoL, pain, and skin response as well as between improvement in joint and skin responses in patients receiving ustekinumab or placebo. Potential limitations of the study include the short duration of the placebo-controlled period and the relatively small patient population.Conclusion:Ustekinumab significantly improved physical function and HRQoL in patients with PsA and psoriasis involving at least 3% BSA.
Due to the chronic nature of psoriasis, it is important to assess the sustained response of treatments over time.To assess the efficacy of continuous treatment with guselkumab (an interleukin-23 blocker) through two years in the phase 3 VOYAGE 1 trial.Patients were randomized to placebo, guselkumab, or adalimumab at baseline. Placebo-randomized patients crossed over to guselkumab at week 16 (placebo→guselkumab) and adalimumab-randomized patients crossed over to guselkumab at week 52 (adalimumab→guselkumab); all patients received open-label guselkumab beyond week 52. Efficacy was assessed based on the Psoriasis Area and Severity Index (PASI; proportion of patients achieving ≥75%, 90%, or 100% improvement [PASI 75/90/100]) and the Investigator's Global Assessment (IGA; proportion achieving nearly clear [IGA 0/1] or completely clear [IGA 0]). As pre-specified, efficacy data were analyzed using non-responder imputation (NRI; patients with missing data counted as non-responders) after applying treatment failure rules (TFR; patients meeting TFR counted as non-responders thereafter) through week 48 and by applying TFR only from week 52 through 100. All endpoints were also analyzed using NRI and As Observed methodology for the guselkumab group through week 100.The clinical responses were maintained through week 100 based on all three analyses. Based on pre-specified analyses, proportions of patients who achieved PASI 75, PASI 90, PASI 100, IGA 0/1, and IGA 0 were 94.8%, 82.1%, 49.0%, 82.4%, and 53.8%, respectively, at week 100. Results were similar for the placebo→guselkumab and adalimumab→guselkumab groups at week 100. As expected, proportions of patients achieving these endpoints were similar based on As Observed analyses and slightly lower when the more conservative NRI rules were applied.High levels of efficacy were maintained through two years of continuous treatment among guselkumab-treated patients, and efficacy improved through two years among adalimumab-treated patients who crossed over to guselkumab at one year. J Drugs Dermatol. 2018;17(8):826-832.
Objective To explore the Quality of Life of 683 people with asthma in Jiangyin,Jiangsu,2008.Discuss the risk factors as well as the facts that affect the QL of asthma patients.Provide theory basis for the protection of asthma.Methods Investigated the people who have physical examination in jiangyin from Jan.1st to Dec.31st,2008.and figured out 981 persons who were dignosed(or suspiciously dignosed)asthma.And tested their PFT.Results 85761 people were investigated,of whom 683 were dignosed asthma,the morbidity rate was 0.80%,the male female ratio was 1.19 ∶1.The risk factors included hereditary,environment,individual quality and diet.70.1% people Of the 458 asthma patients didn′t know the signification of PFT before.During the past 1 month only 8.5%(39/458) people′s synptoms were completely controlled.52.6%(241/458)were partly controlled,38.9%(178/458)were out of control.The outcome of the investigation of the Management of asthma patients was not so good.Only 17% patients considered it necessary to be guided by doctors and take standard treatment.Conclusions This research represented the control situation of asthma in Jiangyin,Jiangsu.The relative data provided theory basis for the protection and futher research of asthma.
Ustekinumab(UST) is approved for moderate-to-severe psoriasis(PsO), and is currently in Phase 3 development for psoriatic arthritis(PsA).
Objectives
We report the long-term safety experience of UST in the sub-group of PsO pts with a medical history of PsA(PsA Sub-group) compared with the overall PsO population (Overall Population) from the PsO development program with up to 5yrs of treatment and follow-up.
Methods
Pooled safety data across one Phase 2 and three Phase 3[PHOENIX 1, PHOENIX 2, ACCEPT] clinical trials in pts with moderate-to-severe PsO were analyzed. Pts received UST45mg or 90mg SC 12wkly through up to 5yrs. The presence or absence of PsA (history of or current) at baseline was reported. No concurrent treatment for PsO or PsA was permitted throughout the studies, except for low potency topical steroids for PsO during the open-label long-term extensions of PHOENIX 1 and 2. Event rates for overall safety endpoints (adverse events [AEs], infections, AEs leading to discontinuation, serious AEs [SAEs]) and AEs of interest (serious infections, nonmelanoma skin cancers [NMSC], other malignancies, major adverse CV events [MACE]) were analyzed. All pts who received ≥1 dose of UST were included in the analyses. Data from the two UST dose groups were analyzed as a combined group. Results are expressed in events per 100 pt-years of follow-up (PY) and compared between the PsA Sub-group and Overall Population.
Results
The Overall Population included 3117pts (8998 PY) who received ≥1dose of UST;with 1482 (47.5%) pts treated for ≥4yrs or more (including 838 [26.9%] for ≥5yrs). At baseline, the majority of pts were white (92.2%), male (68.5%), median age of 46yrs. Mean BSA involvement was 26.2%±16.7 and mean PASI score was 19.7±7.7; 27.5% of pts had concomitant PsA. Safety results for the PsA Sub-group and Overall Population are detailed in Table 1. Through Yr5, event rates for overall safety endpoints and AEs of interest were generally comparable between the groups.
Conclusions
With continuous UST exposure for up to 5yrs and approximately 9000 pt-years of follow-up in the PsO development program, long-term safety in the Overall Population were consistent with previous reports at earlier follow-up and event rates were generally comparable to other currently approved biologic agents. Long-term safety in the sub-group of PsO patients with a history of PsA at baseline were generally comparable to those in the overall study population.
Disclosure of Interest
K. Papp Grant/research support from: Janssen Research & Development, LLC, C. Griffiths Grant/research support from: Janssen Research & Development, LLC, K. Gordon Grant/research support from: Janssen Research & Development, LLC, M. Lebwohl Grant/research support from: Janssen Research & Development, LLC, P. Szapary Employee of: Janssen Research & Development, LLC, Y. Wasfi Employee of: Janssen Research & Development, LLC, D. Chan Employee of: Janssen Research & Development, LLC, Y. Shen Employee of: Janssen Research & Development, LLC, V. Ho Grant/research support from: Janssen Research & Development, LLC, P. Ghislain Grant/research support from: Janssen Research & Development, LLC, B. Strober Grant/research support from: Janssen Research & Development, LLC, K. Reich Grant/research support from: Janssen Research & Development, LLC
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