ABSTRACT
Chemotherapy-induced thrombocytopenia (CIT) is a common challenge of cancer therapy and can lead to chemotherapy dose reduction, delay, and/or discontinuation, affecting relative dose intensity, and possibly adversely impacting cancer care. Besides changing anticancer regimens, standard management of CIT has been limited to platelet transfusions and supportive care. Use of the thrombopoietin receptor agonist romiplostim, already approved for use in immune thrombocytopenia, has shown promising signs of efficacy in CIT. In a phase 2 prospective randomized study of solid tumor patients with platelet counts <100 × 109/L for ≥4 weeks due to CIT, weekly romiplostim corrected the platelet count to >100 × 109/L in 93% (14/15) of patients within 3 weeks versus 12.5% (1/8) of untreated patients (p < 0.001). Including patients treated with romiplostim in an additional single-arm cohort, 85% (44/52) of all romiplostim-treated patients responded with platelet count correction within 3 weeks. Several retrospective studies of CIT have also shown responses to weekly romiplostim, with the largest study finding that poor response to romiplostim was predicted by tumor invasion of the bone marrow (odds ratio, 0.029; 95% CI: 0.0046-0.18; p < 0.001), prior pelvic irradiation (odds ratio, 0.078; 95% CI: 0.0062-0.98; p = 0.048), and prior temozolomide treatment (odds ratio 0.24; 95% CI: 0.061-0.96; p = 0.043). Elsewhere, lower baseline TPO levels were predictive of romiplostim response (p = 0.036). No new safety signals have emerged from romiplostim CIT studies. Recent treatment guidelines, including those from the National Comprehensive Cancer Network, now support consideration of romiplostim use in CIT. Data are expected from two ongoing phase 3 romiplostim CIT trials.
Subject(s)
Antineoplastic Agents , Receptors, Fc , Recombinant Fusion Proteins , Thrombocytopenia , Thrombopoietin , Humans , Receptors, Fc/therapeutic use , Thrombopoietin/therapeutic use , Thrombopoietin/adverse effects , Recombinant Fusion Proteins/therapeutic use , Recombinant Fusion Proteins/adverse effects , Recombinant Fusion Proteins/administration & dosage , Thrombocytopenia/drug therapy , Thrombocytopenia/chemically induced , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Neoplasms/drug therapy , Platelet Count , Receptors, Thrombopoietin/agonists , Treatment OutcomeABSTRACT
BACKGROUND: Romiplostim, a thrombopoietin analog, is commonly used to treat immune-mediated thrombocytopenia (ITP) in humans, but its use in dogs remains limited. OBJECTIVES: Evaluate the effects and adverse events of romiplostim administration in dogs with thrombocytopenia caused by various underlying diseases. ANIMALS: Forty-two client-owned dogs with naturally occurring thrombocytopenia at 2 referral animal hospitals. METHODS: Retrospective, multi-institutional analysis to evaluate the outcomes of romiplostim treatment in dogs. RESULTS: Among the dogs treated with romiplostim, 27 experienced an increase in platelet count and 26 maintained a platelet count within the reference range. Platelet count improvement was observed in various conditions: primary ITP (90%, n = 18/20), pancytopenia of unknown etiology (42.9%, n = 3/7), chemotherapy-induced thrombocytopenia (50%, n = 3/6), babesiosis (100%, n = 1/1), radiotherapy-induced thrombocytopenia (0%, n = 0/1), and disseminated intravascular coagulopathy (33.3%, n = 2/6). The median time for platelet recovery (>50 000/µL) after romiplostim administration was 4 days, and the median time for platelet count normalization was 7 days. Median hospitalization time for the improvement group (I) was 5 days. The survival-to-discharge rates were 85%, 40%, and 28.6% for dogs with primary ITP, secondary thrombocytopenia, and thrombocytopenia of unknown etiology, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: Romiplostim is a well-tolerated and promising treatment for primary ITP in dogs, suggesting its potential as a valuable therapeutic option for dogs with thrombocytopenia caused by various underlying conditions. These findings emphasize the need for further research to optimize romiplostim dosing and understand its role in treating secondary thrombocytopenia and pancytopenia of unknown etiology.
Subject(s)
Dog Diseases , Receptors, Fc , Recombinant Fusion Proteins , Thrombocytopenia , Thrombopoietin , Dogs , Animals , Thrombopoietin/therapeutic use , Receptors, Fc/therapeutic use , Recombinant Fusion Proteins/therapeutic use , Recombinant Fusion Proteins/adverse effects , Recombinant Fusion Proteins/administration & dosage , Dog Diseases/drug therapy , Retrospective Studies , Female , Thrombocytopenia/veterinary , Thrombocytopenia/drug therapy , Male , Platelet Count/veterinary , Treatment Outcome , Purpura, Thrombocytopenic, Idiopathic/drug therapy , Purpura, Thrombocytopenic, Idiopathic/veterinaryABSTRACT
BACKGROUND: AURIGA is the largest prospective real-world study to evaluate intravitreal aflibercept 2â¯mg (IVT-AFL) treatment of macular edema (ME) secondary to retinal vein occlusion (RVO) and diabetic macular edema. Here we present the 24-month data from the German cohort of treatment-naïve patients with ME due to RVO. METHODS: Treatment-naïve patients with ME secondary to RVO were treated with IVT-AFL 2â¯mg in the routine clinical practice. The primary endpoint was mean change in visual acuity (VA, early treatment diabetic retinopathy, ETDRS, letters) at month 12 compared to baseline. Analyses were descriptive. RESULTS: Analysis included 130 patients with RVO (nâ¯= 61, 46.9% with central RVO, nâ¯= 69, 53.1% with branch RVO). The mean (± SD) time the RVO patients remained in the study was 18.4⯱ 7.4 months. The mean VA gain (95% confidence interval) in the overall cohort was +10.9 (7.5-14.2) letters at month 12 and +9.7 (6.1-13.3) at month 24 (baseline VA 56.5⯱ 18.9 letters). At 24 months, 67% of RVO patients gained ≥5 letters and 40% gained ≥15 letters. The mean number of injections was 4.4⯱ 1.3 up to month 6, 6.2⯱ 2.7 up to month 12 and 8.2⯱ 4.5 up to month 24. The mean central retinal thickness (CRT) reduction was -206µm (-252 to -160µm) at 12 months and -219µm (-263 to -175µm) at 24 months (baseline CRT 507⯱ 177⯵m). The safety profile was consistent with that of previous studies. DISCUSSION: In the German AURIGA cohort of treatment-naïve patients with ME secondary to RVO, IVT-AFL 2â¯mg treatment in clinical practice resulted in rapid and clinically relevant VA gains and a reduction in CRT. These results were largely maintained over 24 months despite the low injection frequency from month 6.
Subject(s)
Intravitreal Injections , Macular Edema , Receptors, Vascular Endothelial Growth Factor , Recombinant Fusion Proteins , Retinal Vein Occlusion , Visual Acuity , Receptors, Vascular Endothelial Growth Factor/administration & dosage , Receptors, Vascular Endothelial Growth Factor/therapeutic use , Humans , Recombinant Fusion Proteins/administration & dosage , Recombinant Fusion Proteins/therapeutic use , Recombinant Fusion Proteins/adverse effects , Retinal Vein Occlusion/drug therapy , Retinal Vein Occlusion/complications , Macular Edema/drug therapy , Male , Female , Aged , Germany , Visual Acuity/drug effects , Middle Aged , Prospective Studies , Treatment Outcome , Angiogenesis Inhibitors/therapeutic use , Angiogenesis Inhibitors/administration & dosage , Angiogenesis Inhibitors/adverse effects , Follow-Up Studies , Tomography, Optical CoherenceABSTRACT
To compare the efficacy and safety of the proposed aflibercept biosimilar SCD411 and reference aflibercept in patients with neovascular age-related macular degeneration, this randomized, double-masked, parallel-group, multicenter study was conducted in 14 countries from 13 August 2020 to 8 September 2022. Patients with neovascular age-related macular degeneration. With subfoveal, juxtafoveal, or extrafoveal choroidal neovascularization were aged 50 years or older. Intravitreal injection of SCD411 or aflibercept (2.0 mg) were administered every 4 weeks for the first three injections and every 8 weeks until week 48. The primary efficacy endpoint was the change in best-corrected visual acuity from baseline to week 8 with an adjusted equivalence margin of ± 3.0 letters. Patients were randomly assigned to receive either SCD411 (n = 288) or reference aflibercept (n = 288). A total of 566 participants (98.3%) completed week 8 of the study. The least-squares mean difference of change in best-corrected visual acuity from baseline to week 8 (SCD411-aflibercept) was - 0.4 letters (90% confidence interval = - 1.6 to 0.9). The incidence of ocular (69 of 287 [24.0%] vs. 71 of 286 [24.8%]) and serious ocular (5 of 287 [1.7%] vs. 3 of 286 [1.0%]) treatment-emergent adverse effects were similar between the SCD411 and aflibercept groups. Immunogenicity analysis revealed a low incidence of neutralizing antibody formation in both groups. In conclusion, SCD411 has equivalent efficacy compared with reference aflibercept in patients with neovascular age-related macular degeneration and has a comparable safety profile. The results support the potential use of SCD411 for the treatment of neovascular age-related macular degeneration.
Subject(s)
Intravitreal Injections , Receptors, Vascular Endothelial Growth Factor , Recombinant Fusion Proteins , Visual Acuity , Humans , Receptors, Vascular Endothelial Growth Factor/therapeutic use , Receptors, Vascular Endothelial Growth Factor/administration & dosage , Recombinant Fusion Proteins/adverse effects , Recombinant Fusion Proteins/therapeutic use , Recombinant Fusion Proteins/administration & dosage , Male , Female , Aged , Visual Acuity/drug effects , Treatment Outcome , Macular Degeneration/drug therapy , Middle Aged , Double-Blind Method , Aged, 80 and over , Choroidal Neovascularization/drug therapy , Biosimilar Pharmaceuticals/therapeutic use , Biosimilar Pharmaceuticals/adverse effects , Biosimilar Pharmaceuticals/administration & dosage , Angiogenesis Inhibitors/therapeutic use , Angiogenesis Inhibitors/adverse effects , Angiogenesis Inhibitors/administration & dosageABSTRACT
AIM: To compare the incidence of adverse events (AEs) related to antiobesity medications (AOMs; glucagon-like peptide-1 receptor agonists [GLP-1RAs] vs. non-GLP-1RAs) after bariatric surgery. METHODS: This single-centre retrospective cohort included patients (aged 16-65 years) who had undergone laparoscopic Roux-en-Y gastric bypass or sleeve gastrectomy (cohort entry date) and initiated AOMs. Participants were categorized as users of US Food and Drug Administration (FDA)-approved, off-label, or GLP-1RA AOMs if documented as receiving the medication on or after cohort entry date. Non-GLP-1RA AOMs were phentermine, orlistat, topiramate, canagliflozin, dapagliflozin, empagliflozin, naltrexone, bupropion/naltrexone and phentermine/topiramate. GLP-1RA AOMs included: semaglutide, dulaglutide, exenatide and liraglutide. The primary outcome was AE incidence. Logistic regression was used to determine the association of AOM exposure with AEs. RESULTS: We identified 599 patients meeting our inclusion criteria, 83% of whom were female. Their median (interquartile range [IQR]) age was 47.8 (40.9-55.4) years. The median duration of surgery to AOM exposure was 30 months. GLP-1RAs use was not associated with higher odds of AEs: adjusted odds ratio (aOR) 1.1 (95% confidence interval [CI] 0.5-2.6) and aOR 1.1 (95% CI 0.6-2.3) for GLP-1RA versus FDA-approved and off-label AOM use, respectively. AOM initiation ≥12 months after surgery was associated with lower risk of AEs compared to <12 months (aOR 0.01 [95% CI 0.0-0.01]; p < 0.001). CONCLUSION: Our results showed that GLP-1RA AOMs were not associated with an increased risk of AEs compared to non-GLP-1RA AOMs in patients who had previously undergone bariatric surgery. Prospective studies are needed to identify the optimal timeframe for GLP-1RA initiation.
Subject(s)
Anti-Obesity Agents , Bariatric Surgery , Glucagon-Like Peptide-1 Receptor , Humans , Female , Middle Aged , Adult , Male , Glucagon-Like Peptide-1 Receptor/agonists , Retrospective Studies , Anti-Obesity Agents/therapeutic use , Anti-Obesity Agents/adverse effects , Young Adult , Adolescent , Bariatric Surgery/adverse effects , Aged , Liraglutide/therapeutic use , Exenatide/therapeutic use , Obesity, Morbid/surgery , Glucagon-Like Peptides/therapeutic use , Glucagon-Like Peptides/analogs & derivatives , Glucagon-Like Peptides/adverse effects , Immunoglobulin Fc Fragments/therapeutic use , Immunoglobulin Fc Fragments/adverse effects , Recombinant Fusion Proteins/therapeutic use , Recombinant Fusion Proteins/adverse effects , Glucagon-Like Peptide-1 Receptor AgonistsSubject(s)
Recombinant Fusion Proteins , Humans , Recombinant Fusion Proteins/therapeutic use , Recombinant Fusion Proteins/adverse effects , Recombinant Fusion Proteins/administration & dosage , Hypertension, Pulmonary/drug therapy , Hypertension, Pulmonary/physiopathology , Pulmonary Arterial Hypertension/drug therapy , Pulmonary Arterial Hypertension/physiopathology , Antihypertensive Agents/adverse effects , Antihypertensive Agents/therapeutic use , Antihypertensive Agents/administration & dosage , Treatment OutcomeABSTRACT
Intravitreal injection (IVI) of anti-angiogenic drugs is one of the most common therapeutic procedures in ophthalmology. In recent years, a new non-contact study method has been developed - anterior segment optical coherence tomography (AS-OCT), which allows the formation of three-dimensional images of the lens and provides more detailed information about its structure and morphology. PURPOSE: This study uses optical coherence tomography method to analyze the risks of developing changes in the posterior lens capsule in patients after IVI of an anti-angiogenic drug. MATERIAL AND METHODS: The study involved 100 people (14 men and 86 women) with a natural lens and neovascular age-related macular degeneration (nAMD). The average age was 70.57±7.98 years. During the study (12 months), all patients underwent IVI of an anti-angiogenic drug aflibercept in the treat-and-extend (T&E) mode. All subjects were divided into 2 groups: with a total number of IVI less than 10 - group 1 (50 patients), and more than 10 IVI - group 2 (50 patients, of which 49 were included in the study). All patients underwent OCT using the Optopol REVO NX device (Poland) with the Anterior B-scan Wide protocol before inclusion in the study, as well as after 3, 6 and 12 months. RESULTS: It was found that the risk of developing a posterior lens capsule rupture, visualized using OCT, depends on the total number of IVI (correlation coefficient 0.473 p=0.001): the more IVI, the higher the probability that damage to the posterior capsule will occur after the next IVI, and after the 15th injection the risk of developing damage to the posterior capsule increases sharply. CONCLUSION: The astudy analyzed the risk factors for the development of posterior lens capsule damage that can be detected using OCT, and presented three risk groups for the development of rupture (or damage) of the posterior lens capsule depending on the number of intravitreal injections performed.
Subject(s)
Angiogenesis Inhibitors , Intravitreal Injections , Receptors, Vascular Endothelial Growth Factor , Recombinant Fusion Proteins , Tomography, Optical Coherence , Humans , Tomography, Optical Coherence/methods , Female , Male , Angiogenesis Inhibitors/administration & dosage , Angiogenesis Inhibitors/adverse effects , Aged , Receptors, Vascular Endothelial Growth Factor/administration & dosage , Recombinant Fusion Proteins/administration & dosage , Recombinant Fusion Proteins/adverse effects , Posterior Capsule of the Lens/diagnostic imaging , Posterior Capsule of the Lens/drug effects , Middle Aged , Macular Degeneration/drug therapy , Macular Degeneration/diagnosisABSTRACT
BACKGROUND: Macular retinoschisis (MRS) and myopic macular neovascularization (mMNV) are both potentially blinding complications of high myopia. In this case report, we highlight the progression of MRS after intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment for mMNV, as well as an extensive review of the literature on this topic. CASE DESCRIPTION: A 49-year-old woman presented with two weeks of recent onset blurring and metamorphopsia in her right eye. She had high myopia in both eyes (right eye - 20/60 with - 16D, left eye - 20/20 with - 13D). Slit-lamp ophthalmoscopy found a normal anterior segment in both eyes. On fundus examination, features of pathological myopia with posterior staphyloma and peripapillary atrophy were observed in both eyes. An active mMNV, as well as intraretinal fluid, minimal perifoveal inner and outer MRS, and focal posterior vitreous traction along the inferotemporal retinal arcade, were detected on optical coherence tomography (OCT) of the right eye. The patient received an intravitreal injection of Aflibercept (2 mg/0.05 ml). RESULTS: OCT scans at two- and four-month follow-up visits revealed regressed mMNV with a taut epiretinal membrane, progressive worsening of outer MRS, and the development of multiple perifoveal retinal detachment inferior to the fovea. Pars plana vitrectomy surgery was performed for the progressive MRS with good anatomical (resolved MRS) and functional outcome (maintained visual acuity at 20/60) at the last one-month post-surgery visit. CONCLUSION: Intravitreal anti-VEGF injections for mMNV can cause vitreoretinal interface changes, exacerbating MRS and causing visual deterioration. Vitrectomy for MRS could be one of several treatment options.
Subject(s)
Intravitreal Injections , Myopia, Degenerative , Receptors, Vascular Endothelial Growth Factor , Recombinant Fusion Proteins , Retinoschisis , Tomography, Optical Coherence , Visual Acuity , Humans , Receptors, Vascular Endothelial Growth Factor/therapeutic use , Receptors, Vascular Endothelial Growth Factor/antagonists & inhibitors , Receptors, Vascular Endothelial Growth Factor/administration & dosage , Female , Middle Aged , Retinoschisis/diagnosis , Recombinant Fusion Proteins/administration & dosage , Recombinant Fusion Proteins/adverse effects , Myopia, Degenerative/complications , Angiogenesis Inhibitors/adverse effects , Angiogenesis Inhibitors/administration & dosage , Disease Progression , Retinal Neovascularization/drug therapy , Retinal Neovascularization/diagnosis , Retinal Neovascularization/chemically induced , Fluorescein AngiographyABSTRACT
AIM: To assess the efficacy and safety of dulaglutide 1.5 mg versus dulaglutide 0.75 mg in Japanese participants with type 2 diabetes (T2D). MATERIALS AND METHODS: A Phase 3, multicentre, randomized, double-blind, parallel-group study was conducted in Japanese participants aged ≥20 years, with T2D for ≥6 months and inadequate glycaemic control, while on a single oral antihyperglycaemic medication (NCT04809220). The primary objective was to evaluate superiority of dulaglutide 1.5 mg versus dulaglutide 0.75 mg measured by mean change in glycated haemoglobin (HbA1c) from baseline to 26 weeks. Other efficacy and safety endpoints were evaluated at 26 and 52 weeks. All statistical analyses were conducted using the intention-to-treat population. RESULTS: Overall, 591 participants were randomized to once-weekly dulaglutide 1.5 mg or 0.75 mg. At Week 26, dulaglutide 1.5 mg was superior to dulaglutide 0.75 mg in HbA1c reduction from baseline (least squares mean [LSM] difference -0.29% [95% confidence interval {CI} -0.43, -0.14]). At Week 52, the dulaglutide 1.5-mg arm had a significantly greater proportion of participants who achieved HbA1c <7.0% (46.3% vs. 38.5%; p = 0.03) and showed significantly greater reduction in fasting serum glucose (LSM difference -9.4 mg/dL [95% CI -14.4, -4.3]; p < 0.001) versus the dulaglutide 0.75-mg arm. No statistically significant change in body weight was observed in either treatment arm. Overall, 442 participants (75.4%) experienced treatment emergent adverse events (TEAEs). Constipation (11.3%), diarrhoea (9.6%) and pyrexia (9.0%) were the most commonly reported TEAEs. CONCLUSIONS: Dulaglutide 1.5 mg once weekly demonstrated superior glycaemic control versus dulaglutide 0.75 mg once weekly, with comparable safety and tolerability, in Japanese people with T2D.
Subject(s)
Blood Glucose , Diabetes Mellitus, Type 2 , Glucagon-Like Peptides , Glycated Hemoglobin , Hypoglycemic Agents , Immunoglobulin Fc Fragments , Recombinant Fusion Proteins , Humans , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/blood , Recombinant Fusion Proteins/administration & dosage , Recombinant Fusion Proteins/adverse effects , Recombinant Fusion Proteins/therapeutic use , Immunoglobulin Fc Fragments/adverse effects , Immunoglobulin Fc Fragments/administration & dosage , Immunoglobulin Fc Fragments/therapeutic use , Glucagon-Like Peptides/analogs & derivatives , Glucagon-Like Peptides/administration & dosage , Glucagon-Like Peptides/adverse effects , Glucagon-Like Peptides/therapeutic use , Male , Middle Aged , Female , Double-Blind Method , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/adverse effects , Hypoglycemic Agents/therapeutic use , Glycated Hemoglobin/metabolism , Glycated Hemoglobin/analysis , Japan , Aged , Blood Glucose/drug effects , Blood Glucose/metabolism , Treatment Outcome , Adult , Hypoglycemia/chemically induced , Hypoglycemia/epidemiology , Drug Administration Schedule , East Asian PeopleABSTRACT
PURPOSE: This study compares the changes in the parameters of the anterior chamber of the eye using anterior segment optical coherence tomography (AS-OCT) in patients with a natural and artificial lens after treatment of neovascular age-related macular degeneration (nAMD) by multiple intravitreal injections (IVI) of anti-VEGF drugs. MATERIAL AND METHODS: The patients were divided into 2 groups: group 1 (control) included 30 patients (30 eyes) with a natural lens, group 2 - 30 patients (30 eyes) with an intraocular lens (IOL). AS-OCT was performed using the Revo NX tomograph (Optopol, Poland) to analyze anterior chamber depth (ACD) and the parameters of anterior chamber angle (ACA). Intraocular pressure (IOP) was measured with a contact tonometer ICare Pro. RESULTS: In patients with an IOL, the IOP level 1 minute after intravitreal injection (IVI) of an anti-VEGF drug was statistically lower than in the control group, on average by 17.8% during the first IVI and by 28.7% after 1 year of observation (p<0.001). ACD before treatment was statistically significantly higher in patients with IOL compared to patients of group 1 by an average of 39.3% (p<0.001). ACA from the nasal and temporal sides in the meridian 0°-180° before the start of treatment was statistically significantly wider in phakic patients than in the control group, by an average of 15.9±9.3° (p<0.001) and 16.9±8.2° (p<0.001), respectively. According to AS-OCT, there was no shift of the iris-lens diaphragm in patients with an IOL after multiple IVI of an anti-VEGF drug, in contrast to the control group. CONCLUSIONS: AS-OCT was used to determine for the first time the changes in the parameters of the anterior chamber of the eye in patients with a natural and artificial lens after multiple injections of an anti-VEGF drug in the treatment of nAMD.
Subject(s)
Angiogenesis Inhibitors , Anterior Eye Segment , Intraocular Pressure , Lens, Crystalline , Lenses, Intraocular , Macular Degeneration , Receptors, Vascular Endothelial Growth Factor , Recombinant Fusion Proteins , Vascular Endothelial Growth Factor A , Intraocular Pressure/drug effects , Anterior Eye Segment/diagnostic imaging , Anterior Eye Segment/drug effects , Intravitreal Injections , Tomography, Optical Coherence , Macular Degeneration/drug therapy , Humans , Male , Female , Middle Aged , Aged , Recombinant Fusion Proteins/administration & dosage , Recombinant Fusion Proteins/adverse effects , Receptors, Vascular Endothelial Growth Factor/administration & dosage , Receptors, Vascular Endothelial Growth Factor/antagonists & inhibitors , Angiogenesis Inhibitors/administration & dosage , Angiogenesis Inhibitors/adverse effects , Vascular Endothelial Growth Factor A/antagonists & inhibitorsABSTRACT
OBJECTIVES: Induction treatment in renal transplant is associated with better graft survival. However, intensified immunosuppression is known to cause unwanted side effects such as infection and malignancy. Furthermore, the effects of the routine use of immunosuppressants in low-risk kidney transplant recipients are still not clear. In this study, we assessed the first-year safety and efficacy of induction treatment. MATERIALS AND METHODS: We examined first living donor kidney transplant patients who were on tacrolimus based immunosuppression therapy. We formed 3 groups according to the induction status: antithymocyte globulin induction, basiliximab induction, and no induction. We collected outcome data on delayed graft function, graft loss, creatinine levels, estimated glomerular filtration rates, acute rejection episodes, hospitalization episodes, and infection episodes, including cytomegalovirus infection and bacterial infections. RESULTS: We examined a total of 126 patients (age 35 ± 12 years; 65% male). Of them, 25 received antithymocyte globulin, 52 received basiliximab, and 49 did notreceive any induction treatment. We did not observe any statistically significant difference among the 3 groups in terms of acute rejection episodes, delayed graft function, and first-year graft loss. The estimated glomerular filtration rates were similar among the groups. Overall bacterial infectious complications and cytomegalovirus infection showed similar prevalence among all groups. Hospitalization was less common in the induction-free group. CONCLUSIONS: In low-risk patients, induction-free regimens could be associated with a better safety profile without compromising graft survival. Therefore, induction treatment may be disregarded in first living donor transplant patients who receive tacrolimusbased triple immunosuppression treatment.
Subject(s)
Antilymphocyte Serum , Basiliximab , Immunosuppressive Agents , Kidney Transplantation , Living Donors , Tacrolimus , Adult , Female , Humans , Male , Middle Aged , Young Adult , Antilymphocyte Serum/adverse effects , Antilymphocyte Serum/therapeutic use , Basiliximab/adverse effects , Basiliximab/therapeutic use , Calcineurin Inhibitors/adverse effects , Calcineurin Inhibitors/administration & dosage , Delayed Graft Function/immunology , Drug Therapy, Combination , Graft Rejection/immunology , Graft Rejection/prevention & control , Graft Survival/drug effects , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use , Kidney Transplantation/adverse effects , Recombinant Fusion Proteins/adverse effects , Recombinant Fusion Proteins/therapeutic use , Retrospective Studies , Risk Factors , Tacrolimus/adverse effects , Tacrolimus/therapeutic use , Time Factors , Treatment OutcomeABSTRACT
Olamkicept selectively inhibits the cytokine interleukin-6 (IL-6) trans-signaling pathway without blocking the classic pathway and is a promising immunoregulatory therapy for inflammatory bowel disease (IBD). These first-in-human, randomized, placebo-controlled, single- (SAD) and multiple-ascending dose (MAD) trials evaluated olamkicept safety, tolerability, pharmacokinetic, and pharmacodynamic characteristics. Doses tested in the SAD trial included seven single intravenous doses (0.75, 7.5, 75, 150, 300, 600, and 750 mg) and one subcutaneous (SC) dose (60 mg) given to healthy subjects (N = 64), and three intravenous doses (75 mg, 300 mg, and 750 mg) given to patients with Crohn's disease (CD; N = 24). Doses tested in the MAD trial included multiple intravenous doses (75, 300, and 600 mg once weekly for 4 weeks) given to healthy subjects (N = 24). No severe or serious treatment-emergent adverse events (TEAEs) were recorded. The most common TEAEs were headache, nasopharyngitis, and myalgia in the SAD trial, and diarrhea, headache, and cough in the MAD trial. Infusion-related reactions occurred in one and two subjects in the SAD and MAD trial, respectively, leading to treatment discontinuation in the MAD trial. Olamkicept showed dose-independent pharmacokinetics after single and multiple administrations, and there was no major difference in systemic exposure between healthy subjects and patients with CD. Complete target engagement (inhibition of phosphorylation of signal transducer and activator of transcription-3) was achieved in blood around or above olamkicept serum concentrations of 1-5 µg/mL. Overall, these results suggest that olamkicept is safe and well-tolerated in healthy subjects and patients with CD after single intravenous/SC and multiple intravenous administrations.
Subject(s)
Crohn Disease , Dose-Response Relationship, Drug , Humans , Male , Female , Adult , Crohn Disease/drug therapy , Crohn Disease/immunology , Middle Aged , Young Adult , Double-Blind Method , Recombinant Fusion Proteins/pharmacokinetics , Recombinant Fusion Proteins/administration & dosage , Recombinant Fusion Proteins/adverse effects , Injections, Subcutaneous , Drug Administration Schedule , Interleukin-6/blood , Healthy Volunteers , AdolescentABSTRACT
The use of dulaglutide, a common medication for managing type 2 diabetes, rarely causes elevated pancreatic tumour markers. Here, we report the case of a woman in her mid-60s with diabetes for over 10 years. The patient presented with markedly elevated serum CA19-9 and CA242 levels revealed during a routine health examination despite being asymptomatic. She had been receiving dulaglutide injections for 16 months. Imaging and interventional assessments did not reveal any hepatobiliary, gastrointestinal or pancreatic neoplasm. After excluding alternate diagnoses, the patient was determined to exhibit an adverse reaction to dulaglutide use. Management involved the discontinuation of dulaglutide, which resulted in normalisation of serum CA19-9 and CA242 levels within 6 weeks. This case underscores the importance of discontinuing dulaglutide and monitoring changes in the biomarker levels in asymptomatic patients receiving dulaglutide, rather than immediately resorting to imaging and endoscopic examinations.
Subject(s)
CA-19-9 Antigen , Diabetes Mellitus, Type 2 , Glucagon-Like Peptides , Hypoglycemic Agents , Immunoglobulin Fc Fragments , Recombinant Fusion Proteins , Humans , Recombinant Fusion Proteins/adverse effects , Recombinant Fusion Proteins/therapeutic use , Recombinant Fusion Proteins/administration & dosage , Glucagon-Like Peptides/analogs & derivatives , Glucagon-Like Peptides/adverse effects , Glucagon-Like Peptides/therapeutic use , Female , Immunoglobulin Fc Fragments/adverse effects , Immunoglobulin Fc Fragments/therapeutic use , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/blood , CA-19-9 Antigen/blood , Middle Aged , Hypoglycemic Agents/adverse effects , Hypoglycemic Agents/therapeutic use , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/bloodABSTRACT
PURPOSE: In this study, we report the results from the esophageal squamous cell carcinoma (SCC) cohort of a phase II, noncomparative, basket study evaluating the antitumor activity and safety of fibroblast activation protein-IL2 variant (FAP-IL2v) plus atezolizumab in patients with advanced/metastatic solid tumors (NCT03386721). PATIENTS AND METHODS: Eligible patients had an Eastern Cooperative Oncology Group performance status of 0 to 1; measurable metastatic, persistent, or recurrent esophageal SCC; progression on ≥1 prior therapy; and were checkpoint inhibitor-naïve. Patients received FAP-IL2v 10 mg plus atezolizumab 1,200 mg intravenously every 3 weeks, or FAP-IL2v weekly for 4 weeks and then every 2 weeks plus atezolizumab 840 mg intravenously every 2 weeks. The primary endpoint was investigator-assessed objective response rate (ORR). RESULTS: In the response-evaluable population (N = 34), the best confirmed ORR was 20.6% [95% confidence interval (CI), 10.4-36.8], with a complete response seen in 1 patient and partial responses in 6 patients. The disease control rate was 44.1% (complete response = 2.9%; partial response = 17.6%; stable disease = 23.5%), and the median duration of response was 10.1 mon/ths (95% CI, 5.6-26.7). The median progression-free survival was 1.9 months (95% CI, 1.8-3.7). Analysis of response by PDL1 expression (Ventana SP263) resulted in an ORR of 26.7% for patients with PDL1-positive tumors (tumor area positivity cutoff ≥1%; n = 15) and 7.1% for patients with PDL1-negative tumors (tumor area positivity cutoff <1%; n = 14). Overall, the treatment combination was tolerable, and adverse events were consistent with the known safety profiles of each drug. CONCLUSIONS: FAP-IL2v plus atezolizumab demonstrated clinical activity and was tolerable in patients with previously treated esophageal SCC.
Subject(s)
Antibodies, Monoclonal, Humanized , Antineoplastic Combined Chemotherapy Protocols , Esophageal Neoplasms , Humans , Female , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/adverse effects , Male , Middle Aged , Aged , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/pathology , Esophageal Neoplasms/genetics , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Adult , Aged, 80 and over , Esophageal Squamous Cell Carcinoma/drug therapy , Esophageal Squamous Cell Carcinoma/genetics , Esophageal Squamous Cell Carcinoma/pathology , Endopeptidases/genetics , Membrane Proteins/genetics , Gelatinases/genetics , Recombinant Fusion Proteins/administration & dosage , Recombinant Fusion Proteins/adverse effectsABSTRACT
OBJECTIVE: This prospective study aimed to describe the clinical course in terms of glycemic outcomes, body weight, and adverse events during the first 12 weeks following a switch from glucagon-like peptide-1 receptor agonists (GLP-1 RAs) directly to tirzepatide 5 mg. METHODS: Participants were ≥18 years with type 2 diabetes (T2D), glycated hemoglobin (HbA1c) ≥6.5% to ≤9.0%, body mass index ≥25 kg/m2 and were on a stable treatment dose of GLP-1 RAs (liraglutide every day [1.2, 1.8 mg], semaglutide once-weekly [0.5, 1.0, 2.0 mg], or dulaglutide once-weekly [0.75, 1.5, 3.0, and 4.5 mg]) for ≥3 months at baseline. The primary end point was HbA1c change from baseline at week 12. Secondary end points included change from baseline in fasting serum glucose, body weight, and glucose assessed by continuous glucose monitoring. Safety was also assessed. RESULTS: Participants were 58.3 years on average, with baseline HbA1c 7.39%, body mass index 35.18 kg/m2, T2D duration around 12.4 years, and included 55% females. Semaglutide (55%) and dulaglutide (42%) were the most commonly used GLP-1 RAs at baseline with semaglutide 1.0 mg and dulaglutide 1.5 mg being the most common treatment doses. At week 12, mean HbA1c changed from baseline by -0.43%, fasting serum glucose by -7.83 mg/dL, and body weight by -2.15 kg (all P < .01). Glycemic outcomes and body weight improved in participants in all baseline GLP-1 RA subgroups. Twenty participants (13.2%) developed gastrointestinal events. Three (2%) participants discontinued tirzepatide due to adverse events. There were no severe hypoglycemic events or deaths. CONCLUSION: In this prospective study, when people with T2D on stable GLP-1 RA treatment were switched directly to tirzepatide 5 mg, they experienced improved glycemic outcomes and additional weight reduction with an acceptable risk of adverse gastrointestinal events over 12 weeks.
Subject(s)
Blood Glucose , Diabetes Mellitus, Type 2 , Glucagon-Like Peptide-1 Receptor Agonists , Glucagon-Like Peptides , Hypoglycemic Agents , Immunoglobulin Fc Fragments , Adult , Aged , Female , Humans , Male , Middle Aged , Blood Glucose/drug effects , Blood Glucose/analysis , Body Weight/drug effects , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/blood , Drug Substitution , Gastric Inhibitory Polypeptide , Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage , Glucagon-Like Peptide-1 Receptor Agonists/adverse effects , Glucagon-Like Peptide-2 Receptor , Glucagon-Like Peptides/analogs & derivatives , Glucagon-Like Peptides/administration & dosage , Glucagon-Like Peptides/therapeutic use , Glucagon-Like Peptides/adverse effects , Glycated Hemoglobin/analysis , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/therapeutic use , Hypoglycemic Agents/adverse effects , Immunoglobulin Fc Fragments/administration & dosage , Immunoglobulin Fc Fragments/therapeutic use , Immunoglobulin Fc Fragments/adverse effects , Liraglutide/administration & dosage , Liraglutide/therapeutic use , Liraglutide/adverse effects , Prospective Studies , Recombinant Fusion Proteins/administration & dosage , Recombinant Fusion Proteins/therapeutic use , Recombinant Fusion Proteins/adverse effectsABSTRACT
Thrombopoietin receptor agonists (TPO-RAs) induce trilineage hematopoiesis under conditions with acquired hematopoietic failure. We evaluated safety, tolerability, and preliminary efficacy of a TPO-RA, romiplostim (Nplate), with or without standard-of-care immunosuppressive therapy (±IST) for children (ages < 21 y) with newly diagnosed and relapsed/refractory severe aplastic anemia (SAA) and myelodysplastic syndrome (MDS). Data were collected from an observational study and a single arm interventional pilot study. The safety outcome was treatment-related adverse events (AEs). Efficacy was evaluated by complete hematopoietic response (CHR) at week 24. Romiplostim was commenced at 5 µg/kg/week, with dose escalation of 2.5 µg/kg/week (maximum, 20 µg/kg/dose) based on platelet response. Romiplostim was continued until CHR was observed. Ten subjects (SAA, 9 [IST, 4; without IST, 5]; MDS, 1) completed the study (median age: 9.2 y). Median romiplostim dose was 10 µg/kg/week (range: 5 to 17.5 µg/kg/week). The cumulative incidence of CHR was 70.4% (95% CI, 20.2%-92.6%). Among 21 AEs (Grade 1 to 3), 3 were attributed to romiplostim. At a median posttherapy follow-up of 10.9 months (range: 0.7 to 77.5), no clonal evolution, bone marrow fibrosis or mortality was reported. This proof-of-concept study provides data about short-term safety, tolerability, and preliminary efficacy of romiplostim (±IST) for treatment of pediatric SAA/MDS.
Subject(s)
Anemia, Aplastic , Myelodysplastic Syndromes , Receptors, Fc , Recombinant Fusion Proteins , Thrombopoietin , Humans , Recombinant Fusion Proteins/therapeutic use , Recombinant Fusion Proteins/administration & dosage , Recombinant Fusion Proteins/adverse effects , Receptors, Fc/therapeutic use , Receptors, Fc/administration & dosage , Anemia, Aplastic/drug therapy , Thrombopoietin/therapeutic use , Thrombopoietin/adverse effects , Thrombopoietin/administration & dosage , Myelodysplastic Syndromes/drug therapy , Myelodysplastic Syndromes/pathology , Child , Female , Adolescent , Male , Young Adult , Child, Preschool , Pilot Projects , Adult , Receptors, Thrombopoietin/agonistsABSTRACT
Importance: Prospective long-term data after retinopathy of prematurity (ROP) treatment with anti-vascular endothelial growth factor injections vs laser therapy are scarce. The FIREFLEYE (Aflibercept for ROP IVT Injection vs Laser Therapy) next trial is prospectively evaluating the long-term efficacy and safety outcomes following ROP treatment with intravitreal aflibercept vs laser therapy. Objective: To evaluate 2-year ophthalmic and safety outcomes after 0.4-mg aflibercept injection or laser therapy in the 24-week randomized (2:1) FIREFLEYE trial (FIREFLEYE outcomes previously reported). Design, Setting, and Participants: This prospective nonrandomized controlled trial performed in 24 countries in Asia, Europe, and South America (2020-2025) follows up participants treated in the FIREFLEYE randomized clinical trial (2019-2021) through 5 years of age. Participants included children born very or extremely preterm (gestational age ≤32 weeks) or with very or extremely low birth weight (≤1500 g) who were previously treated with a 0.4-mg injection of aflibercept compared with laser therapy for severe acute-phase ROP. Data for the present interim analysis were acquired from March 18, 2020, to July 25, 2022. Interventions: Complications of ROP treated at investigator discretion (no study treatment). Main Outcomes and Measures: Efficacy end points included ROP status, unfavorable structural outcomes, ROP recurrence, treatment for ROP complications, completion of vascularization, and visual function. Safety end points included adverse events and growth and neurodevelopmental outcomes. Results: Overall, 100 children were enrolled (median gestational age, 26 [range, 23-31] weeks; 53 boys and 47 girls). Of these, 21 were Asian, 2 were Black, 75 were White, and 2 were of more than 1 race. At 2 years of age, 61 of 63 children (96.8%) in the aflibercept group vs 30 of 32 (93.8%) in the laser group had no ROP. Through 2 years of age, 62 of 66 (93.9%) in the aflibercept group and 32 of 34 (94.1%) in the laser group had no unfavorable structural outcomes. No new retinal detachment occurred during the study. Four children in the aflibercept group (6.1%) were treated for ROP complications before 1 year of age (2 had preexisting end-stage disease and total retinal detachment; 1 had reactivated plus disease; and 1 had recurrent retinal neovascularization not further specified). Most children were able to fix and follow a 5-cm toy (aflibercept group, 118 of 122 eyes [96.7%] among 63 children; laser group, 62 of 63 eyes [98.4%] among 33 children). High myopia was present in 9 of 115 eyes (7.8%) among 5 children in the aflibercept group and 13 of 60 eyes (21.7%) among 9 children in the laser group. No relevant differences in growth and neurodevelopmental outcomes by Bayley Scales of Infant and Toddler Development, Third Edition and Vineland Adaptive Behavior Scales, Second Edition were identified. Conclusions and Relevance: In this nonrandomized follow-up of a randomized clinical trial comparing treatment of severe acute-phase ROP with 0.4-mg injection of aflibercept and laser, disease control was stable and visual function was appropriate in children through 2 years of age. No adverse effects on safety, including growth and neurodevelopment, were identified. These findings provide clinically relevant long-term information on intravitreal aflibercept injection therapy for ROP. Trial Registration: ClinicalTrials.gov Identifier: NCT04015180.
Subject(s)
Angiogenesis Inhibitors , Intravitreal Injections , Receptors, Vascular Endothelial Growth Factor , Recombinant Fusion Proteins , Retinopathy of Prematurity , Humans , Retinopathy of Prematurity/surgery , Retinopathy of Prematurity/therapy , Retinopathy of Prematurity/drug therapy , Receptors, Vascular Endothelial Growth Factor/therapeutic use , Recombinant Fusion Proteins/therapeutic use , Recombinant Fusion Proteins/adverse effects , Recombinant Fusion Proteins/administration & dosage , Female , Male , Infant, Newborn , Prospective Studies , Treatment Outcome , Angiogenesis Inhibitors/therapeutic use , Angiogenesis Inhibitors/adverse effects , Laser Therapy/methods , Laser Therapy/adverse effects , Infant , Child, PreschoolABSTRACT
This study aimed to evaluate the pharmacokinetics (PKs), safety, and immunogenicity of the biosimilar HEC14028 compared to reference Trulicity® (dulaglutide) in healthy male Chinese subjects. This study was a single-center, randomized, open, single-dose, parallel-controlled comparative Phase I clinical trial, including a screening period of up to 14 days, a 17-day observation period after administration, and a 7-day safety follow-up period. A total of 68 healthy male subjects were randomly assigned (1:1) to the test group (HEC14028) and the reference group (dulaglutide) (single 0.75 mg abdominal subcutaneous dose). The primary objective was to evaluate the pharmacokinetic characteristics of HEC14028 and compare the pharmacokinetic similarities between HEC14028 and dulaglutide. The primary PK endpoints were maximum plasma concentration (Cmax) and area under the blood concentration-time curve from zero time to the estimated infinite time (AUC0-∞). The study results showed that HEC14028 and dulaglutide were pharmacokinetically equivalent: 90% confidence interval (CI) of Cmax and AUC0-∞ geometric mean ratios were 102.9%-122.0% and 97.1%-116.9%, respectively, which were both within the range of 80.00%-125.00%. No grade 3 or above treatment emergent adverse events (TEAEs), serious adverse events (SAEs), TEAEs leading to withdrawal from the trial, or TEAEs leading to death were reported in this study. Both HEC14028 and dulaglutide showed good and similar safety profiles, and no incremental immunogenicity was observed in subjects receiving HEC14028 and dulaglutide.
Subject(s)
Biosimilar Pharmaceuticals , Glucagon-Like Peptides , Healthy Volunteers , Immunoglobulin Fc Fragments , Recombinant Fusion Proteins , Adolescent , Adult , Humans , Male , Middle Aged , Young Adult , Area Under Curve , Asian People , Biosimilar Pharmaceuticals/pharmacokinetics , Biosimilar Pharmaceuticals/administration & dosage , Biosimilar Pharmaceuticals/adverse effects , China , East Asian People , Glucagon-Like Peptides/pharmacokinetics , Glucagon-Like Peptides/analogs & derivatives , Glucagon-Like Peptides/administration & dosage , Glucagon-Like Peptides/adverse effects , Hypoglycemic Agents/pharmacokinetics , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/adverse effects , Immunoglobulin Fc Fragments/administration & dosage , Immunoglobulin Fc Fragments/adverse effects , Immunoglobulin Fc Fragments/immunology , Injections, Subcutaneous , Recombinant Fusion Proteins/pharmacokinetics , Recombinant Fusion Proteins/administration & dosage , Recombinant Fusion Proteins/adverse effects , Therapeutic EquivalencyABSTRACT
PURPOSE: Simlukafusp alfa [fibroblast activation protein α-targeted IL2 variant (FAP-IL2v)], a tumor-targeted immunocytokine, comprising an IL2 variant moiety with abolished CD25 binding fused to human IgG1, is directed against fibroblast activation protein α. This phase I, open-label, multicenter, dose-escalation, and extension study (NCT02627274) evaluated the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of FAP-IL2v in patients with advanced/metastatic solid tumors. PATIENTS AND METHODS: Participants received FAP-IL2v intravenously once weekly. Dose escalation started at 5 mg; flat dosing (≤25 mg) and intraparticipant uptitration regimens (15/20, 20/25, 20/20/35, and 20/35/35 mg) were evaluated. Primary objectives were dose-limiting toxicities, maximum tolerated dose, recommended expansion dose, and pharmacokinetics. RESULTS: Sixty-one participants were enrolled. Dose-limiting toxicities included fatigue (flat dose 20 mg: n = 1), asthenia (25 mg: n = 1), drug-induced liver injury (uptitration regimen 20/25 mg: n = 1), transaminase increase (20/25 mg: n = 1), and pneumonia (20/35/35 mg: n = 1). The uptitration regimen 15/20 mg was determined as the maximum tolerated dose and was selected as the recommended expansion dose. Increases in peripheral blood absolute immune cell counts were seen for all tested doses [NK cells, 13-fold; CD4+ T cells (including regulatory T cells), 2-fold; CD8+ T cells, 3.5-fold] but without any percentage change in regulatory T cells. Clinical activity was observed from 5 mg [objective response rate, 5.1% (n = 3); disease control rate, 27.1% (n = 16)]. Responses were durable [n = 3, 2.8 (censored), 6.3, and 43.4 months]. CONCLUSIONS: FAP-IL2v had a manageable safety profile and showed initial signs of antitumor activity in advanced/metastatic solid tumors.
Subject(s)
Maximum Tolerated Dose , Neoplasms , Humans , Female , Male , Neoplasms/drug therapy , Neoplasms/pathology , Neoplasms/genetics , Middle Aged , Aged , Adult , Interleukin-2/administration & dosage , Interleukin-2/adverse effects , Interleukin-2/pharmacokinetics , Interleukin-2/genetics , Neoplasm Metastasis , Recombinant Fusion Proteins/pharmacokinetics , Recombinant Fusion Proteins/administration & dosage , Recombinant Fusion Proteins/adverse effects , Recombinant Fusion Proteins/therapeutic use , Treatment Outcome , Endopeptidases/administration & dosage , Membrane ProteinsABSTRACT
BACKGROUND: Rilonacept, a once-weekly interleukin-1 alpha and beta cytokine trap, reduced pericarditis recurrence in the phase 3 study, RHAPSODY (Rilonacept Inhibition of Interleukin-1 Alpha and Beta for Recurrent Pericarditis: A Pivotal Symptomatology and Outcomes Study). The RHAPSODY long-term extension further explored recurrent pericarditis natural history and treatment duration decision-making during 24 additional months of open-label rilonacept treatment. METHODS AND RESULTS: Seventy-four patients commenced the long-term extension, with a median (maximum) total rilonacept duration of 22 (35) months. Individually, 18 months after the most proximal pericarditis recurrence, investigators decided to continue rilonacept on study, suspend rilonacept for off-treatment observation (rescue allowed), or discontinue the study. The annualized incidence of pericarditis recurrence on rilonacept up to the 18-month decision milestone was 0.04 events/patient-year versus 4.4 events/patient-year prestudy while on oral therapies. At the 18-month decision milestone, 64% (33/52) continued rilonacept, 15% (8/52) suspended rilonacept for observation, and 21% (11/52) discontinued the study. Among the 33 patients (1/33; 3.0%) continuing rilonacept (median time to recurrence could not be estimated due to too few events), a single recurrence occurred 4 weeks after a treatment interruption. Among patients suspending rilonacept, 75% (6/8) experienced recurrence (median time to recurrence, 11.8 weeks [95% CI, 3.7 weeks to not estimable]). There was a 98% reduction in risk of pericarditis recurrence among patients continuing rilonacept treatment after the 18-month decision milestone versus those suspending treatment for observation (hazard ratio, 0.02; P<0.0001). CONCLUSIONS: In the RHAPSODY long-term extension, continued rilonacept treatment resulted in continued response; treatment suspension at the 18-month decision milestone was associated with pericarditis recurrence. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03737110.