scholarly journals AB0630 PEGLOTICASE/METHOTREXATE CO-THERAPY IMPROVED JOINT AND PATIENT-REPORTED HEALTH ASSESSMENTS IN PATIENTS WITH UNCONTROLLED GOUT: 12-MONTH EXPLORATORY OUTCOMES OF THE MIRROR OPEN-LABEL TRIAL

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1348.2-1349
Author(s):  
J. Botson ◽  
P. M. Peloso ◽  
K. Obermeyer ◽  
B. Lamoreaux ◽  
L. Zhao ◽  
...  
Keyword(s):  
Bone Erosion ◽  
Responder Rate ◽  
Health Improvement ◽  
Research Support ◽  
Open Label ◽  
Clinical Patient ◽  
Mitt Population ◽  
Patient Reported ◽  
Reported Health ◽  
Open Label Trial

Background:Gout development follows persistent serum uric acid (sUA) elevation. Patients who are refractory to or cannot tolerate oral urate lowering therapies (ULTs) have limited treatment options. Pegloticase is effective in treating refractory gout, but many patients develop anti-drug antibodies (ADAs), which are associated with loss of urate-lowering efficacy1-3 and infusion reactions (IRs).1,2 In phase 3 trials, the pooled pegloticase responder rate during Months 3 and 6 combined was 42% (8 mg infusion every 2 weeks), with high-titer ADA positive patients losing efficacy prior to 6 months.1 The 6-month results from the MIRROR open-label trial (79% response rate [11/14], 95%CI 49-95%)4 suggest that methotrexate (MTX) administered in conjunction with pegloticase increases treatment responder rate.Objectives:To examine longer-term (12-month) exploratory endpoints from the MIRROR open-label trial, including joint, overall health, and gout global assessments. Serial dual-energy computed tomography (DECT) images were also examined when available.Methods:Adult patients with uncontrolled gout (sUA ≥6 mg/dL with ≥1 of the following: sUA ≥6 mg/dL despite ULT use, intolerance to ULT, or functionally limiting tophaceous deposits) were included. Patients with immunocompromised status, G6PD deficiency, severe renal impairment, or MTX contraindication were excluded. Patients were administered oral MTX (15 mg/week) and folic acid (1 mg/day) 4 weeks prior to and throughout pegloticase therapy (8 mg biweekly infusion for up to 52 weeks). Exploratory outcomes included mean change from baseline (CFB) in number of affected joints (tophi, swollen, tender), Health Assessment Questionnaire (HAQ) scores (Disability Index [DI; score 0−3], Pain [score 0−100], Health [score 0−100]), and Gout Global Assessments (Patient, Physician; score 0−10). A decrease in these measures reflects clinical/patient-reported health improvement. Change in urate deposition volume, as measured on DECT imaging, was also examined as available. Analyses were performed on the modified intent-to-treat (mITT) population (≥1 pegloticase infusion received).Results:14 patients (all male, mean±SD age: 49.3±8.7 years) made up the mITT population. Mean±SD sUA prior to pegloticase treatment was 9.2±2.5 mg/dL and 13 patients had visible tophi. 3 patients discontinued due to 2 consecutive sUA levels >6 mg/dL and 1 patient completed the study at week 24 (pre-protocol amendment extending treatment from 24 to 52 weeks). 10 patients completed the 52-week study. Of these, 8 patients received 26 infusions and 2 patients received 12 infusions, discontinued pegloticase after meeting their treatment goal at 24 weeks, and started allopurinol while remaining in study under observation. At week 52 (n=10, sUA=1.1±2.5 mg/dL), the number of affected joints improved, along with HAQ measures (Figure 1). Global Assessments of Gout also improved (Physician: CFB=-5.7±2.6, Patient CFB=-4.6±2.1) and majority of subjects had a score of 0 or 1 (0=“excellent health”) at week 52 (Physician: 0.3±0.5, Patient: 1.1±1.3). Two patients had available DECT imaging. One received pegloticase/methotrexate co-therapy thru week 52 and had a marked reduction in total urate volume (baseline: 128.76 cm3, week 52: 1.33 cm3). The other received only 5 pegloticase infusions, but also showed total urate volume reduction (baseline: 59.20 cm3, week 10: 25.07 cm3). Both patients displayed improvement in bone erosion healing.Conclusion:These 12-month exploratory endpoints of the MIRROR open-label trial suggest that MTX/pegloticase co-therapy results in meaningful changes in clinical evaluations (tophaceous, tender, and swollen joint counts), and patient-reported outcomes (pain, disability) in patients with uncontrolled gout.References:[1]Sundy JS et al. JAMA 2011;306:711-20[2]Baraf HS et al. J Clin Rheumatol 2014;20:427-32[3]Lipsky PE et al. Arthritis Res Ther 2014, 16:R60[4]Botson JK et al. J Rheum 2020 [Epub ahead of print]Disclosure of Interests:John Botson Speakers bureau: Horizon Therapeutics, Celgene, Novartis, and AbbVie, Consultant of: Horizon Therapeutics, Celgene, Novartis, and AbbVie, Grant/research support from: Horizon Therapeutics and Radius Health, Paul M. Peloso Shareholder of: Horizon Therapeutics plc, Employee of: Horizon Therapeutics plc, Katie Obermeyer Shareholder of: Horizon Therapeutics plc, Employee of: Horizon Therapeutics plc, Brian LaMoreaux Shareholder of: Horizon Therapeutics plc, Employee of: Horizon Therapeutics plc, Lin Zhao Shareholder of: Horizon Therapeutics plc, Employee of: Horizon Therapeutics plc, Michael E. Weinblatt Shareholder of: Lycera, Can-Fite BioPharma, Scipher Medicine, Inmedix, and Vorso, Consultant of: Bristol Myers Squibb, Corona, Lilly, AbbVie, Amgen, Arena, GlaxoSmithKline, Gilead Sciences, Horizon Therapeutics, Lycera, Novartis, Pfizer, Roche, Samsung, Scipher Medicine, and Set Point, Grant/research support from: Amgen, Bristol-Myers Squibb, Crescendo Bioscience, Lilly and Sanofi, Jeff Peterson Speakers bureau: Horizon Therapeutics plc, Grant/research support from: Horizon Therapeutics plc.

scholarly journals The efficacy of corticosteroids therapy in patients with moderate to severe SARS-CoV-2 infection: a multicenter, randomized, open-label trial

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Mostafa Ghanei ◽  
Masoud Solaymani-Dodaran ◽  
Ali Qazvini ◽  
Amir Hosein Ghazale ◽  
Seyed Amin Setarehdan ◽  
...  
Keyword(s):  
Hospital Stay ◽  
Length Of Hospital Stay ◽  
Diabetic Patients ◽  
Open Label ◽  
Mitt Population ◽  
Treatment Regimens ◽  
Clinical Recovery ◽  
Group I ◽  
The Mean ◽  
Open Label Trial

Abstract Background We performed a multicenter, randomized open-label trial in patients with moderate to severe Covid-19 treated with a range of possible treatment regimens. Methods: Patients were randomly assigned to one of three regimen groups at a ratio of 1:1:1. The primary outcome of this study was admission to the intensive care unit. Secondary outcomes were intubation, in-hospital mortality, time to clinical recovery, and length of hospital stay (LOS). Between April 13 and August 9, 2020, a total of 336 patients were randomly assigned to receive one of the 3 treatment regimens including group I (hydroxychloroquine stat, prednisolone, azithromycin and naproxen; 120 patients), group II (hydroxychloroquine stat, azithromycin and naproxen; 116 patients), and group III (hydroxychloroquine and lopinavir/ritonavir (116 patients). The mean LOS in patients receiving prednisolone was 5.5 in the modified intention-to-treat (mITT) population and 4.4 days in the per-protocol (PP) population compared with 6.4 days (mITT population) and 5.8 days (PP population) in patients treated with Lopinavir/Ritonavir. Results The mean LOS was significantly lower in the mITT and PP populations who received prednisolone compared with populations treated with Lopinavir/Ritonavir (p = 0.028; p = 0.0007). We observed no significant differences in the number of deaths, ICU admission, and need for mechanical ventilation between the Modified ITT and per-protocol populations treated with prednisolone and Lopinavir/Ritonavir, although these outcomes were better in the arm treated with prednisolone. The time to clinical recovery was similar in the modified ITT and per-protocol populations treated with prednisolone, lopinavir/ritonavir, and azithromycin (P = 0.335; P = 0.055; p = 0.291; p = 0.098). Conclusion The results of the present study show that therapeutic regimen (regimen I) with low dose prednisolone was superior to other regimens in shortening the length of hospital stay in patients with moderate to severe COVID-19. The steroid sparing effect may be utilized to increase the effectiveness of corticosteroids in the management of diabetic patients by decreasing the dosage.

Patient-reported most bothersome symptoms in OAB: post hoc analysis of data from a large, open-label trial of solifenacin

2009 ◽  
Vol 20 (6) ◽  
pp. 667-675 ◽  
Author(s):  
Peter K. Sand ◽  
William D. Steers ◽  
Roger Dmochowski ◽  
Masakazu Andoh ◽  
Sergio Forero-Schwanhaeuser
Keyword(s):  
Open Label ◽  
Post Hoc Analysis ◽  
Patient Reported ◽  
Open Label Trial ◽  
Post Hoc

scholarly journals A Multicentre, Efficacy and Safety Study of Methotrexate to Increase Response Rates in Patients With Uncontrolled Gout Receiving Pegloticase (MIRROR): 12-Month Efficacy, Safety, Immunogenicity, and Pharmacokinetic Findings of an Open-label Study

2021 ◽  
Author(s):  
John Botson ◽  
John RP Tesser ◽  
Ralph Bennett ◽  
Howard M Kenney ◽  
Paul M Peloso ◽  
...  
Keyword(s):  
Safety Data ◽  
Response Rates ◽  
Serum Urate ◽  
Responder Rate ◽  
Open Label ◽  
Open Label Study ◽  
Quantitation Limit ◽  
Immunocompromised Status ◽  
Trough Concentrations ◽  
Open Label Trial

Abstract Background: Publications suggest immunomodulation co-therapy improves responder rates in uncontrolled/refractory gout patients undergoing pegloticase treatment. The MIRROR open-label trial showed a 6-month pegloticase+methotrexate co-therapy responder rate of 79%, compared to an established 42% pegloticase monotherapy responder rate. Longer-term efficacy/safety data are presented here.Methods: Uncontrolled gout patients (serum urate [SU]≥6 mg/dL and SU≥6 mg/dL despite urate-lowering therapy [ULT], ULT intolerance, or functionally-limiting tophi) were included. Patients with immunocompromised status, G6PD deficiency, severe kidney disease, or methotrexate contraindication were excluded. Oral methotrexate (15 mg/week) and folic acid (1 mg/day) were administered 4-weeks before and during pegloticase therapy. Twelve-month responder rate (SU<6 mg/dL for ≥80% during Month 12), 52-week change from baseline in SU, and extended safety were examined. Efficacy analyses were performed for patients receiving ≥1 pegloticase infusion. PK/anti-drug antibodies (ADAs) were examined and related to efficacy/safety findings. Results: Fourteen patients were included (all male, 49.3 ± 8.7 years, 13.8 ± 7.4 year gout history, pre-therapy SU: 9.2 ± 2.5 mg/dL). Three patients were non-responders and discontinued study treatment before 24-weeks, one patient exited the study per-protocol at 24-weeks (enrolled prior to treatment extension amendment), and 10 remained in study through Week 52. Of the 10, 8 completed 52-weeks of pegloticase+methotrexate and were 12-month responders. The remaining two discontinued pegloticase+methotrexate at Week 24 (met treatment goals) and stayed in study under observation (allopurinol prescribed at physicians’ discretion); one remained a responder at 12-months. At 52-weeks, change from baseline in SU was -8.2 ± 4.1 mg/dL (SU: 1.1 ± 2.4 mg/dL, n=10). Gout flares were common early in treatment but progressively decreased while on therapy (Weeks 1-12: 13/14 [92.9%], Weeks 36-52: 2/8 [25.0%]). One patient recovered from sepsis (serious AE). Two non-responders developed high ADA titres; fewer patients had trough concentrations (Cmin) below quantitation limit (BQL) and median Cmin was higher (1.03 mg/mL vs. BQL) than in pegloticase monotherapy trials.Conclusions: Methotrexate+pegloticase co-therapy was well-tolerated over 12-months, with sustained SU lowering, progressive gout flare reduction, and no new safety concerns. Antibody/PK findings suggest methotrexate attenuates ADA formation, coincident with higher treatment response rates.Trial registration: ClinicalTrials.gov: NCT03635957, registered 17 August 2018, https://clinicaltrials.gov/ct2/show/NCT03635957

scholarly journals A novel cell-free formulation for the treatment of knee osteoarthritis generates better patient-reported health outcomes in more severe cases

2020 ◽  
Vol 28 (2) ◽  
pp. 230949902093812
Author(s):  
Ivan Delgado-Enciso ◽  
Juan Paz-Garcia ◽  
Jose Valtierra-Alvarez ◽  
Jorge Preciado-Ramirez ◽  
Bertha A Olmedo-Buenrostro ◽  
...  
Keyword(s):  
Knee Osteoarthritis ◽  
Health Outcomes ◽  
Sleep Disturbances ◽  
Sleep Problems ◽  
Severe Disease ◽  
Womac Score ◽  
Open Label ◽  
Knee Oa ◽  
Patient Reported ◽  
Reported Health

Background: The bioactive cell-free formulation (BIOF2) for cartilage regeneration has shown a major therapeutic response in severe knee osteoarthritis. However, its effect on patients with mild or moderate stages of the disease has not been studied. Objective: To evaluate the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, minimal clinically important improvement (MCII) and sleep disturbances in mild, moderate, and severe stages of knee osteoarthritis (OA) with the novel cell-free formulation treatment (BIOF2). Methods: An open-label, nonrandomized, baseline-controlled, parallel group study on patients with mild, moderate, and severe knee OA was conducted to evaluate the effect of intra-articular administration of BIOF2. Clinical improvement was determined through the WOMAC score and MCII, whereas sleep disturbances were measured through a Likert scale questionnaire. Results: At 6 months post-treatment, the mean decrease in the total WOMAC score was 16.4 +/- 4.7%, 49.9 +/- 6.4%, and 62.7 +/- 4.5% in the patients with mild, moderate, and severe disease, respectively ( p < 0.001, analysis of variance test). MCII at 6 months was 18%, 78%, and 100% for mild, moderate, and severe disease, respectively ( p < 0.001, likelihood-ratio χ 2 test). Concerning sleep disturbances, 60% of the patients with severe OA had important sleep problems before beginning treatment, and those difficulties were overcome 6 months after treatment. Only 18% of the patients with mild disease and 16% with moderate disease had serious sleep disturbances at the beginning of the study, and there was slight improvement after treatment. No adverse events were recorded during follow-up. Conclusion: BIOF2 generates better patient-reported health outcomes (on pain, stiffness, function, and sleep) in the more severe cases of knee OA.

Sign in / Sign up

Export Citation Format

Share Document