Long-term surveillance of biologic therapies in systemic-onset juvenile idiopathic arthritis: data from the German BIKER registry

Rheumatology ◽  
2019 ◽  
Vol 59 (9) ◽  
pp. 2287-2298 ◽  
Author(s):  
Ariane Klein ◽  
Jens Klotsche ◽  
Boris Hügle ◽  
Kirsten Minden ◽  
Anton Hospach ◽  
...  
Keyword(s):  
Adverse Event ◽  
Adverse Events ◽  
Special Interest ◽  
Poisson Model ◽  
Incidence Rates ◽  
Serious Adverse Events ◽  
Mixed Effect ◽  
Long Term Treatment ◽  
Systemic Onset

Abstract Objective Using data from the German Biologics JIA Registry (BIKER), long-term safety of biologics for systemic-onset JIA with regard to adverse events of special interest was assessed. Methods Safety assessments were based on adverse event reports after first dose through 90 days after last dose. Rates of adverse event, serious adverse event and 25 predefined adverse events of special interest were analysed. Incidence rates were compared for each biologic against all other biologics combined applying a mixed-effect Poisson model. Results Of 260 systemic-onset JIA patients in this analysis, 151 patients received etanercept, 109 tocilizumab, 71 anakinra and 51 canakinumab. Patients with etanercept had higher clinical Juvenile Arthritis Disease Activity Score 10 scores, active joint counts and steroid use at therapy start. Serious adverse events were reported with higher frequency in patients receiving canakinumab [20/100 patient years (PY)] and tocilizumab (21/100 PY). Cytopenia and hepatic events occurred with a higher frequency with tocilizumab and canakinumab. Medically important infections were seen more often in patients with IL-6 or IL-1 inhibition. Macrophage activation syndrome occurred in all cohorts with a higher frequency in patients with canakinumab (3.2/100 PY) and tocilizumab (2.5/100 PY) vs anakinra (0.83/100 PY) and etanercept (0.5/100 PY). After adjustment only an elevated risk for infections in anakinra-treated patients remained significant. Three definite malignancies were reported in patients ever exposed to biologics. Two deaths occurred in patients treated with etanercept. Conclusion Surveillance of pharmacotherapy as provided by BIKER is an import approach especially for patients on long-term treatment. Overall, tolerance was acceptable. Differences between several biologics were noted and should be considered in daily patient care.

scholarly journals Long-term safety and effectiveness of canakinumab therapy in patients with cryopyrin-associated periodic syndrome: results from the β-Confident Registry

RMD Open ◽  
2021 ◽  
Vol 7 (2) ◽  
pp. e001663
Author(s):  
Ulrich A Walker ◽  
Hugh H Tilson ◽  
Philip N Hawkins ◽  
Tom van der Poll ◽  
Stephanie Noviello ◽  
...  
Keyword(s):  
Adverse Events ◽  
Disease Activity ◽  
Rectal Adenocarcinoma ◽  
Routine Care ◽  
Incidence Rates ◽  
Term Treatment ◽  
Serious Adverse Events ◽  
Long Term Treatment ◽  
Wells Syndrome

ObjectiveTo report the long-term safety and effectiveness of canakinumab, a fully human anti-interleukin 1β monoclonal antibody, in patients with cryopyrin-associated periodic syndromes (CAPS), including familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS) and neonatal-onset multisystem inflammatory disease (NOMID), in a real-world setting.MethodsFrom December 2009 to December 2015, the β-Confident Registry prospectively enrolled patients with CAPS and non-CAPS conditions who received canakinumab per routine care and were prospectively followed for up to 6 years. The registry protocol did not mandate specific visits or procedures; however, all observed adverse events (AEs) and serious adverse events (SAEs) had to be recorded. Canakinumab effectiveness was evaluated by Physician’s Global Assessment (PGA).ResultsOf 288 patients enrolled, 3 were excluded due to missing informed consent. Among the remaining 285 patients, 243 (85.3%) were patients with CAPS and 42 (14.7%) had atypical CAPS (6.3%) or other conditions (8.4%). The median age was 26.6 years. Based on PGA, 58 of 123 (47.2%) patients with CAPS had no disease activity at 48 months, and 65 of 123 (52.8%) experienced mild/moderate disease activity at 48 months. Among CAPS phenotypes, AE incidence rates per 100 patient-years were lowest for FCAS (73.1; 95% CI 60.3 to 87.8) compared with those with MWS (105.0; 95% CI 97.2 to 113.2) or NOMID (104.6; 95% CI 86.6 to 125.2). One hundred twenty-eight SAEs were reported in 68 patients with CAPS (incidence rate/100 patient-years, 14.0; 95% CI 11.6 to 16.6). One death (metastatic rectal adenocarcinoma in a patient with MWS) was reported.ConclusionsThe response to canakinumab was sustained for up to 6 years. Canakinumab demonstrated a favourable safety profile over long-term treatment in patients with CAPS.Trial registration numberNCT01213641.

scholarly journals Reducing the Toxicity of Long-Term Glucocorticoid Treatment in Large Vessel Vasculitis

2020 ◽  
Vol 22 (12) ◽  
Author(s):  
Andriko Palmowski ◽  
Frank Buttgereit
Keyword(s):  
Adverse Events ◽  
Takayasu Arteritis ◽  
Term Treatment ◽  
Large Vessel Vasculitis ◽  
Large Vessel ◽  
Serious Adverse Events ◽  
Glucocorticoid Treatment ◽  
Long Term Treatment ◽  
Higher Doses

Abstract Purpose While glucocorticoids (GCs) are effective in large vessel vasculitis (LVV), they may cause serious adverse events (AEs), especially if taken for longer durations and at higher doses. Unfortunately, patients suffering from LVV often need long-term treatment with GCs; therefore, toxicity needs to be expected and countered. Recent Findings GCs remain the mainstay of therapy for both giant cell arteritis and Takayasu arteritis. In order to minimize their toxicity, the following strategies should be considered: GC tapering, administration of conventional synthetic (e.g., methotrexate) or biologic (e.g., tocilizumab) GC-sparing agents, as well as monitoring, prophylaxis, and treatment of GC-related AEs. Several drugs are currently under investigation to expand the armamentarium for the treatment of LVV. Summary GC treatment in LVV is effective but associated with toxicity. Strategies to minimize this toxicity should be applied when treating patients suffering from LVV.

scholarly journals Pomaglumetad Methionil (LY2140023 Monohydrate) and Aripiprazole in Patients with Schizophrenia: A Phase 3, Multicenter, Double-Blind Comparison

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
David H. Adams ◽  
Lu Zhang ◽  
Brian A. Millen ◽  
Bruce J. Kinon ◽  
Juan-Carlos Gomez
Keyword(s):  
Weight Gain ◽  
Adverse Events ◽  
Term Treatment ◽  
Phase 3 ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Treatment Groups ◽  
Long Term Treatment ◽  
Blind Comparison

We tested the hypothesis that long-term treatment with pomaglumetad methionil would demonstrate significantly less weight gain than aripiprazole in patients with schizophrenia. In this 24-week, multicenter, randomized, double-blind, Phase 3 study, 678 schizophrenia patients were randomized to either pomaglumetad methionil (n=516) or aripiprazole (n=162). Treatment groups were also compared on efficacy and various safety measures, including serious adverse events (SAEs), discontinuation due to adverse events (AEs), treatment-emergent adverse events (TEAEs), extrapyramidal symptoms (EPS), and suicide-related thoughts and behaviors. The pomaglumetad methionil group showed significantly greater weight loss at Week 24 (Visit 12) compared with the aripiprazole group (−2.8 ± 0.4 versus 0.4 ± 0.6;P<0.001). However, change in Positive and Negative Syndrome Scale (PANSS) total scores for aripiprazole was significantly greater than for pomaglumetad methionil (−15.58 ± 1.58 versus −12.03 ± 0.99;P=0.045). The incidences of SAEs (8.2% versus 3.1%;P=0.032) and discontinuation due to AEs (16.2% versus 8.7%;P=0.020) were significantly higher for pomaglumetad methionil compared with aripiprazole. No statistically significant differences in the incidence of TEAEs, EPS, or suicidal ideation or behavior were noted between treatment groups. In conclusion, long-term treatment with pomaglumetad methionil resulted in significantly less weight gain than aripiprazole. This trial is registered with ClinicalTrials.govNCT01328093.

scholarly journals Spotlight on eltrombopag in pediatric ITP in China: a long-term observational study in real-world practice

2021 ◽  
Vol 5 (19) ◽  
pp. 3799-3806
Author(s):  
Xiaoling Cheng ◽  
LingLing Fu ◽  
Jingyao Ma ◽  
Hao Gu ◽  
Zhenping Chen ◽  
...  
Keyword(s):  
Adverse Events ◽  
Pediatric Patients ◽  
Complete Response ◽  
Term Treatment ◽  
Serious Adverse Events ◽  
Platelet Counts ◽  
Chronic Itp ◽  
Long Term Treatment ◽  
Concomitant Medications

Abstract Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder with isolated thrombocytopenia and risk of hemorrhage. Treatment with eltrombopag increases and maintains hemostatic platelet counts; however, to date, long-term data are lacking on the outcome of children with ITP who are treated with eltrombopag. This prospective, observational, longitudinal cohort study evaluated the efficacy and safety of eltrombopag in pediatric patients with persistent or chronic ITP. For the 116 pediatric patients enrolled, duration of eltrombopag treatment was at least 3 months. Median effective dose was 25 mg/day, 50 mg/day, and 50 mg/day, respectively, for children age 5 years or younger, 6 to 11 years, or 12 years or older. In all, 89 patients (76.7%) achieved overall response, 53 (45.7%) achieved complete response, and 36 (31.0%) achieved response. Median platelet counts increased by week 1 and were sustained throughout the treatment period. During treatment with eltrombopag, the proportion of patients with grade 1 to 4 bleeding symptoms decreased from 83.61% at baseline to 9.88% at 6 months when only grade 1 was reported. Forty-three patients (37.1%) reported using concomitant medications at study entry, which was reduced to 1 patient (2.5%) who needed concomitant medications at 12 months. All adverse events were grade 1 or 2 according to Common Terminology Criteria for Adverse Events. No serious adverse events, cataracts, malignancies, or thromboses were reported during the study. Long-term treatment with eltrombopag was generally safe, well tolerated, and effective in maintaining platelet counts and reducing bleeding in most pediatric patients with persistent or chronic ITP. Combined with future studies, these findings will help establish how eltrombopag should best be used in the management of pediatric patients with East Asian ancestry.

Long-term treatment of endometriosis with dienogest: Real-world results from the VIPOS study

2021 ◽  
pp. 228402652199368
Author(s):  
Sabine Moehner ◽  
Kerstin Becker ◽  
Jens A Lange ◽  
Sophia von Stockum ◽  
Marco Serrani ◽  
...  
Keyword(s):  
Adverse Events ◽  
Real World ◽  
Health Care Professionals ◽  
Study Entry ◽  
Safety Signal ◽  
Real World Data ◽  
Serious Adverse Events ◽  
Long Term Treatment

Introduction: The Visanne Post-approval Observational Study (VIPOS) was designed to assess the safety of dienogest 2 mg (DNG, Visanne) compared to other hormonal endometriosis treatments. Methods: Large, prospective, non-interventional, active surveillance study in six European countries (Germany, Poland, Russia, Hungary, Switzerland, and Ukraine). Women with a new hormonal therapy for endometriosis were enrolled by gynecologists and specialized centers between 2010 and 2016 and observed for up to 7 years. Self-administered questionnaires during study entry and follow-up collected information on baseline characteristics, health status and endometriosis treatment. Self-reported clinical outcomes of interest were validated by health care professionals. Results: Among the >27,000 enrolled participants, 3262 women started DNG use either at study entry or during follow-up. A total of 798 study participants used DNG during follow-up continuously for 15 months or longer (DNG long-term users). When comparing the occurrence of serious adverse events (SAE) in users treated with DNG, no safety signal emerged for long-term users; the SAE incidence rate per 10,000 women-years was 367.7 (95% CI: 274.1–481.9) in DNG long-term users and 416.4 (349.1–492.5) in short-term users (treated with DNG for less than 15 months). Conclusions: Previous data on DNG long-term safety were derived from studies with relatively low numbers of patients and limited follow-up time. VIPOS provided valuable real-world data on the long-term use of DNG 2 mg in around 800 women treated in Europe and observed no safety signal regarding serious adverse events.

scholarly journals Automated summaries of serious adverse events in the hepatitis C antiviral long-term treatment against cirrhosis trial

2009 ◽  
Vol 6 (6) ◽  
pp. 618-627 ◽  
Author(s):  
Margaret C Bell ◽  
Patricia R Robuck ◽  
Elizabeth C Wright ◽  
Marina S Mihova ◽  
Charlotte Hofmann ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Adverse Events ◽  
Term Treatment ◽  
Serious Adverse Events ◽  
Long Term Treatment

Tolerability and Efficacy of Naratriptan Tablets with Long-Term Treatment (6 Months)

Cephalalgia ◽  
1998 ◽  
Vol 18 (1) ◽  
pp. 33-37 ◽  
Author(s):  
MAM Bomhof ◽  
J Heywood ◽  
A Pradalier ◽  
H Enahoro ◽  
P Winter ◽  
...  
Keyword(s):  
Adverse Event ◽  
Adverse Events ◽  
Median Number ◽  
Term Treatment ◽  
Open Label ◽  
Long Term Treatment ◽  
Term Tolerability ◽  
Treat All ◽  
Headache Recurrence

This open-label study was conducted to examine the long-term tolerability and efficacy of the novel 5HT1 agonist naratriptan tablets 2.5 mg used to treat all migraine attacks for 6 months. Patients could reduce the dose to 1 mg in the event of intolerable adverse events. The results demonstrate that the majority (median 83%) of attacks treated with naratriptan tablets 2.5 mg were not associated with an adverse event. Among attacks treated with naratriptan tablets 2.5 mg (+optional 2.5 mg for headache recurrence), the most frequently reported adverse event was nausea (4% of attacks after a single naratriptan dose). Both the overall incidence of adverse events and the incidences of specific adverse events were no higher during months 4-6 of treatment compared with months 1-3. Only 5 of 414 patients elected to reduce their naratriptan dose to 1 mg. Headache relief 4 h postdose was reported in a mean of 68% of 6770 moderate or severe migraine attacks treated with naratriptan tablets 2.5 mg. The median number of naratriptan tablets used per attack was 1.0 (mean 1.25); patients treated only a median 7% of attacks (mean 13%) with a 2nd naratriptan tablet for headache recurrence. Patients rated naratriptan tablets as good or excellent in 61% of 7566 treated attacks. In summary, the data from this study demonstrate that naratriptan tablets 2.5 mg were very well tolerated and effective for the acute treatment of migraine for 6 months in a situation closely resembling actual clinical use.

scholarly journals Adverse events of special interest in clinical trials of rheumatoid arthritis, psoriatic arthritis, ulcerative colitis and psoriasis with 37 066 patient-years of tofacitinib exposure

RMD Open ◽  
2021 ◽  
Vol 7 (2) ◽  
pp. e001595
Author(s):  
Gerd R Burmester ◽  
Peter Nash ◽  
Bruce E Sands ◽  
Kim Papp ◽  
Lori Stockert ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Ulcerative Colitis ◽  
Clinical Trials ◽  
Psoriatic Arthritis ◽  
Adverse Events ◽  
Special Interest ◽  
Phase 1 ◽  
Incidence Rates ◽  
Study Data ◽  
System Organ Class

ObjectivesTo analyse adverse events (AEs) of special interest across tofacitinib clinical programmes in rheumatoid arthritis (RA), psoriatic arthritis (PsA), ulcerative colitis (UC) and psoriasis (PsO), and to determine whether the incidence rates (IRs; unique patients with events per 100 patient-years) of these events are consistent across diseases.MethodsThe analysis included data from patients exposed to ≥1 dose of tofacitinib in phase 1, 2, 3 or 3b/4 clinical trials and long-term extension (LTE) studies (38 trials) in RA (23 trials), PsA (3 trials), UC (5 trials) and PsO (7 trials). All studies were completed by or before July 2019, except for one ongoing UC LTE study (data cut-off May 2019). IRs were obtained for AEs of special interest.Results13 567 patients were included in the analysis (RA: n=7964; PsA: n=783; UC: n=1157; PsO: n=3663), representing 37 066 patient-years of exposure. Maximum duration of exposure was 10.5 years (RA). AEs within the ‘infections and infestations’ System Organ Class were the most common in all diseases. Among AEs of special interest, IRs were highest for herpes zoster (non-serious and serious; 3.6, 1.8, 3.5 and 2.4 for RA, PsA, UC and PsO, respectively) and serious infections (2.5, 1.2, 1.7 and 1.3 for RA, PsA, UC and PsO, respectively). Age-adjusted and sex-adjusted mortality ratios (weighted for country) were ≤0.2 across cohorts.ConclusionsThe tofacitinib safety profile in this analysis was generally consistent across diseases and with longer term follow-up compared with previous analyses.

Parenteral Iron Therapy: A Single Institution's Experience Over a 5-Year Period

2005 ◽  
Vol 3 (6) ◽  
pp. 791-795 ◽  
Author(s):  
Christopher A. Laman ◽  
Scott B. Silverstein ◽  
George M. Rodgers
Keyword(s):  
Adverse Event ◽  
Adverse Events ◽  
Iron Sucrose ◽  
Iron Therapy ◽  
Iron Dextran ◽  
Serious Adverse Events ◽  
Exact Test ◽  
Parenteral Iron ◽  
Parenteral Iron Therapy ◽  
Event Rates

Many patients require parenteral iron therapy for optimal correction of anemia, including cancer patients who require erythropoietic drugs. Available parenteral iron therapy options include iron dextran, iron gluconate, and iron sucrose. The purpose of this study is to summarize our institution's experience with parenteral iron therapy over a 5-year period, with a focus on comparative safety profiles. All patients receiving parenteral iron therapy over this period were included in the analysis. Chi-squared test and Fisher's exact test were used to compare the adverse event rates of each product. A total of 121 patients received 444 infusions of parenteral iron over this period. Iron dextran was the most commonly used product (85 patients) and iron sucrose was the least used (2 patients). Iron gluconate was used by 34 patients. Overall adverse event rates per patient with iron dextran and iron gluconate were 16.5% and 5.8%, respectively (P = .024). Premedication with diphenhydramine and acetaminophen before infusions of iron dextran reduced adverse event rates per infusion from 12.3% to 4.4% (P = .054). Test doses of iron dextran were used 88% of the time for initial infusions of iron dextran. All adverse events for all parenteral iron products were mild or moderate. There were no serious adverse events and no anaphylaxis was observed. Our results suggest that, if test doses and premedications are used, iron dextran is an acceptable product to treat iron deficiency.

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