- |||||||||| Krystexxa (pegloticase) / Amgen
Trial primary completion date: PROTECT: Study of Pegloticase in Participants With Uncontrolled Gout Who Have Had a Kidney Transplant (clinicaltrials.gov) - Aug 18, 2021
P4, N=20, Active, not recruiting,
Chronic refractory gout patients not achieving protocol-defined persistent urate lowering still achieve significant clinical benefits with pegloticase treatment, suggesting that transient reduction in serum urate may result in sustained clinical benefit. Trial primary completion date: Jun 2021 --> Sep 2021
- |||||||||| Krystexxa (pegloticase) / Amgen
Trial completion date, Trial primary completion date: ULTRA-T2D: Uric Acid Lowering Trial in Youth Onset T2D (clinicaltrials.gov) - Aug 18, 2021
P2, N=10, Recruiting,
Trial primary completion date: Jun 2021 --> Sep 2021 Trial completion date: Dec 2022 --> Dec 2023 | Trial primary completion date: May 2022 --> May 2023
- |||||||||| Krystexxa (pegloticase) / Horizon Therapeutics
[VIRTUAL] Engineering polynorbornene based uricase conjugates for gout therapy (Room: Virtual Room) - Aug 13, 2021 - Abstract #ACSFall2021ACS_Fall_5215;
Therefore, PEGylated version of uricase enzyme, used for the treatment of gout called Pegloticase was met with 38% of patients eliciting anti-PEG antibodies in Phase I and 89% patients in the Phase III trials leading to a loss of treatment response, increased drug clearance, and risk of infusion reactions and adverse events in at least 90% of the patients.So evidently, the presence of anti-PEG antibodies could potentially lead to a loss of treatment response and adverse reactions in any PEG-based therapeutics and thus demands us to engineer an alternative for PEG...The uricase enzyme was modified by random conjugation mediated by lysine residues. The conjugates were purified by FPLC and ELISA test will be done for immunogenicity studies.Scheme 1: Synthesis of Uricase conjugates
- |||||||||| Krystexxa (pegloticase) / Horizon Therapeutics, Kineret (anakinra) / SOBI, Ilaris (canakinumab) / Novartis
Clinical, Review, Journal: Pharmacologic Management of Gout in Patients with Cardiovascular Disease and Heart Failure. (Pubmed Central) - Aug 1, 2021
An increased risk of cardiovascular death and HF hospitalization limit the use of febuxostat and pegloticase as ULT in this population. Ultimately, the selection of agents used for acute gout management and long-term ULT should be individualized according to patient and agent cardiovascular risk factors.
- |||||||||| Zurampic (lesinurad) / AstraZeneca, Krystexxa (pegloticase) / Horizon Therapeutics
Review, Journal: Changing paradigms in the management of gout. (Pubmed Central) - Jul 30, 2021
Advances in understanding the physiology and genetic control of urate transport in the kidney and gut have led to novel, more selective uricosuric drugs, and basic research on mediators of urate crystal-induced inflammation has pointed to alternative therapeutic targets for treating and preventing gout flares. Current guidelines for the management of gout and indications for the use of some more recently introduced drugs; febuxostat, lesinurad, pegloticase and interleukin-1 antagonists are also briefly reviewed.
- |||||||||| Krystexxa (pegloticase) / Horizon Therapeutics
Review, Journal: Therapeutic approaches in the treatment of gout. (Pubmed Central) - Jun 30, 2021
These, and other advances, have shaped our current strategies for managing gout. Here, we review the most current, evidence-based gout management approaches, including treating acute flares, addressing gout through the long-term regulation of serum urate, and prophylaxis against gouty flares during urate lowering.
- |||||||||| Krystexxa (pegloticase) / Horizon Therapeutics
Clinical, Review, Journal: Pegloticase treatment of chronic refractory gout: Update on efficacy and safety. (Pubmed Central) - Jun 30, 2021
However, these reactions can be avoided by stopping pegloticase when there is a loss of serum urate lowering. New dosing regimens and co-administration of immunosuppressive agents are also being employed to overcome this limitation and extend the benefits of pegloticase to a larger number of patients.
- |||||||||| Krystexxa (pegloticase) / Horizon Therapeutics
Journal: Development of a multivariable improvement measure for gout. (Pubmed Central) - Jun 22, 2021
New dosing regimens and co-administration of immunosuppressive agents are also being employed to overcome this limitation and extend the benefits of pegloticase to a larger number of patients. GMIM captures changes in disease activity in response to treatment with pegloticase and may serve as an evidence-based tool for assessment of responses to other urate-lowering therapies in gout patients.
- |||||||||| Krystexxa (pegloticase) / Horizon Therapeutics
[VIRTUAL] PHARMACOKINETICS OF PEGLOTICASE AND METHOTREXATE POLYGLUTAMATE(S) IN PATIENTS WITH UNCONTROLLED GOUT RECEIVING PEGLOTICASE AND CO-TREATMENT OF METHOTREXATE (Posters Viewing) - May 21, 2021 - Abstract #EULAR2021EULAR_2415;
Pegloticase 8 mg IV every 2 weeks co-treatment with MTX 15 mg weekly resulted in fewer patients with pegloticase C min below the quantification limit (BQL) and gave higher overall trough concentrations (C min ) compared to pegloticase monotherapy in the phase 3 studies. Pegloticase 8 mg IV every 2 weeks co-treatment with MTX 15 mg weekly was associated with an improved response rate for pegloticase in association with improved drug levels in these patients with uncontrolled gout compared to pegloticase monotherapy in the phase 3 studies.
- |||||||||| Krystexxa (pegloticase) / Horizon Therapeutics
[VIRTUAL] PRELIMINARY FINDINGS OF THE PROTECT CLINICAL TRIAL: PEGLOTICASE EFFICACY AND SAFETY IN KIDNEY TRANSPLANT RECIPIENTS (Posters Viewing) - May 21, 2021 - Abstract #EULAR2021EULAR_2400;
P4
Initial findings suggest that pegloticase therapy is effective at reducing sUA in most KT recipients while preserving renal function. Results suggest that in the setting of profound urate lowering with pegloticase in KT patients, eGFR remains stable and patients experience clinically beneficial reductions in pain and disability with an absence of unexpected safety findings.
- |||||||||| Krystexxa (pegloticase) / Horizon Therapeutics
GOUT DIAGNOSIS AND MANAGEMENT: AN AUDIT OF CURRENT OUTPATIENT PRACTICE () - May 21, 2021 - Abstract #ARA2021ARA_157;
Gout was well-managed in this tertiary care setting, with patients treated to target achieving positive clinical endpoints. In line with findings at other centres, achieving a target serum urate and disease remission were hampered primarily by patient adherence, rather than difficulty in accessing advanced therapies.
- |||||||||| Krystexxa (pegloticase) / Amgen
Trial completion: Study of Pegloticase (KRYSTEXXA (clinicaltrials.gov) - May 19, 2021
P4, N=14, Completed,
In line with findings at other centres, achieving a target serum urate and disease remission were hampered primarily by patient adherence, rather than difficulty in accessing advanced therapies. Active, not recruiting --> Completed
- |||||||||| Krystexxa (pegloticase) / Horizon Therapeutics
[VIRTUAL] Gout Management with Pegloticase in US Clinical Care; Observations from Trio Health and The American Rheumatology Network () - Apr 12, 2021 - Abstract #ISPOR2021ISPOR_938;
None of the 12 patients who discontinued due to infusion or allergic reactions received concurrent immune-modulating therapies. CONCLUSIONS : These observations suggest that treatment with pegloticase may be lengthened with concomitant use of immune-modulating therapies; however, a larger scale prospective study should be done to confirm to further elucidate the benefits of immunomodulation beyond durability of treatment, including safety benefits such as minimal to no infusion reactions.
- |||||||||| sirolimus / Generic mfg.
[VIRTUAL] IMMTOR NANOPARTICLES ENHANCE THE TOLEROGENIC ENVIRONMENT OF THE LIVER IN MICE (Room 4) - Apr 6, 2021 - Abstract #EULAR2021EULAR_1141;
Background: Tolerogenic ImmTOR biodegradable nanoparticles encapsulating rapamycin have been shown to mitigate the formation of anti-drug antibodies against pegadricase, a pegylated uricase enzyme, which enabled monthly dosing and sustained reduction of serum uric acid levels in a Phase 2 clinical trial of SEL-212, a combination of pegadricase + ImmTOR, in patients with symptomatic gout with hyperuricemia. These results suggest that the liver may contribute to the tolerogenic properties of ImmTOR in mitigating anti-drug antibody responses to biologic therapies, such as pegadricase.
- |||||||||| sirolimus / Generic mfg.
Review, Journal: Development of ImmTOR Tolerogenic Nanoparticles for the Mitigation of Anti-drug Antibodies. (Pubmed Central) - Mar 30, 2021
Human proof-of concept for the mitigation of ADAs has been demonstrated with SEL-212, a combination product consisting of ImmTOR + pegadricase, a highly immunogenic enzyme therapy for the treatment of gout. ImmTOR represents a promising approach to preventing the formation of ADAs to a broad range of biologic drugs.
- |||||||||| Krystexxa (pegloticase) / Horizon Therapeutics
[VIRTUAL] 378. Poster Presenters and Attendee Discussion () - Mar 2, 2021 - Abstract #NKFSCM2021NKF-SCM_793;
You will be able to move between breakout rooms and connect with multiple authors during this time. Below are our featured abstracts and authors: Pegloticase Therapy in Gout Patients Undergoing Dialysis: a USRDS Database Study Author: Brad Marder Zinc Deficient Intake in Hemodialysis Patients: A Path to a High Mortality Risk Author: Cristina Garagarza Engagement and Experiences in a Kidney Disease Patient-Centered Outcomes Research Study during Covid-19 Author: Shamika Jones Patient and Decision Partner Shared Decision-Making in Dialysis Author: Renata Sledge Organizational Predictors of High Quality Performance in Medicare’s Comprehensive End-Stage Renal Disease Care Initiative Author: Kelsey Drewry
- |||||||||| Krystexxa (pegloticase) / Horizon Therapeutics
[VIRTUAL] Pegloticase therapy in gout patients undergoing dialysis: a USRDS database study () - Mar 2, 2021 - Abstract #NKFSCM2021NKF-SCM_687;
CONCLUSION These data suggest that pegloticase is successfully being used in dialysis patients with uncontrolled gout with potentially lower ESA dose requirements after treatment. Clinical trials are needed to better understand pegloticase safety and efficacy in dialysis patients.
- |||||||||| Krystexxa (pegloticase) / Horizon Therapeutics
Clinical, Journal: Pegloticase hypersensitivity desensitisation: an outpatient, 3-bag, 12-step protocol. (Pubmed Central) - Feb 10, 2021
This is the first reported case of a patient successfully desensitised after an infusion reaction to pegloticase. Though additional patients are needed to confirm these results, this represents a significant opportunity to recapture and continue pegloticase therapy in patients treated for refractory gouty arthropathy.
- |||||||||| Zurampic (lesinurad) / AstraZeneca, Krystexxa (pegloticase) / Horizon Therapeutics, Uriadec (topiroxostat) / Fuji Yakuhin, Medca Japan
Retrospective data, Review, Journal: Evaluation of urate-lowering therapy in hyperuricemia patients: a systematic review and Bayesian network meta-analysis of randomized controlled trials. (Pubmed Central) - Feb 2, 2021
The new findings were as follows: (i) dual-agent ULTs were superior to febuxostat alone, and further surveillance on the adverse effects when lesinurad is uptitrated is needed, and (ii) terminalia bellerica 500 mg/day, a novel xanthine oxidase inhibitor (XOI) made of natural fruit extracts, and topiroxostat ≥ 80 mg/day, an XOI used mostly in Japan, could be new effective options for lowering the occurrence of adherence attrition events. Evidence from RCTs regarding second-line agents, such as probenecid and pegloticase, remains insufficient for clinical decision-making.Key Points• Dual-agent ULTs were superior to febuxostat alone, and further surveillance on the adverse-effects when lesinurad is uptitrated is needed.• Terminalia bellerica 500 mg/day, a novel xanthine oxidase inhibitor (XOI) made of natural fruit extracts, and topiroxostat 80 mg/day, an XOI used mostly in Japan, could be new effective options for lowering the occurrence of adherence attrition events.
- |||||||||| Krystexxa (pegloticase) / Amgen
Enrollment closed, Trial completion date, Trial primary completion date: PROTECT: Study of Pegloticase in Participants With Uncontrolled Gout Who Have Had a Kidney Transplant (clinicaltrials.gov) - Jan 31, 2021
P4, N=20, Active, not recruiting,
Future studies should include patients with CKD and should report study outcomes stratified by renal function. Recruiting --> Active, not recruiting | Trial completion date: Mar 2021 --> Sep 2021 | Trial primary completion date: Mar 2021 --> Jun 2021
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