Nail Psoriasis and Biologics

2009 ◽  
Vol 13 (1) ◽  
pp. 1-5 ◽  
Author(s):  
Kristin Noiles ◽  
Ronald Vender
Keyword(s):  
Clinical Trials ◽  
Literature Review ◽  
Severity Index ◽  
Phase Iii ◽  
Controlled Study ◽  
Extensive Literature ◽  
Open Label ◽  
Double Blind ◽  
Nail Psoriasis ◽  
Percent Improvement

Background: Since the advent of biologic therapies for psoriasis, reports of efficacy in nail psoriasis have appeared in the literature and at international conferences with increasing frequency. Objective: This article aims to review the existing literature on the use of biologics in the treatment of nail psoriasis. Methods: An extensive literature review was conducted using OVID Medline. Studies examining the efficacy of biologics in the treatment of nail psoriasis were documented. Results: A literature review revealed few clinical trials specifically concentrating on nail psoriasis; however, nails have been assessed in larger clinical trials for cutaneous psoriasis. A large, multicenter, phase III, double-blind, placebo-controlled study of infliximab administered as a brief induction regimen at weeks 0, 2, and 6 followed by a single infusion every 8 weeks revealed statistically significant mean percent improvement in the Nail Psoriasis Severity Index (NAPSI) score over placebo at both week 10 (26.8% vs −7.7%, respectively; p < .001) and week 24 (57.2% vs −4.1%, respectively; p < .001). For other biologics, evidence has thus far been largely anecdotal, appearing as either case studies or extracted secondarily from open-label prospective trials in plaque psoriasis or psoriatic arthritis. Conclusion: Infliximab appears to be the most effective treatment for nail psoriasis to date.

The premonitory phase of migraine and migraine management

Cephalalgia ◽  
2012 ◽  
Vol 33 (13) ◽  
pp. 1117-1121 ◽  
Author(s):  
Werner J Becker
Keyword(s):  
Literature Review ◽  
Migraine Attack ◽  
Management Strategy ◽  
Controlled Study ◽  
Open Label ◽  
Double Blind ◽  
Open Label Study ◽  
Label Study ◽  
Medication Treatment ◽  
Premonitory Symptoms

Objective: The objective was to determine, through a literature review, whether treatment during the premonitory phase of migraine is a potentially useful migraine management strategy. Methods: A general literature review was done with regard to the nature of migraine premonitory symptoms, their frequency, their reliability in predicting migraine attacks, and the effectiveness of medication treatment when given during the premonitory phase. Results: Many different symptoms have been reported as premonitory symptoms that occur before migraine attacks. Up to 87% of patients with migraine may experience premonitory symptoms, although some studies have provided estimates as low as 33%. In selected patients, premonitory symptoms may be relatively reliable predictors of a migraine attack to follow. Both naratriptan (open-label study) and domperidone (double-blind, randomized, placebo-controlled study) have been reported to be effective when given during the premonitory phase. Conclusions: More research is needed, but there is some evidence that medication treatment during the premonitory phase has the potential to be helpful in selected patients with migraine.

XP-828L in the Treatment of Mild to Moderate Psoriasis: Randomized, Double-Blind, Placebo-Controlled Study

2006 ◽  
Vol 10 (5) ◽  
pp. 241-248 ◽  
Author(s):  
Yves Poulin ◽  
Robert Bissonnette ◽  
Christina Juneau ◽  
Kim Cantin ◽  
Rejean Drouin ◽  
...  
Keyword(s):  
Severity Index ◽  
Controlled Study ◽  
Open Label ◽  
Double Blind ◽  
Open Label Study ◽  
Double Blind Placebo ◽  
Sweet Whey ◽  
Severity Index Score ◽  
Group A ◽  
Group B

Background: XP-828L, a protein extract obtained from sweet whey, has demonstrated potential benefit for the treatment of mild to moderate psoriasis in an open-label study. Objective: To study in a randomized, double-blind, placebo-controlled study the safety and efficacy of XP-828L in the treatment of mild to moderate psoriasis. Design: XP-828L 5 g/d (group A, n = 42) or placebo (group B, n = 42) was given orally for 56 days followed by XP-828L 5 g/d in group A and by XP-828L 10 g/d in group B for an additional 56 days. Results: Patients receiving XP-828L 5 g/d for 56 days had an improved Physician's Global Assessment (PGA) score compared with patients under placebo ( p < .05). Considering the data of group A only, the PGA score improved from day 1 to day 56 ( p < .01); the Psoriasis Area and Severity Index score improved as well, but to a lesser extent ( p < .05). Conclusion: Oral administration of 5 g/d XP-828L compared with a placebo significantly improved the PGA score of patients with mild to moderate psoriasis.

KEYNOTE-355: Randomized, double-blind, phase III study of pembrolizumab (pembro) + chemotherapy (chemo) vs placebo (PBO) + chemo for previously untreated, locally recurrent, inoperable or metastatic triple-negative breast cancer (mTNBC).

2018 ◽  
Vol 36 (5_suppl) ◽  
pp. TPS18-TPS18 ◽  
Author(s):  
Javier Cortés ◽  
Zifang Guo ◽  
Vassiliki Karantza ◽  
Gursel Aktan
Keyword(s):  
Antitumor Activity ◽  
Disease Recurrence ◽  
Phase Iii ◽  
Controlled Study ◽  
Adjuvant Setting ◽  
Open Label ◽  
Double Blind ◽  
End Points ◽  
Phase Iii Study ◽  
Locally Recurrent

TPS18 Background: In the phase Ib KEYNOTE-012 study, the anti–PD-1 antibody pembro demonstrated promising antitumor activity and acceptable safety as monotherapy in pretreated patients (pts) with PD-L1+ mTNBC. Adding pembro to chemo may enhance antitumor activity. KEYNOTE-355 (NCT02819518) is a global phase III study of pembro+chemo vs PBO+chemo in pts with previously untreated, locally recurrent, inoperable TNBC/mTNBC. Methods: Eligible pts are ≥18 y and have centrally confirmed, locally recurrent, inoperable TNBC or mTNBC not previously treated with chemo (prior chemo in [neo]adjuvant setting is allowed); measurable disease per RECIST v1.1; ECOG PS 0-1; ≥6 mo between definitive surgery or last dose of adjuvant chemo, whichever was last; and first disease recurrence (≥12 mo if prior treatment with same-class agent). Part 1 is an open-label, unblinded safety run-in of ~30 pts in 3 arms (pembro+nab-paclitaxel, pembro+paclitaxel, pembro+gemcitabine/carboplatin). Part 2 is a double-blind, PBO-controlled study of ~828 pts randomized 2:1 to pembro 200 mg every 3 weeks + chemo (nab-paclitaxel 100 mg/m2 on d 1, 8, and 15 every 28 d; paclitaxel 90 mg/m2 on d 1, 8, and 15 every 28 d; or gemcitabine 1000 mg/m2+ carboplatin AUC 2 on d 1 and 8 every 21 d) or PBO+chemo. Crossover is not allowed. Stratification factors are study chemo (taxane vs gemcitabine/carboplatin), tumor PD-L1 expression (+/-), and prior therapy with same-class agent in the (neo)adjuvant setting (yes/no). Treatment will occur for ≤35 administrations (pembro/PBO only) or until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or decision to discontinue. Primary end points are safety in part 1 and PFS (by RECIST v1.1, central radiology review) and OS in part 2; secondary end points include ORR (by RECIST v1.1, central radiology review) and duration of response. AEs will be graded per NCI CTCAE v4.0. Response will be assessed at wk 8, 16, 24, then at 9-wk intervals up to 1 y, and at 12-wk intervals thereafter. Interim safety analysis will occur after pts complete 1 treatment cycle in part 1. Clinical trial information: NCT02819518.

Nagelpsoriasis: Anti-IL17-Therapie ist erfolgversprechend

2020 ◽  
Vol 8 (3) ◽  
pp. 111-113
Author(s):  
Sandra Philipp
Keyword(s):  
Quality Of Life ◽  
Severity Index ◽  
Primary Objective ◽  
Controlled Study ◽  
Upper Respiratory Tract ◽  
Double Blind ◽  
Nail Psoriasis ◽  
Patient Questionnaires ◽  
Tract Infections

Background: Nail psoriasis is associated with functional impairment, pain and reduced quality of life. Objectives: To demonstrate the superiority of secukinumab over placebo in clearing nail psoriasis as assessed by the Nail Psoriasis Severity Index (NAPSI) at week 16 and over time up to week 132. Presented here is the week 32 interim analysis. Impact on quality of life was assessed by Nail Assessment in Psoriasis and Psoriatic Arthritis (NAPPA) patient questionnaires. Methods: TRANSFIGURE is a double-blind, randomized, placebo-controlled study in patients with moderate-to-severe plaque and nail psoriasis. Results: The primary objective of this study was met: both doses of secukinumab were superior to placebo at week 16 (NAPSI improvements of -45,3%, -37,9% and -10,8% for secukinumab 300 mg and 150 mg and placebo, respectively, P<0,001). Significant improvements were seen in patients’ quality of life: the NAPPA-Quality of Life total score median decreases at week 16 were 60,9%, 49,9% and 15,8% for secukinumab 300 mg and 150 mg and placebo, respectively (P < 0_001). Improvement in nail psoriasis continued to week 32: NAPSI percentage change reached -63,2% and -52,6% for secukinumab 300 mg and 150 mg, respectively. Skin clearance measured by ≥90% improvement in Psoriasis. Area and Severity Index was significant (rates of 72,5%, 54,0% and 1,7% for secukinumab 300mg and 150mg and placebo at week 16, respectively, P<0,001) and was sustained to week 32. The most common adverse events were nasopharyngitis, headache and upper respiratory tract infections. Conclusion: Secukinumab demonstrated significant and clinically meaningful efficacy and quality-of-life improvements for patients with nail psoriasis up to week 32.

scholarly journals P131 Efficacy and safety of olokizumab in a phase III trial of patients with moderately to severely active RA inadequately controlled by methotrexate: placebo and active controlled study

Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_1) ◽  
Author(s):  
Eugen Feist ◽  
Saima Chohan ◽  
Saeed Fatenejad ◽  
Sergey Grishin ◽  
Elena Korneva ◽  
...  
Keyword(s):  
Adverse Events ◽  
Randomised Clinical Trial ◽  
Phase Iii ◽  
Controlled Study ◽  
Open Label ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Acr20 Response ◽  
Phase Iii Trial ◽  
Secondary Endpoints

Abstract Background/Aims  Olokizumab (OKZ) is a new humanised monoclonal antibody targeting IL-6 directly. Here we present the results of a global randomised clinical trial (RCT) in patients (pts) with RA. Methods  This double-blind, placebo (PBO) and active controlled, RCT in pts with moderately to severely active RA despite MTX (ClinicalTrials.gov Identifier NCT02760407, CREDO2) was carried out in 18 counties. Pts were randomized 2:2:2:1 to receive subcutaneous injections of OKZ 64 mg every 2 weeks (q2w), OKZ 64 mg once every 4 weeks (q4w), adalimumab (ADA) 40mg q2w or PBO for 24 weeks, plus MTX. After week 24, subjects either rolled over into an open-label study or entered the Safety Follow-Up Period for another 20 weeks. The primary endpoint was ACR 20% (ACR20) response rate at week 12. Secondary endpoints included: percentage of subjects with DAS28-CRP &lt;3.2 and improvement of HAQ-DI from baseline at week 12, ACR50 and percentage of subjects with remission (CDAI) ≤2.8 at week 24. Safety outcomes, including adverse events, serious adverse events and laboratory abnormalities were assessed. Results  1,648 subjects were randomised to OKZ 64mg q2w (n = 464), OKZ 64mg q4w (n = 479), ADA 40mg (n = 462) or PBO (n = 243). Baseline characteristics were comparable across treatment arms. The vast majority of the pts completed 24 weeks treatment period 421 (90.7%) in q2w, 437 (91.2%) in q4w, 413 (89.4%) in ADA and 208 (85.6%) in PBO arms and enrolled to open-label extension study: 410 (88.4%), 422 (88.1%), 397 (85.9%) and 199 (81.9%) pts, respectively. Both regimens of OKZ were significantly better than PBO in all primary and secondary endpoints. Furthermore, non-inferiority to ADA was demonstrated for the pre-defined endpoints of ACR20 and DAS28-CRP&lt;3.2 for both OKZ treatment groups. The efficacy outcomes were maintained throughout the 24-week period of the study. Overall incidence of treatment-emergent adverse events (TEAEs) was 70.0% in OKZ q2w arm; 70.9% in OKZ q4w arm, 65.4% in ADA arm and 63.4% in PBO, TEAEs leading to study treatment discontinuation were reported in 4.5%, 6.3%, 5.6% and 3.7% pts, respectively. The number of deaths were comparable among arms: 3 (0.6%; 2 infections, 1 cerebrovascular accident) in the OKZ q2w arm, 2 (0.4%; 1 infection, 1 myocardial ischemia) in OKZ q4w arm, 1 (0.2%; infection) in ADA arm and 1 (0.4%; sudden death) in PBO. The most common treatment-emergent serious adverse events (TESAEs) were infections. Conclusion  In this global Phase III trial, treatment with OKZ plus MTX in both regimes (OKZ 64 mg q2w and OKZ 64 mg q4w) was associated with significant improvements in the signs, symptoms and physical function of RA compared to PBO plus MTX and non-inferior to ADA plus MTX over a 24-week period. OKZ was well tolerated and no new safety signals were observed. Disclosure  E. Feist: Consultancies; R-Pharm, Abbvie, BMS, Celgene, Janssen, Lilly, Medac, MSD, Novartis, Pfizer, Roche/Chugai, Sanofi. Honoraria; R-Pharm, Abbvie, AB2Bio, BMS, Celgene, Janssen, Lilly, Medac, MSD, Novartis, Pfizer, Roche/Chugai, Sanofi, Sobi, UCB. Member of speakers’ bureau; R-Pharm, Abbvie, AB2Bio, BMS, Celgene, Janssen, Lilly, Medac, MSD, Novartis, Pfizer, Roche/Chugai, Sanofi, Sobi, UCB. Grants/research support; Lilly, Novartis, Pfizer, Roche/Chugai. S. Chohan: None. S. Fatenejad: Consultancies; RPharm International. Shareholder/stock ownership; Pfizer. S. Grishin: Corporate appointments; Employed by R-Pharm. E. Korneva: Corporate appointments; Employed by R-Pharm. E.L. Nasonov: Honoraria; Lilly, Abbnie, Prizer, Biocad, R-Pharm. Member of speakers’ bureau; Lilly, Abbnie, Prizer, Biocad, R-Pharm. A. Rowińska-Osuch: Consultancies; R-Pharm. M. Samsonov: Corporate appointments; Employed by R-Pharm.

Randomized Phase III and Extension Studies of Naldemedine in Patients With Opioid-Induced Constipation and Cancer

2017 ◽  
Vol 35 (34) ◽  
pp. 3859-3866 ◽  
Author(s):  
Nobuyuki Katakami ◽  
Toshiyuki Harada ◽  
Toru Murata ◽  
Katsunori Shinozaki ◽  
Masakazu Tsutsumi ◽  
...  
Keyword(s):  
Phase Iii ◽  
Controlled Study ◽  
Open Label ◽  
Double Blind ◽  
Once Daily ◽  
Spontaneous Bowel Movement ◽  
Patients With Cancer ◽  
End Point ◽  
Μ Opioid Receptor ◽  
To Receive

Purpose Opioid-induced constipation (OIC) is a frequent and debilitating adverse effect (AE) of opioids—common analgesics for cancer pain. We investigated the efficacy and safety of a peripherally acting μ-opioid receptor antagonist, naldemedine (S-297995), for OIC, specifically in patients with cancer. Patients and Methods This phase III trial consisted of a 2-week, randomized, double-blind, placebo-controlled study (COMPOSE-4) and an open-label, 12-week extension study (COMPOSE-5). In COMPOSE-4, eligible adults with OIC and cancer were randomly assigned on a 1:1 basis to receive once-daily oral naldemedine 0.2 mg or placebo. The primary end point was the proportion of spontaneous bowel movement (SBM) responders (≥ 3 SBMs/week and an increase of ≥ 1 SBM/week from baseline). The primary end point of COMPOSE-5 was safety. Results In COMPOSE-4, 193 eligible patients were randomly assigned to naldemedine (n = 97) or placebo (n = 96). The proportion of SBM responders in COMPOSE-4 was significantly greater with naldemedine than with placebo (71.1% [69 of 97 patients] v 34.4% [33 of 96 patients]; P < .0001). A greater change from baseline was observed with naldemedine than with placebo in the frequency of SBMs/week (5.16 v 1.54; P < .0001), SBMs with complete bowel evacuation/week (2.76 v 0.71; P < .0001), and SBMs without straining/week (3.85 v 1.17; P = .0005). In COMPOSE-4, more patients treated with naldemedine than with placebo reported treatment-emergent AEs (TEAEs) (44.3% [43 of 97 patients] v 26.0% [25 of 96 patients]; P = .01); in COMPOSE-5, 105 (80.2%) of 131 of patients reported TEAEs. Diarrhea was the most frequently reported TEAE in COMPOSE-4 (19.6% [19 of 97 patients] v 7.3% [seven of 96 patients] with naldemedine v placebo) and COMPOSE-5 (18.3% [24 of 131 patients] with naldemedine). Naldemedine was not associated with signs or symptoms of opioid withdrawal and had no notable impact on opioid-mediated analgesia. Conclusion Once-daily oral naldemedine 0.2 mg effectively treated OIC and was generally well tolerated in patients with OIC and cancer.

scholarly journals Clinical staging in amyotrophic lateral sclerosis: analysis of Edaravone Study 19

2020 ◽  
pp. jnnp-2020-323271
Author(s):  
Ammar Al-Chalabi ◽  
Adriano Chiò ◽  
Charlotte Merrill ◽  
Gerry Oster ◽  
Rebecca Bornheimer ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Amyotrophic Lateral Sclerosis ◽  
Phase Iii ◽  
Clinical Staging ◽  
Rapid Progression ◽  
Open Label ◽  
Double Blind ◽  
End Points ◽  
Staging Systems ◽  
Lateral Sclerosis

ObjectiveThis was a post hoc analysis of the Edaravone Phase III Study MCI186-19 (‘Study 19’) to examine the utility of clinical staging systems as end points in clinical trials in amyotrophic lateral sclerosis (ALS).MethodsAmyotrophic Lateral Sclerosis Functional Rating Scale—Revised item scores from Study 19 were retrospectively mapped to King’s stage and Milano-Torino staging (MiToS) stage. We assessed the percentage of patients who experienced progression in King’s and MiToS stages during Study 19. We also assessed disease progression in subgroups of patients according to baseline King’s stage.ResultsDuring double-blind treatment, the percentage of patients who experienced a progression in King’s stage was lower for edaravone (42.0%, 95% CI 30.4% to 53.6%) than placebo (55.9%, 95% CI 44.1% to 67.6%). The most pronounced effect was noted among patients who were in stage 1 and was maintained throughout open-label treatment. An analysis of a ≥2-stage progression in MiToS stage showed no difference between treatment arms during double-blind treatment, but during the open-label period, more rapid progression was noted among patients in the placebo–edaravone arm than among those in the edaravone–edaravone arm (log-rank test, p<0.001).ConclusionsThe King’s and MiToS staging systems provided utility in assessing clinical progression in Edaravone Study 19. These findings may support the use of staging systems as end points in ALS clinical trials and to understand the timing of benefit as measured by these scales.

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