scholarly journals Reasons for canakinumab initiation among patients with periodic fever syndromes: a retrospective medical chart review from the United States

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Peter Hur ◽  
Kathleen G. Lomax ◽  
Raluca Ionescu-Ittu ◽  
Ameur M. Manceur ◽  
Jipan Xie ◽  
...  
Keyword(s):  
Safety Profile ◽  
Periodic Fever ◽  
Previous Treatment ◽  
The United States ◽  
Periodic Syndrome ◽  
Perceived Efficacy ◽  
Periodic Fever Syndromes ◽  
Favorable Safety Profile ◽  
Fever Syndromes ◽  
Favorable Safety

Abstract Background Although canakinumab has demonstrated efficacy in multiple trials in patients with periodic fever syndromes (PFS), the evidence on initiation of canakinumab among PFS patients in real world setting is not well understood. We aimed to characterize the reasons for canakinumab initiation among patients with PFS, specifically, cryopyrin-associated periodic syndrome (CAPS), hyperimmunoglobulin D syndrome/mevalonate kinase deficiency (HIDS/MKD), TNF receptor-associated periodic syndrome (TRAPS) and familial Mediterranean fever (FMF). Methods Physicians retrospectively reviewed the medical charts of PFS patients prescribed canakinumab between 2016 and 2018. Information collected included patient clinical characteristics, reasons for previous treatment discontinuation and canakinumab initiation. The results were summarized for overall patients, and by children (< 18 years) and adults and by subtype of PFS. Results Fifty-eight physicians in the US (rheumatologists, 44.8 %; allergists/immunologists, 29.3 %; dermatologists, 25.9 %) abstracted information for 147 patients (children, 46.3 %; males, 57.1 %; CAPS, 36.7 %; TRAPS, 26.5 %; FMF, 26.5 %; HIDS/MKD, 6.8 %; Mixed, 3.4 %). Overall, most patients (90.5 %) received treatment directly preceding canakinumab (NSAIDs, 27.8 % [40.0 % in HIDS/MKD]; anakinra, 24.1 % [32.7 % in CAPS]; colchicine, 21.8 % [35.9 % in FMF]), which were discontinued due to lack of efficacy/effectiveness (39.5 %) and availability of a new treatment (36.1 %). The common reasons for canakinumab initiation were physician perceived efficacy/effectiveness (81.0 %; children, 75.0 %; adults, 86.1 %), lack of response to previous treatment (40.8 %; children, 38.2 %; adults, 43.0 %) and favorable safety profile/tolerability (40.1 %; children, 42.6 %; adults, 38.0 %). Within subtypes, efficacy/effectiveness was the most stated reason for canakinumab initiation in HIDS/MKD (90.9 %), lack of response to previous treatment in FMF (52.4 %) and convenience of administration/dosing in CAPS (27.1 %). Conclusions This study provided insights into how canakinumab is initiated in US clinical practice among PFS patients, with physician perceived efficacy/effectiveness of canakinumab, lack of response to previous treatment and favorable safety profile/tolerability of canakinumab being the dominant reasons for canakinumab initiation in all patients and in children and adults and PFS subtypes. Notably, the favorable safety profile/tolerability of canakinumab was more often the reason for initiation among children versus adults.

scholarly journals MO961KIDNEY TRANSPLANTATION AS A TREATMENT OF CHOICE FOR AA AMYLOIDOSIS DUE TO PERIODIC FEVER SYNDROME

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Ivana Dedinska ◽  
Karol Graňák ◽  
Matej Vnučák
Keyword(s):  
Early Childhood ◽  
Kidney Transplantation ◽  
Clinical Course ◽  
Periodic Fever ◽  
Periodic Fever Syndrome ◽  
Aa Amyloidosis ◽  
Periodic Fever Syndromes ◽  
Post Transplant ◽  
Fever Syndromes ◽  
End Stage

Abstract Background and Aims Renal AA amyloidosis is the most serious complication of periodic fever syndrome, which, inadequate suppression, due to persistent inflammation, leads to nephrotic syndrome and renal failure over several years. In most cases, periodic fever syndromes begin to manifest clinically in early childhood. Occurrence in adulthood is considered rare and is associated with a poorer clinical course. Kidney transplantation is an effective and safe treatment for end-stage chronic kidney disease (CKD) based on AA amyloidosis. Method We present cases of two patients after deceased donor kidney transplantation, who have been diagnosed with adult periodic fever syndrome. Conclusion Periodic fever syndromes are diseases beginning to manifest clinically in early childhood in 60–90% of cases, most often in the case of familial Mediterranean fever around 4 years of age, in the case of CAPS usually only a few months after birth. Occurrence in adulthood is considered rare and is associated with a poorer clinical course. Kidney transplantation is an effective and safe treatment of end-stage CKD based on AA amyloidosis associated with periodic fever syndrome. Adequate targeted treatment against IL-1 or TNF is important and appears to be safe during the post-transplant period, with regular monitoring of renal function, acute phase inflammatory reactants, and histological findings by protocol graft biopsies. It will be important and necessary to assess the development of diseases in the post-transplant period in the long term.

Safety of darolutamide (DARO) for nonmetastatic castration-resistant prostate cancer (nmCRPC) from extended follow-up in the phase III ARAMIS trial.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 239-239
Author(s):  
Matthew Raymond Smith ◽  
Karim Fizazi ◽  
Teuvo L. J. Tammela ◽  
Felipe Melo Cruz ◽  
Luke T. Nordquist ◽  
...  
Keyword(s):  
Safety Profile ◽  
Safety Data ◽  
Final Analysis ◽  
Phase Iii ◽  
Prolonged Treatment ◽  
Fracture Rate ◽  
Castration Resistant Prostate Cancer ◽  
Favorable Safety Profile ◽  
Risk Of Death ◽  
Favorable Safety

239 Background: DARO is a structurally distinct androgen receptor inhibitor (ARI) approved for treating nmCRPC. In ARAMIS, DARO significantly reduced the risk of death by 31% (HR = 0.69; 95% CI: 0.53-0.88; p = 0.003) and prolonged median metastasis-free survival vs placebo (PBO; 40.4 months vs 18.4 months; HR = 0.41; 95% CI: 0.34-0.50; p < 0.001). Adverse events (AEs) of interest commonly associated with ARI therapy, such as fatigue, falls, fractures, rash, mental impairment, and hypertension, as well as interactions between ARIs and concomitantly administered drugs, can impact patient daily life. In the final analysis of the double-blind (DB) period of the ARAMIS trial, DARO had a favorable safety profile, showing ≤2% difference vs PBO for most AEs of interest. Fatigue was the only AE with > 10% incidence with DARO. The incidence of permanent discontinuation due to AEs was also similar between DARO and PBO (8.9% vs 8.7%). Here we present safety data for prolonged treatment with DARO from the final analysis of the DB + open-label (OL) period of ARAMIS. Methods: Patients (pts) with nmCRPC (N = 1509) were randomized 2:1 to DARO or matched PBO while continuing androgen deprivation therapy. The data cut-off for the primary analysis of the DB period was September 3, 2018. Study unblinding occurred on November 30, 2018, after which pts in the DARO arm still receiving study treatment continued with OL DARO. The data cut-off for final analysis of the DB+OL period was November 15, 2019. Results: At the final analysis, the median treatment duration for pts randomized to DARO was 18.5 months for the DB period and 25.8 months for the DB+OL period. At the final cut-off date, 48.8% of patients in the DARO DB+OL group were still receiving DARO treatment. The increase in the incidence of any-grade AEs (85.7% vs 89.8%) and serious AEs (26.1% vs 32.1%) between the DB and DB+OL period was small. Between the DB and DB+OL periods, only minor numerical changes for ARI-associated AEs were observed. When the incidences were corrected for exposure, there were minimal differences between the DB and DB+OL period, e.g., the fracture rate was 3.4 vs 4.0 per 100 patient-years for the DB vs DB+OL periods, respectively. Fatigue was the only ARI-associated AE of interest that exhibited > 10% incidence in the DARO arm during the DB+OL period. The incidence of permanent discontinuation of DARO due to AEs increased slightly from 8.9% during the DB period to 10.5% during the DB+OL period; the incidence of discontinuation of PBO due to AEs during the DB period was 8.7%. Conclusions: With longer treatment exposure, DARO remained well-tolerated. In the DB+OL period, no new safety signals were observed. The expected increases in incidence of AEs between the DB and DB+OL periods largely disappeared when adjusted for the longer exposure, confirming the favorable safety profile of DARO with prolonged treatment. Clinical trial information: NCT02200614.

Hereditary periodic fever syndromes

2020 ◽  
pp. 2207-2218
Author(s):  
Helen J. Lachmann ◽  
Stefan Berg ◽  
Philip N. Hawkins
Keyword(s):  
Clinical Features ◽  
Periodic Fever ◽  
Mevalonate Kinase ◽  
Tnf Receptor ◽  
Aa Amyloidosis ◽  
Periodic Fever Syndromes ◽  
Hereditary Periodic Fever Syndromes ◽  
Hereditary Periodic Fever ◽  
Fever Syndromes ◽  
Wells Syndrome

The hereditary periodic fever syndromes or hereditary autoinflammatory diseases are disorders of innate immunity that mostly present in childhood and are characterized by recurrent, self-limiting, seemingly unprovoked episodes of fever and systemic inflammation that occur in the absence of autoantibody production or identifiable infection. Disorders include (1) familial Mediterranean fever (FMF), due to mutations in the gene encoding pyrin; (2) tumour necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS), due to mutations in a gene for a TNF receptor; (3) mevalonate kinase deficiency and period fever (MKD), caused by mutations in the mevalonate kinase gene; and (4) the cryopyrin-associated periodic syndromes (CAPS), which include (a) familial cold urticarial syndrome, (b) Muckle–Wells syndrome, and (c) chronic infantile neurological, cutaneous, and articular syndrome. With advances in genetics, further syndromes are continually being recognized. These are all extremely rare and in the majority are only known to affect a handful of kindred or individuals. Diagnosis relies on recognition of suggestive clinical features that are almost always accompanied by a substantial acute phase response, and is supported by genetic testing. With the exception of FMF, which is a common disease in certain geographic areas, hereditary periodic fever syndromes are rare and easily overlooked in the differential diagnosis of recurrent fevers. Clinical features and management—attacks can be mild to debilitating and short to prolonged, while their most feared complication is AA amyloidosis. Effective therapies are available for some syndromes, for example: (1) FMF—daily prophylactic colchicine prevents clinical attacks and susceptibility to AA amyloidosis, (2) CAPS—treatment with anti-IL-1 agents produces rapid and often complete clinical and serological remission, and (3) TRAPS—anti-IL therapies are extremely effective.

scholarly journals IL-1 Inhibitors in the Treatment of Monogenic Periodic Fever Syndromes: From the Past to the Future Perspectives

2021 ◽  
Vol 11 ◽  
Author(s):  
Hana Malcova ◽  
Zuzana Strizova ◽  
Tomas Milota ◽  
Ilja Striz ◽  
Anna Sediva ◽  
...  
Keyword(s):  
Periodic Fever ◽  
Tumor Necrosis Factor Receptor ◽  
Systemic Juvenile Idiopathic Arthritis ◽  
Clinical Manifestations ◽  
Musculoskeletal Symptoms ◽  
Mevalonate Kinase Deficiency ◽  
Periodic Fever Syndromes ◽  
Therapeutic Uses ◽  
Fever Syndromes ◽  
Mediterranean Fever

Autoinflammatory diseases (AIDs) represent a rare and heterogeneous group of disorders characterized by recurrent episodes of inflammation and a broad range of clinical manifestations. The most common symptoms involve recurrent fevers, musculoskeletal symptoms, and serositis; however, AIDs can also lead to life-threatening complications, such as macrophage activation syndrome (MAS) and systemic AA amyloidosis. Typical monogenic periodic fever syndromes include cryopyrin-associated periodic fever syndrome (CAPS), tumor necrosis factor receptor-associated periodic syndrome (TRAPS), mevalonate kinase deficiency/hyper IgD syndrome (MKD/HIDS), and familial Mediterranean fever (FMF). However, a number of other clinical entities, such as systemic juvenile idiopathic arthritis (sJIA), adult-onset Still’s disease (AOSD), Kawasaki disease (KD) and idiopathic recurrent pericarditis (IRP), display similar phenotypical and immunological features to AIDs. All these diseases are pathophysiologicaly characterized by dysregulation of the innate immune system and the central pathogenic role is attributed to the IL-1 cytokine family (IL-1α, IL-1β, IL-1Ra, IL-18, IL-36Ra, IL-36α, IL-37, IL-36β, IL-36g, IL-38, and IL-33). Therefore, reasonable therapeutic approaches aim to inhibit these cytokines and their pathways. To date, several anti-IL-1 therapies have evolved. Each drug differs in structure, mechanism of action, efficacy for the treatment of selected diseases, and side effects. Most of the available data regarding the efficacy and safety of IL-1 inhibitors are related to anakinra, canakinumab, and rilonacept. Other promising therapeutics, such as gevokizumab, tadekinig alfa, and tranilast are currently undergoing clinical trials. In this review, we provide sophisticated and up-to-date insight into the therapeutic uses of different IL-1 inhibitors in monogenic periodic fever syndromes.

scholarly journals Brief Report: AA Amyloidosis Complicating the Hereditary Periodic Fever Syndromes

2013 ◽  
Vol 65 (4) ◽  
pp. 1116-1121 ◽  
Author(s):  
Thirusha Lane ◽  
Jutta M. Loeffler ◽  
Dorota M. Rowczenio ◽  
Janet A. Gilbertson ◽  
Alison Bybee ◽  
...  
Keyword(s):  
Periodic Fever ◽  
Aa Amyloidosis ◽  
Periodic Fever Syndromes ◽  
Hereditary Periodic Fever Syndromes ◽  
Hereditary Periodic Fever ◽  
Fever Syndromes
Sign in / Sign up

Export Citation Format

Share Document