scholarly journals Responses to Adalimumab in Patients with Active Psoriatic Arthritis Who Have Not Adequately Responded to Prior Therapy: Effectiveness and Safety Results From an Open-label Study

2010 ◽  
Vol 37 (9) ◽  
pp. 1898-1906 ◽  
Author(s):  
DAFNA D. GLADMAN ◽  
JOHN S. SAMPALIS ◽  
OLIVIER ILLOUZ ◽  
BENOÎT GUÉRETTE
Keyword(s):  
Psoriatic Arthritis ◽  
Physical Function ◽  
Response Rates ◽  
Target Lesion ◽  
Inadequate Response ◽  
Open Label ◽  
Open Label Study ◽  
Label Study ◽  
Prior Therapy ◽  
Link Type

Objective.To evaluate the effectiveness and safety of adalimumab in patients with active psoriatic arthritis (PsA) and an inadequate response to prior therapy.Methods.Patients were treated with subcutaneous injections of adalimumab 40 mg every other week in addition to their standard antirheumatic therapies in a 12-week, open-label study. Effectiveness evaluations at Week 12 included American College of Rheumatology (ACR) and Psoriasis Area and Severity Index (PASI) response rates, Psoriatic Arthritis Response Criteria (PsARC), active dactylitis, enthesitis, and target lesion assessment. Physical function was evaluated using the Health Assessment Questionnaire Disability Index (HAQ-DI).Results.A total of 127 patients were enrolled. At Week 12, patients achieved ACR20, ACR50, and ACR70 response rates of 78.0%, 55.9%, and 21.3%, respectively. PASI50 and PASI75 response rates were 64.7% and 47.1%. A PsARC response was experienced by 70.1% of patients. Between baseline and Week 12, clinically and statistically significant reductions occurred in the mean total plaque score of the target lesion as well as in the percentages of patients with active dactylitis and enthesitis. A mean improvement in HAQ-DI was also observed (−0.44; p < 0.001). Three serious adverse events were reported, but none was considered related to adalimumab therapy.Conclusion.Adalimumab-treated patients achieved significant improvements in both skin and joint manifestations of PsA, as well as in physical function. Adalimumab was well tolerated and had a safety profile similar to that observed in other clinical trials of adalimumab for the treatment of PsA. ClinicalTrials.gov identifier: NCT00427362.

scholarly journals Safety of Rituximab in Combination with Other Biologic Disease-modifying Antirheumatic Drugs in Rheumatoid Arthritis: An Open-label Study

2013 ◽  
Vol 40 (5) ◽  
pp. 599-604 ◽  
Author(s):  
William F.C. Rigby ◽  
Philip J. Mease ◽  
Ewa Olech ◽  
Mark Ashby ◽  
Swati Tole
Keyword(s):  
Rheumatoid Arthritis ◽  
Joint Disease ◽  
Inadequate Response ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
Open Label ◽  
Open Label Study ◽  
Label Study ◽  
Link Type ◽  
Disease Modifying

Objective.To characterize the safety of rituximab (RTX) in combination with biologic disease-modifying antirheumatic drugs (DMARD) in patients with rheumatoid arthritis (RA).Methods.We did an open-label study of the safety and efficacy of RTX in adult patients with active RA and an inadequate response to ≥ 1 biologic for ≥ 12 weeks (stable dose ≥ 4 weeks). RTX (2 × 500 mg) was added to patients’ current biologic and nonbiologic DMARD treatment. After 24 weeks, patients with 28-joint Disease Activity Score ≥ 2.6 were eligible for RTX retreatment. The primary endpoint was the proportion of patients developing a serious adverse event (SAE) within 24 weeks of initiating RTX.Results.Patients (n = 176) received RTX with 18 different biologic/DMARD combinations. Adalimumab alone (n = 46; 26.1%) or etanercept alone (n = 37; 21.0%) plus RTX were the most common combinations. Overall, 90.9% and 76.1% of patients completed 24 and 48 weeks, respectively; 147 patients (83.5%) received a second course of RTX. Over 24 weeks, 9.1% of patients reported SAE (24.3 events/100 patient-yrs, 95% CI 15.5–38.1). The SAE rate was similar over 48 weeks (22.4 events/100 patient-yrs, 95% CI 15.9–31.5). Four serious infections were reported over 48 weeks (2.7 events/100 patient-yrs, 95% CI 1.0–7.2). No SAE occurred within 24 h of any RTX infusion. Efficacy responses improved numerically at Week 48 compared with Week 24.Conclusion.The overall safety profile of RTX in combination with 1 other biologic was consistent with that previously reported for RTX plus methotrexate or other nonbiologic DMARD. (Clinicaltrials.govNCT00443651)

scholarly journals Effects of Probiotic Strains on Disease Activity and Enteric Permeability in Psoriatic Arthritis–A Pilot Open-Label Study

Nutrients ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2337
Author(s):  
Andreas Haidmayer ◽  
Philipp Bosch ◽  
Angelika Lackner ◽  
Monica D’Orazio ◽  
Johannes Fessler ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Disease Activity ◽  
Th17 Cells ◽  
Intestinal Inflammation ◽  
Gut Permeability ◽  
Open Label ◽  
Open Label Study ◽  
Label Study ◽  
Immune Phenotyping ◽  
Probiotic Strains

(1) Background: Psoriatic Arthritis (PsA) is a painful disease of the joints and spine. Recent reports observed distinct enteric dysbiosis in PsA; intake of probiotic strains is considered to ameliorate enteric dysbiosis. If probiotics are effective in PsA is elusive. (2) Methods: In this pilot open-label study we enrolled 10 PsA patients with low to medium disease activity who received probiotics for 12 weeks. Analysis of faecal zonulin, α1-antitrypsin and calprotectin, as well as peripheral immune phenotyping was performed at baseline, after 12 weeks and 12 weeks after termination of probiotic intake. (3) Results: All patients showed increased levels of the enteric permeability marker zonulin which correlated with the frequency of peripheral Th17 cells. Calprotectin, a marker for intestinal inflammation was elevated in 6 out of 10 patients. Probiotic intake resulted in a reduction of disease activity and gut permeability. These effects, however, were not sustained beyond termination of probiotic intake. (4) Conclusions: PsA patients suffer from enhanced enteric permeability and inflammation. Probiotics may ameliorate disease activity in PsA by targeting these alterations.

scholarly journals Post-intervention status in patients with refractory myasthenia gravis treated with eculizumab during REGAIN and its open-label extension

Neurology ◽  
2020 ◽  
pp. 10.1212/WNL.0000000000011207
Author(s):  
Renato Mantegazza ◽  
Gil I. Wolfe ◽  
Srikanth Muppidi ◽  
Heinz Wiendl ◽  
Kenji P. Fujita ◽  
...  
Keyword(s):  
Myasthenia Gravis ◽  
Controlled Trial ◽  
Open Label ◽  
Post Intervention ◽  
Open Label Study ◽  
Label Study ◽  
Link Type ◽  
Open Label Extension ◽  
Anti Acetylcholine

ObjectiveTo evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) to achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN and its open-label extension.MethodsPatients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study.ResultsA total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1–4.5). After 130 weeks of eculizumab treatment, 87.1% of patients achieved improved status and 57.1% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected.ConclusionsEculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population.Classification of evidenceThis study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo.Trial registrationREGAIN, NCT01997229; REGAIN open-label extension, NCT02301624 (ClinicalTrials.gov).

scholarly journals Prospective, Randomized, Parallel-Group, Open-Label Study to Evaluate the Efficacy and Safety of IMU-838, in Combination with Oseltamivir, in Adults with Coronavirus Disease 19 The IONIC Trial

2021 ◽  
Author(s):  
Kavi Sharma ◽  
Dr Lisa Berry ◽  
Dr Evangelos Vryonis ◽  
Dr Asad Ali ◽  
Dr Beatriz Lara ◽  
...  
Keyword(s):  
Clinical Improvement ◽  
Trial Design ◽  
Standard Of Care ◽  
Ordinal Scale ◽  
Therapeutic Effects ◽  
Open Label ◽  
Open Label Study ◽  
Label Study ◽  
Link Type ◽  
Discharge From Hospital

Background: Globally there is a scarcity of effective treatments for SARS-CoV-2 infections (causing COVID 19). Repurposing existing medications may offer the best hope for treating COVID 19 patients to curb the pandemic. IMU-838 is a dihydroorotate dehydrogenase (DHODH) inhibitor, which is an effective mechanism for antiviral effects against respiratory viruses. When used synergistically with Oseltamivir, therapeutic effects have been observed against influenza and SARS-CoV-2 in rodents.(13) The IONIC trial is a randomized control trial that will investigate whether time to clinical improvement in COVID 19 patients is improved following a 14 day course of IMU-838 + Oseltamivir versus Oseltamivir alone. Methods: IONIC trial is an open label study in which participants will be randomised 1:1 in two parallel arms; the intervention arm (IMU-838 + Oseltamivir) and control arm (Oseltamivir only). The primary outcome is time-to-clinical improvement; defined as the time from randomisation to: a 2-point improvement on WHO ordinal scale; discharge from hospital, or death (whichever occurs first). The study is sponsored by UHCW NHS Trust and funded by LifeArc. Discussion: The IONIC Protocol describes an overarching trial design to provide reliable evidence on the efficacy of IMU-838 (vidofludimus calcium) when delivered in combination with an antiviral therapy (Oseltamivir) [IONIC Intervention] for confirmed or suspected COVID-19 infection in adult patients receiving usual standard of care. Trial Registration: The trial was registered with EudraCT (2020-001805-21) on 09.04.2020 and ISRCTN on 23.09.2020 (ISRCTN53038326) and Clinicaltrials.gov on 17.08.2020 (NCT04516915) Strengths and Limitations: This study is the first to recruit participants in the trial exploring the effectiveness of IMU-838 in COVID-19. In addition, we believe it is the only trial exploring the effectiveness of IMU-838 in combination with Oseltamivir (Tamiflu) in patients with moderate to severe COVID-19. However, to make the trial design flexible due to the on-going pandemic the trial is un-blinded.

scholarly journals Long-term safety and efficacy of sarilumab plus methotrexate on disease activity, physical function and radiographic progression: 5 years of sarilumab plus methotrexate treatment

RMD Open ◽  
2019 ◽  
Vol 5 (2) ◽  
pp. e000887 ◽  
Author(s):  
Mark C Genovese ◽  
Désirée van der Heijde ◽  
Yong Lin ◽  
Gregory St John ◽  
Sheldon Wang ◽  
...  
Keyword(s):  
Disease Activity ◽  
Physical Function ◽  
Clinical Efficacy ◽  
Radiographic Progression ◽  
Activity Index ◽  
Inadequate Response ◽  
Open Label ◽  
Link Type ◽  
Number Of Patients ◽  
Open Label Extension

ObjectiveIn MOBILITY (NCT01061736), sarilumab significantly reduced disease activity, improved physical function and inhibited radiographic progression at week 52 versus placebo in patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate. We report 5-year safety, efficacy and radiographic outcomes of sarilumab from NCT01061736 and the open-label extension (EXTEND; NCT01146652), in which patients received sarilumab 200 mg every 2 weeks (q2w) + methotrexate.MethodsPatients (n=1197) with moderately to severely active RA were initially randomised to placebo, sarilumab 150 mg or sarilumab 200 mg subcutaneously q2w plus weekly methotrexate for 52 weeks. Completers were eligible to enrol in the open-label extension and receive sarilumab 200 mg q2w + methotrexate.ResultsOverall, 901 patients entered the open-label extension. The safety profile remained stable over 5-year follow-up and consistent with interleukin-6 receptor blockade. Absolute neutrophil count <1000 cells/mm3 was observed but not associated with increased infection rate. Initial treatment with sarilumab 200 mg + methotrexate was associated with reduced radiographic progression over 5 years versus sarilumab 150 mg + methotrexate or placebo + methotrexate (mean±SE change from baseline in van der Heijde-modified Total Sharp Score: 1.46±0.27, 2.35±0.28 and 3.68±0.27, respectively (p<0.001 for each sarilumab dose versus placebo)). Clinical efficacy was sustained through 5 years according to Disease Activity Score (28-joint count) using C reactive protein, Clinical Disease Activity Index (CDAI) and Health Assessment Questionnaire-Disability Index. The number of patients achieving CDAI ≤2.8 at 5 years was similar among initial randomisation groups (placebo, 76/398 (19%); sarilumab 150 mg, 68/400 (17%); sarilumab 200 mg, 84/399 (21%)).ConclusionClinical efficacy, including inhibition of radiographic progression, reduction in disease activity and improvement in physical function, was sustained with sarilumab + methotrexate over 5 years. Safety appeared stable over the 5-year period.

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