scholarly journals HiSCR (Hidradenitis Suppurativa Clinical Response): a novel clinical endpoint to evaluate therapeutic outcomes in patients with hidradenitis suppurativa from the placebo‐controlled portion of a phase 2 adalimumab study

2015 ◽  
Vol 30 (6) ◽  
pp. 989-994 ◽  
Author(s):  
A.B. Kimball ◽  
J.M. Sobell ◽  
C.C. Zouboulis ◽  
Y. Gu ◽  
D.A. Williams ◽  
...  
Keyword(s):  
Clinical Response ◽  
Hidradenitis Suppurativa ◽  
Phase 2 ◽  
Clinical Endpoint ◽  
Therapeutic Outcomes

Staphylococcus aureus Carriage in Hidradenitis Suppurativa: Impact on Response to Adalimumab

Dermatology ◽  
2021 ◽  
pp. 1-6
Author(s):  
Dimitra Stergianou ◽  
Vassiliki Tzanetakou ◽  
Maria Argyropoulou ◽  
Theodora Kanni ◽  
Pantelis G. Bagos ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Clinical Response ◽  
Odds Ratio ◽  
Hidradenitis Suppurativa ◽  
Positive Culture ◽  
Nasal Carriage ◽  
Loss Of Response ◽  
Response Score ◽  
Stimulation Of

<b><i>Background:</i></b> Several patients with hidradenitis suppurativa (HS) present flare-ups during treatment with adalimumab (ADA), the cause of which is not clear. ADA is the only FDA-approved biologic for the therapy of moderate-to-severe HS. A previous study of our group has shown that <i>Staphylococcus aureus</i> stimulation of whole blood affects the production of human β-defensin 2 and modulates HS severity. It is, therefore, hypothesized, that carriage of <i>S. aureus</i> may drive HS flare-ups. <b><i>Objective:</i></b> To explore the association between carriage of <i>S. aureus</i> and loss of response to ADA. <b><i>Patients and Methods:</i></b> Among patients with moderate-to-severe HS without carriage of <i>S. aureus</i> at start of treatment with ADA, we investigated for carriage of <i>S. aureus</i> from the nares when flare-ups occurred. Flare-ups were pre-defined as at least 25% increase of inflammatory lesions (sum of inflammatory nodules and abscesses) from baseline. Samplings were also done after completion of 12 weeks of ADA treatment from all patients who did not present flare-ups. Clinical response to ADA was assessed by the HS Clinical Response score (HiSCR). <b><i>Results:</i></b> Thirty-nine patients were studied; 24 with Hurley II stage HS and 15 with Hurley III stage HS. Twenty-nine patients achieved HiSCR after 12 weeks of treatment without any flare-ups; 10 patients had flare-ups and failed HiSCR. Three (10.3%) and 5 (50%) patients, respectively, had nasal carriage of <i>S. aureus</i> (odds ratio 8.67; 95% CI 1.54–48.49; <i>p</i> = 0.014). Among 32 patients reaching follow-up week 48, 20 patients achieved HiSCR and 12 had flare-ups leading to ADA failure; 2 (10%) and 5 (41.7%) patients, respectively, had positive culture for <i>S. aureus</i> (odds ratio 6.42; 95% CI 1.00–41.20; <i>p</i> = 0.05). <b><i>Conclusion:</i></b> Nasal carriage of <i>S. aureus</i> may be associated with loss of response to ADA. Findings need confirmation in larger series of patients.

Systemic antitumor effect and clinical response in a phase 2 trial of intratumoral electroporation of plasmid interleukin-12 in patients with advanced melanoma.

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. 9025-9025 ◽  
Author(s):  
Adil Daud ◽  
Alain Patrick Algazi ◽  
Michelle T. Ashworth ◽  
Lawrence Fong ◽  
Jera Lewis ◽  
...  
Keyword(s):  
Clinical Response ◽  
Antitumor Effect ◽  
Advanced Melanoma ◽  
Interleukin 12 ◽  
Phase 2 ◽  
Phase 2 Trial

scholarly journals Multicenter, Double-Blind, Randomized, Phase 2 Study Evaluating the Novel Antibiotic Cadazolid in Patients with Clostridium difficile Infection

2015 ◽  
Vol 59 (10) ◽  
pp. 6266-6273 ◽  
Author(s):  
Thomas Louie ◽  
Carl Erik Nord ◽  
George H. Talbot ◽  
Mark Wilcox ◽  
Dale N. Gerding ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
Clinical Response ◽  
Recurrence Rate ◽  
Primary Endpoint ◽  
Clinical Cure ◽  
The United States ◽  
Phase 2 ◽  
Double Blind ◽  
Content Type ◽  
Phase 2 Study

ABSTRACTCadazolid, a novel fluoroquinolone-oxazolidinone antibiotic, exhibits potentin vitroactivity againstClostridium difficile, including the epidemic BI/NAP1/027 strain. This multicenter, randomized, double-blind, active reference group, phase 2 study evaluated the efficacy and safety of oral cadazolid in treatment of adult patients withC. difficileinfection (CDI). Eligible patients with first occurrence/first recurrence of CDI were randomized 1:1:1:1 to 250, 500, or 1,000 mg cadazolid twice daily (BID) or oral 125 mg vancomycin four times daily (QID) for 10 days. The primary endpoint was clinical cure at test of cure (48 ± 24 h after the end of treatment; modified intent-to-treat population), defined as resolution of diarrhea with no further CDI treatment required. Secondary endpoints included recurrence rate, sustained clinical response (clinical cure without recurrence), and time to diarrhea resolution. Of 84 patients enrolled, 20, 22, 20, and 22 received 250, 500, or 1,000 mg cadazolid BID or 125 mg vancomycin QID, respectively. The primary endpoint was achieved in 76.5% (80% confidence interval [CI], 58.4, 89.3), 80.0% (63.9, 91.0), 68.4% (51.1, 82.5), and 68.2% (52.3, 81.3) of patients, respectively. There was no evidence of a cadazolid dosage-dependent response. Each dosage of cadazolid resulted in a lower recurrence rate than with vancomycin (18.2 to 25.0% versus 50%). Consequently, higher sustained clinical response rates were observed with cadazolid (46.7 to 60.0%) than with vancomycin (33.3%). The times to diarrhea resolution were similar for cadazolid and vancomycin. Cadazolid was well tolerated, with no safety signal observed. The results of this phase 2 study support further clinical development of cadazolid. (This study has been registered in the United States at ClinicalTrials.gov under registration no. NCT01222702 and in Europe with the European Medicines Agency under registration no. EUDRA-CT 2010-020941-29.)

scholarly journals A phase 2 study of the farnesyltransferase inhibitor tipifarnib in poor-risk and elderly patients with previously untreated acute myelogenous leukemia

Blood ◽  
2006 ◽  
Vol 109 (4) ◽  
pp. 1387-1394 ◽  
Author(s):  
Jeffrey E. Lancet ◽  
Ivana Gojo ◽  
Jason Gotlib ◽  
Eric J. Feldman ◽  
Jacqueline Greer ◽  
...  
Keyword(s):  
Older Adults ◽  
Clinical Response ◽  
Acute Myelogenous Leukemia ◽  
Myelogenous Leukemia ◽  
Poor Performance Status ◽  
Phase 2 ◽  
Farnesyltransferase Inhibitor ◽  
Poor Risk ◽  
Phase 2 Study ◽  
Acute Myelogenous

Abstract Outcomes for older adults with acute myelogenous leukemia (AML) are poor due to both disease and host-related factors. In this phase 2 study, we tested the oral farnesyltransferase inhibitor tipifarnib in 158 older adults with previously untreated, poor-risk AML. The median age was 74 years, and a majority of patients had antecedent myelodysplastic syndrome. Complete remission (CR) was achieved in 22 patients (14%); partial remission or hematologic improvement occurred in 15 patients, for an overall response rate of 23%. The median duration of CR was 7.3 months and the median survival of complete responders was 18 months. Adverse karyotype, age 75 years or older, and poor performance status correlated negatively with survival. Early death in the absence of progressive disease was rare, and drug-related nonhematologic serious adverse events were observed in 74 patients (47%). Inhibition of farnesylation of the surrogate protein HDJ-2 occurred in the large majority of marrow samples tested. Baseline levels of phosphorylated mitogen-activated protein kinase and AKT did not correlate with clinical response. Tipifarnib is active and well tolerated in older adults with poor-risk AML and may impart a survival advantage in those patients who experience a clinical response.

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