scholarly journals Efficacy of tofacitinib in reduction of inflammation detected on MRI in patients with Psoriatic ArthritiS presenTing with axial involvement (PASTOR): protocol of a randomised, double-blind, placebo-controlled, multicentre trial

BMJ Open ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. e048647
Author(s):  
Fabian Proft ◽  
Murat Torgutalp ◽  
Burkhard Muche ◽  
Valeria Rios Rodriguez ◽  
Maryna Verba ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Treatment Period ◽  
Group Treatment ◽  
Activity Index ◽  
Treatment Options ◽  
Study Endpoint ◽  
Primary Study ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Axial Involvement

IntroductionPsoriatic arthritis (PsA) is an inflammatory disease characterised by synovitis, enthesitis, dactylitis and axial involvement. The prevalence of axial involvement ranges from 25% to 70% in this patient group. Treatment recommendations for axial PsA were mainly extrapolated from guidelines for axial spondyloarthritis, and the main treatment options are non-steroidal anti-inflammatory drugs and biological disease-modifying antirheumatic drugs (tumour necrosis factor, IL-17 and IL-23 inhibitors). Tofacitinib was approved for the treatment of PsA and its efficacy on axial inflammation has been demonstrated in a phase II study of ankylosing spondylitis (AS). This prospective study aims to evaluate the efficacy of tofacitinib in reducing inflammation in the sacroiliac joints (SIJs) and spine on MRI in patients with axial disease of their PsA presenting with active axial involvement compatible with axial PsA.Methods and analysesThis is a randomised, double-blind, placebo-controlled, multicentre clinical trial in patients with axial PsA who have evidence of axial involvement, active disease as defined by a Bath AS Disease Activity Index score of ≥4 and active inflammation on MRI of the SIJs and/or spine as assessed by and independent central reader. The study includes a 6-week screening period, a 24-week treatment period, which consist of a 12-week placebo-controlled double-blind treatment period followed by a 12-week active treatment period with tofacitinib for all participants, and a safety follow-up period of 4 weeks. At baseline, 80 subjects shall be randomised (1:1) to receive either tofacitinib or matching placebo for a 12-week double-blind treatment period. At week 12, an MRI of the whole spine and SIJs will be performed to evaluate the primary study endpoint.Ethics and disseminationThe study will be performed according to the ethical principles of the Declaration of Helsinki and the German drug law. The independent ethics committees of each centre approved the ethical, scientific and medical appropriateness of the study before it was conducted.Trial registration numberNCT04062695; ClinicalTrials.gov and EudraCT No: 2018-004254-22; European Union Clinical Trials Register.

scholarly journals POS0198 EFFICACY AND SAFETY OF DEUCRAVACITINIB, AN ORAL, SELECTIVE TYROSINE KINASE 2 INHIBITOR, IN PATIENTS WITH ACTIVE PSORIATIC ARTHRITIS: RESULTS FROM A PHASE 2, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 314.2-315
Author(s):  
P. J. Mease ◽  
A. Deodhar ◽  
D. Van der Heijde ◽  
F. Behrens ◽  
A. Kivitz ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Tyrosine Kinase ◽  
Phase 2 ◽  
Efficacy And Safety ◽  
Research Support ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Phase 2 Trial ◽  
Tyrosine Kinase 2 ◽  
Sf 36

Background:Tyrosine kinase 2 (TYK2) is an intracellular kinase that mediates signaling by key cytokines involved in psoriatic arthritis (PsA) and plaque psoriasis (PsO) pathogenesis. Deucravacitinib is a novel oral agent that selectively inhibits TYK2 via an allosteric mechanism by binding to the nonconserved regulatory domain of the kinase. A previous Phase 2 trial in PsO had demonstrated that deucravacitinib was efficacious and well tolerated, with no laboratory abnormalities observed.Objectives:To evaluate the efficacy and safety of deucravacitinib in active PsA.Methods:This is an ongoing, 1-year, randomized, double-blind, placebo (PBO)-controlled (initial 16 weeks), multiregional, Phase 2 trial (NCT03881059). Eligible patients had a PsA diagnosis for ≥6 months, met CASPAR criteria, and had active disease with ≥3 tender and ≥3 swollen joints, C-reactive protein ≥3 mg/L (ULN, 5 mg/L), and ≥1 psoriatic lesion (≥2 cm). Patients had failed or were intolerant to ≥1 nonsteroidal anti-inflammatory drug, corticosteroid, conventional synthetic disease-modifying antirheumatic drug (csDMARD), and/or 1 TNF inhibitor (TNFi; ≤30%). Patients were randomized 1:1:1 to deucravacitinib 6 mg once daily (QD) or 12 mg QD, or PBO. The primary endpoint was achievement of ACR 20 response at Week 16. Additional endpoints included the proportion of patients achieving ACR 50/70 response, Health Assessment Questionnaire-Disability Index (HAQ-DI) response (≥0.35 improvement from baseline), enthesitis resolution (Leeds Index score of 0), minimal disease activity, change from baseline in SF-36 physical component score (SF-36 PCS) and mental component score (SF-36 MCS), Psoriasis Area and Severity Index (PASI) 75 response, adverse events (AEs), and laboratory parameters.Results:Of 203 patients randomized, 180 (89%) completed 16 weeks of treatment (deucravacitinib 6 mg QD, 63/70 [90%]; deucravacitinib 12 mg QD, 59/67 [88%]; PBO, 58/66 [88%]). Demographic and baseline disease characteristics were similar across groups. Mean age was 49.8 years, 51% of patients were female, median PsA duration was 4.5 years, 66% of patients used csDMARDs at baseline and throughout the study, and 15% had used a TNFi. This study met its primary endpoint, with deucravacitinib 6 mg and 12 mg QD demonstrating significantly higher ACR 20 responses versus PBO at Week 16 (Figure 1). Additional endpoints were also met with deucravacitinib versus PBO (Figure 1). Adjusted mean changes from baseline in SF-36 PCS and SF-36 MCS at Week 16, respectively, were significantly higher in the deucravacitinib 6 mg QD group (5.6 vs 2.3, P=0.0062; 3.6 vs 0.7, P=0.0211) and 12 mg QD group (5.8 vs 2.3, P=0.0042; 3.5 vs 0.7, P=0.0263) compared with PBO. PASI 75 responses were also significantly higher in the deucravacitinib groups (P≤0.0136 vs PBO). The most common AEs in the deucravacitinib 6 mg/12 mg/PBO groups, respectively, during the 16-week treatment period were nasopharyngitis (5.7%/17.9%/7.6%), sinusitis (0%/7.5%/0%), headache (7.1%/1.5%/4.5%), and rash (4.3%/6.0%/0%). No serious AEs, herpes zoster infections, opportunistic infections, or thrombotic events were reported in deucravacitinib-treated patients during this period. Additionally, no significant changes from baseline in hematologic parameters (lymphocytes, neutrophils, platelets, and hemoglobin) or serum lipids were observed with deucravacitinib treatment.Conclusion:Deucravacitinib was efficacious versus PBO over 16 weeks in patients with active PsA. Treatment was generally well tolerated and the safety and laboratory parameter profile of deucravacitinib was consistent with that observed in an earlier Phase 2 PsO trial.Acknowledgements:This study was sponsored by Bristol Myers Squibb. Professional medical writing assistance was provided by Peloton Advantage, LLC, an OPEN Health company, and funded by Bristol Myers Squibb.Disclosure of Interests:Philip J Mease Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, SUN Pharma, UCB, Grant/research support from: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, SUN Pharma, UCB, Atul Deodhar Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, Glaxo Smith & Kline, Janssen, Novartis, Pfizer, UCB, Grant/research support from: AbbVie, Eli Lilly, Glaxo Smith & Kline, Novartis, Pfizer, UCB, Désirée van der Heijde Consultant of: AbbVie, Amgen, Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB Pharma, Frank Behrens Consultant of: Pfizer, AbbVie, Sanofi, Lilly, Novartis, Genzyme, Boehringer, Janssen, MSD, Celgene, Roche, Chugai, Bristol Myers Squibb, UCB Pharma, Grant/research support from: Pfizer, Janssen, Chugai, Celgene, Roche, Alan Kivitz Shareholder of: Pfizer, Sanofi, GlaxoSmithKline, Gilead Sciences, Inc., Novartis, Paid Consultant: AbbVie, Boehringer Ingelheim, Flexion, Janssen, Pfizer, Sanofi, Regeneron, SUN Pharma Advanced Research, Gilead Sciences, Inc., Speakers bureau: Celgene, Merck, Lilly, Novartis, Pfizer, Sanofi, Genzyme, Flexion, AbbVie, Jonghyeon Kim Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Shalabh Singhal Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Miroslawa Nowak Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Subhashis Banerjee Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb

Simethicone in the Treatment of Infant Colic: A Randomized, Placebo-Controlled, Multicenter Trial

PEDIATRICS ◽  
1994 ◽  
Vol 94 (1) ◽  
pp. 29-34
Author(s):  
Thomas J. Metcalf ◽  
Thomas G. Irons ◽  
Lawrence D. Sher ◽  
Paul C. Young
Keyword(s):  
Treatment Period ◽  
Multicenter Trial ◽  
Crossover Fashion ◽  
Infantile Colic ◽  
Parental Report ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Infant Colic ◽  
Geographic Regions

Objective. To determine the efficacy of simethicone in the treatment of infant colic. Design. Randomized, double blind, placebo-controlled. Setting. Three general pediatric practices in distinct geographic regions. Patients. Eighty-three infants between 2 and 8 weeks of age with infant colic. Interventions. Treatment with simethicone and placebo in double blind crossover fashion. Results. A total of 166 treatment periods, ranging from 3 to 10 days, were evaluated in the 83 infants. Compared to baseline, improvement in symptoms was reported for 54% of the treatment periods, worsening was reported for 22%, and, for 24%, there was no change. The likelihood of the treatment period being rated as showing improvement, worsening, or no change was the same whether the infant was receiving placebo or simethicone. Twenty-eight percent of he infants responded only to simethicone, 37% only to placebo, and 20% responded to both. No statistically significant differences were noted among these three groups of responders. No difference could be shown even when infants with "gas-related symptoms" (by parental report) were separated out as a group. Conclusion. Although both produced perceived improvements in symptoms, simethicone is no more effective than placebo in the treatment of infantile colic.

FRI0362 COMPARATIVE EFFECTIVENESS OF USTEKINUMAB (UST) AND TNF INHIBITORS (TNFI) IN PATIENTS WITH PSORIATIC ARTHRITIS (PSA) IN THE REAL-WORLD, MULTINATIONAL PSABIO STUDY: 12-MONTH FOLLOW-UP

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 778-779
Author(s):  
J. S. Smolen ◽  
S. Siebert ◽  
T. Korotaeva ◽  
P. Bergmans ◽  
K. De Vlam ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Disease Activity ◽  
Real World ◽  
Activity Index ◽  
Treatment Options ◽  
Disease Activity Index ◽  
Rapid Screening ◽  
Research Support ◽  
Real World Data

Background:Among treatment options for PsA, IL-12/23 inhibition with UST was the first new biologic mode of action after TNFi. Few real-world data comparing UST with TNFi are available.Objectives:Comparison of UST and TNFi treatment effectiveness within the prospectively followed PsABio cohort at 12-month (mo) follow-up.Methods:The PsABio study (NCT02627768) evaluates effectiveness, tolerability and persistence of 1st, 2nd or 3rd-line UST or TNFi in PsA. Proportions of patients (pts) reaching MDA/very low disease activity (VLDA) and clinical Disease Activity index for PSoriatic Arthritis (cDAPSA) LDA/remission are described. Comparison across UST and TNFi cohorts was done on last observation carried forward up to 12 (±3) mo, with non-response imputation for pts who had stopped/switched initial treatment. Logistic regression analysis was used, including propensity score (PS) analysis to adjust for imbalanced prognostic baseline (BL) covariates: country, age, sex, BMI, smoking (yes/no), comorbidities (cardiovascular/metabolic syndrome), PsA type (axial, polyarticular, oligoarticular), psoriasis body surface area (BSA), disease duration, cDAPSA, 12-item PsA Impact of Disease (PsAID-12), dactylitis, enthesitis, Fibromyalgia Rapid Screening Tool (FiRST) score, line of biologic (b)DMARD, synthetic DMARD use, and steroid or NSAID use.Results:Of 929 eligible pts, 893 had evaluable data at BL and at follow-up; 438 (95.6%) were treated with UST and 455 (96.6%) with TNFi (including stoppers/switchers). UST and TNFi groups had BL differences in mean age (51.0 vs 48.5 years, respectively), concurrent comorbidities (68.7% vs 60.9%), time since diagnosis (7.5 vs 6.2 years), line of treatment (1st-line 45.0% vs 55.2%; 3rd-line 20.5% vs 12.1%), NSAID use (54.8% vs 68.8%), concomitant MTX use (29.9% vs 42.0%) and psoriasis skin involvement (BSA >10% in 26.6% vs 14.8%).In 714 pts with available data, mean (standard deviation) BL cDAPSA was 30.6 (20.2; n=358) for UST and 29.3 (18.6; n=356) for TNFi. Observed data showed differences in proportion of pts achieving MDA/VLDA and cDAPSA LDA/remission in favour of TNFi, but after PS adjustment for BL differences (such as line of therapy, skin psoriasis, concomitant conventional DMARD, etc.), odds ratios for reaching targets at 12 mo did not significantly differ between UST and TNFi groups (Fig. 1).Comparison of 6- and 12-mo unadjusted data showed sustained MDA/VLDA responses with both UST (21.8%) and TNFi (29.5%), with comparable proportions of additional pts achieving these targets between 6 and 12 mo (17.0% and 20.3%, respectively). Sustained efficacy became lower with successive lines of treatment (data not shown).Conclusion:Various factors, including patient characteristics such as comorbidities, influence the physician’s selection of treatment modality for patients needing a bDMARD. Our real-world results demonstrate differences in observed clinical effectiveness between UST and TNFi. However, after PS adjustment for a number of BL differences, clinical results at 12 mo were comparable between UST and TNFi groups. Data at 12 mo also show sustained response with both UST and TNFi treatment, as well as a similar rate of pts achieving targets after 6 to 12 mo of treatment.Acknowledgments:This study was funded by Janssen.Disclosure of Interests:Josef S. Smolen Grant/research support from: AbbVie, AstraZeneca, Celgene, Celltrion, Chugai, Eli Lilly, Gilead, ILTOO, Janssen, Novartis-Sandoz, Pfizer Inc, Samsung, Sanofi, Consultant of: AbbVie, AstraZeneca, Celgene, Celltrion, Chugai, Eli Lilly, Gilead, ILTOO, Janssen, Novartis-Sandoz, Pfizer Inc, Samsung, Sanofi, Stefan Siebert Grant/research support from: BMS, Boehringer Ingelheim, Celgene, GlaxoSmithKline, Janssen, Novartis, Pfizer, UCB, Consultant of: AbbVie, Boehringer Ingelheim, Janssen, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, Celgene, Janssen, Novartis, Tatiana Korotaeva Grant/research support from: Pfizer, Consultant of: Abbvie, BIOCAD, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Novartis-Sandoz, Pfizer, UCB, Speakers bureau: Abbvie, BIOCAD, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Novartis-Sandoz, Pfizer, UCB, Paul Bergmans Shareholder of: Johnson & Johnson, Employee of: Janssen, Kurt de Vlam Consultant of: Celgene Corporation, Eli Lilly, Novartis, Pfizer, UCB – consultant, Speakers bureau: Celgene Corporation, Eli Lilly, Novartis, Pfizer, UCB – speakers bureau and honoraria, Elisa Gremese Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Sanofi, UCB, Roche, Pfizer, Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Sanofi, UCB, Roche, Pfizer, Beatriz Joven-Ibáñez Speakers bureau: Abbvie, Celgene, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Wim Noel Employee of: Janssen Pharmaceuticals NV, Michael T Nurmohamed Grant/research support from: Abbvie, Bristol-Myers Squibb, Celltrion, GlaxoSmithKline, Jansen, Eli Lilly, Menarini, Merck Sharp & Dohme, Mundipharma, Pfizer, Roche, Sanofi, USB, Consultant of: Abbvie, Bristol-Myers Squibb, Celltrion, GlaxoSmithKline, Jansen, Eli Lilly, Menarini, Merck Sharp & Dohme, Mundipharma, Pfizer, Roche, Sanofi, USB, Speakers bureau: Abbvie, Bristol-Myers Squibb, Celltrion, GlaxoSmithKline, Jansen, Eli Lilly, Menarini, Merck Sharp & Dohme, Mundipharma, Pfizer, Roche, Sanofi, USB, Petros Sfikakis Grant/research support from: Grant/research support from Abvie, Novartis, MSD, Actelion, Amgen, Pfizer, Janssen Pharmaceutical, UCB, Elke Theander Employee of: Janssen-Cilag Sweden AB, Laure Gossec Grant/research support from: Lilly, Mylan, Pfizer, Sandoz, Consultant of: AbbVie, Amgen, Biogen, Celgene, Janssen, Lilly, Novartis, Pfizer, Sandoz, Sanofi-Aventis, UCB

Oral apremilast in the treatment of active psoriatic arthritis: Results of a multicenter, randomized, double-blind, placebo-controlled study

2012 ◽  
pp. n/a-n/a ◽  
Author(s):  
Georg Schett ◽  
Jurgen Wollenhaupt ◽  
Kim Papp ◽  
Rik Joos ◽  
Jude F. Rodrigues ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Controlled Study ◽  
Double Blind ◽  
Double Blind Placebo

scholarly journals Effectiveness ofLactobacillus helveticusandLactobacillus rhamnosusfor the management of antibiotic-associated diarrhoea in healthy adults: a randomised, double-blind, placebo-controlled trial

2016 ◽  
Vol 116 (1) ◽  
pp. 94-103 ◽  
Author(s):  
Malkanthi Evans ◽  
Ryan P. Salewski ◽  
Mary C. Christman ◽  
Stephanie-Anne Girard ◽  
Thomas A. Tompkins
Keyword(s):  
Rating Scale ◽  
Gastrointestinal Symptoms ◽  
Healthy Adults ◽  
Lactobacillus Helveticus ◽  
Primary Study ◽  
Gastrointestinal Microbiota ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Probiotic Intervention ◽  
Antibiotic Associated Diarrhoea

AbstractBroad-spectrum antibiotic use can disrupt the gastrointestinal microbiota resulting in diarrhoea. Probiotics may be beneficial in managing this type of diarrhoea. The aim of this 10-week randomised, double-blind, placebo-controlled, parallel study was to investigate the effect ofLactobacillus helveticusR0052 andLactobacillus rhamnosusR0011 supplementation on antibiotic-associated diarrhoea in healthy adults. Subjects were randomised to receive 1 week of amoxicillin–clavulanic acid (875 mg/125 mg) once per day, plus a daily dose of 8×109colony-forming units of a multi-strain probiotic (n80) or placebo (n80). The probiotic or placebo intervention was maintained for 1 week after completion of the antibiotic. Primary study outcomes of consistency and frequency of bowel movements were not significantly different between the probiotic and placebo groups. The secondary outcomes of diarrhoea-like defecations, Gastrointestinal Symptoms Rating Scale scores, safety parameters and adverse events were not significantly different between the probiotic intervention and the placebo. Apost hocanalysis on the duration of diarrhoea-like defecations showed that probiotic intervention reduced the length of these events by 1 full day (probiotic, 2·70(sem0·36) d; placebo, 3·71 (sem0·36) d;P=0·037; effect size=0·52). In conclusion, this study provides novel evidence thatL. helveticusR0052 andL. rhamnosusR0011 supplementation significantly reduced the duration of diarrhoea-like defecations in healthy adults receiving antibiotics.

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