Canakinumab for acute gouty arthritis in patients with limited treatment options: results from two randomised, multicentre, active-controlled, double-blind trials and their initial extensions

2012 ◽  
Vol 71 (11) ◽  
pp. 1839-1848 ◽  
Author(s):  
Naomi Schlesinger ◽  
Rieke E Alten ◽  
Thomas Bardin ◽  
H Ralph Schumacher ◽  
Mark Bloch ◽  
...  

ObjectivesGouty arthritis patients for whom non-steroidal anti-inflammatory drugs and colchicine are inappropriate have limited treatment options. Canakinumab, an anti-interleukin-1β monoclonal antibody, may be an option for such patients. The authors assessed the efficacy/safety of one dose of canakinumab 150 mg (n=230) or triamcinolone acetonide (TA) 40 mg (n=226) at baseline and upon a new flare in frequently flaring patients contraindicated for, intolerant of, or unresponsive to non-steroidal anti-inflammatory drugs and/or colchicine. Core study co-primary endpoints were pain intensity 72 h postdose (0–100 mm visual analogue scale and time to first new flare.MethodsTwo 12-week randomised, multicentre, active-controlled, double-blind, parallel-group core studies with double-blind 12-week extensions (response in acute flare and in prevention of episodes of re-flare in gout (β-RELIEVED and β-RELIEVED-II)).Results82.6% patients had comorbidities. Mean 72-h visual analogue scale pain score was lower with canakinumab (25.0 mm vs 35.7 mm; difference, −10.7 mm; 95% CI −15.4 to −6.0; p<0.0001), with significantly less physician-assessed tenderness and swelling (ORs=2.16 and 2.74; both p≤0.01) versus TA. Canakinumab significantly delayed time to first new flare, reduced the risk of new flares by 62% versus TA (HR: 0.38; 95% CI 0.26 to 0.57) in the core studies and by 56% (HR: 0.44; 95% CI 0.32 to 0.60; both p≤0.0001) over the entire 24-week period, and decreased median C-reactive protein levels (p≤0.0001 at 72 h and 7 days). Over the 24-week period, adverse events were reported in 66.2% (canakinumab) and 52.8% (TA) and serious adverse events were reported in 8.0% (canakinumab) and 3.5% (TA) of patients. Adverse events reported more frequently with canakinumab included infections, low neutrophil count and low platelet count.ConclusionCanakinumab provided significant pain and inflammation relief and reduced the risk of new flares in these patients with acute gouty arthritis.

2016 ◽  
Vol 97 (2) ◽  
pp. 217-221
Author(s):  
V N Shilenok ◽  
E V Nikitina

Aim. To conduct a comparative analysis of used anesthesia methods in patients with acute pancreatitis in intensive care units settings using pain scales.Methods. Depending on the anesthesia type, 44 patients with acute pancreatitis were divided into three groups: the first group received intramuscular injections of nonsteroidal anti-inflammatory drugs and spasmolytics, the second group - intramuscular injections of non-steroidal anti-inflammatory drugs and opioid analgesics, the third group - epidural anesthesia with local anesthetics. Comparative analysis of pain character, intensity was conducted, its dynamics in patients of all groups amid anesthesia was evaluated using a visual analogue scale, verbal rating scale, verbal descriptor scale, McGill pain questionnaire.Results. Baseline pain intensity in patients of all groups was high. Patients estimated this pain as «very strong». The time and the level of pain intensity reduction for various anesthesia types had differences. Pain syndrome was eliminated slower in patients of the second group. By the end of the 1st day, patients of this group continued to complain of «strong» pain. Pain intensity decreased only on the 2nd day - patients reported «moderate» pain. Pain syndrome was not completely eliminated in these patients for 2 days of anesthesia. 97.7% of patients reported that the visual analogue scale is the most acceptable pain assessment scale for them.Conclusion. In patients with acute pancreatitis, the most optimal anesthesia types are intramuscular nonsteroidal anti-inflammatory drugs with spasmolytics and prolonged epidural anesthesia with local anesthetics; intramuscular administration of opioid analgesics with non-steroidal anti-inflammatory drugs is less effective in relieving pain.


2013 ◽  
Vol 127 (11) ◽  
pp. 1106-1110 ◽  
Author(s):  
M H Baradaranfar ◽  
V Zand ◽  
M H Dadgarnia ◽  
S Atighechi

AbstractObjective:Tonsillectomy is a common operation performed in children and young adults. Pain and post-operation haemorrhage are its most common complications. This study was designed to evaluate the efficacy of topical antibiotics in reducing throat pain after tonsillectomy in adult patients.Methods:A double-blind, placebo-controlled, randomised clinical trial was conducted, enrolling 30 patients older than 18 years who were scheduled to undergo tonsillectomy. Patients were randomly assigned to receive either clindamycin or normal saline (as placebo). Throat pain severity was evaluated using a visual analogue scale.Results:All patients in both groups had experienced a reduction in pain by the seventh day after surgery. There was no statistically significant difference in the extent of visual analogue scale pain score reduction, comparing the placebo and clindamycin groups throughout the study course (p = 0.424).Conclusion:Topical clindamycin was not demonstrated to be more effective than normal saline in the reduction of throat pain following tonsillectomy in adults.


2020 ◽  
Vol 11 (4) ◽  
pp. 7160-7165
Author(s):  
Chitra Khanwelkar ◽  
Kartik Peethambaran ◽  
Sujata Jadhav

Oral proteolytic enzymes like serratiopeptidase are very commonly used by clinicians either alone or in combination with non-steroidal anti-inflammatory drugs for analgesia and anti-inflammatory purpose. As the activity of these drugs is not proved in trials, and they are not listed in any country's official pharmacopoeia, it was planned to study their effect in osteoarthritis patients. Two groups (n= 30 each) of diagnosed knee osteoarthritis patients, were treated with diclofenac 50 mg twice a day (BID) and serratiopeptidase 10mg three times a day (TID) + Diclofenac 50 mg BID for two weeks. The pain and difficulty in daily activities were assessed by Visual Analogue Scale (VAS) and Western Ontario and Mc Masters Universities Osteoarthritis (WOMAC OA) index scale before and after the treatment.  Highly significant improvement in both scales was seen in both groups. There was no statistically significant difference in the improvements found in both groups.  Addition of serratiopeptidase has not potentiated analgesic and anti-inflammatory effects of diclofenac. Thus, the analgesic and anti-inflammatory efficacy of serratiopeptidase are not proved.


2012 ◽  
Vol 39 (9) ◽  
pp. 1859-1866 ◽  
Author(s):  
H. RALPH SCHUMACHER ◽  
MANUELA F. BERGER ◽  
JULIE LI-YU ◽  
FERNANDO PEREZ-RUIZ ◽  
RUBÉN BURGOS-VARGAS ◽  
...  

Objective.To evaluate the analgesic efficacy of high-dose celecoxib in the treatment of moderate to extreme pain and inflammation associated with acute gouty arthritis.Methods.A multinational, randomized, double-blind, double-dummy, active-controlled trial was done with patients (aged ≥ 18 years) with acute gouty monoarthritis or oligoarthritis (onset of pain ≤ 48 h before enrollment). Patients were treated for 8 days with 1 week followup and were randomized 1:1:1:1 to receive celecoxib 50 mg bid, celecoxib 400 mg (followed by 200 mg later on Day 1 and then 200 mg bid for 7 days), celecoxib 800 mg (followed by 400 mg later on Day 1 and then 400 mg bid for 7 days), or indomethacin 50 mg tid.Results.Of 443 patients screened, 402 were randomized and 400 received treatment. Baseline demographics were comparable among treatments. Patients receiving high-dose celecoxib (800/400 mg) experienced a significantly greater reduction in pain intensity on Day 2 compared with low-dose celecoxib 50 mg bid [least squares (LS) mean difference −0.46; p = 0.0014]. For high-dose celecoxib 800/400 mg, the change in pain scores from baseline to Day 2 was comparable with indomethacin 50 mg tid (LS mean difference 0.11; p = 0.4331). There were significant differences in adverse events when the combined celecoxib groups (29.5%) were compared with patients taking indomethacin (43.1%; p = 0.0116). There was no change in median serum creatinine levels for any treatment. There were more discontinuations due to adverse events (8.8% vs 3%; p = 0.0147) with indomethacin than with the combined celecoxib groups.Conclusion.High-dose celecoxib (800/400 mg) was significantly more effective than low-dose celecoxib (50 mg bid) and comparable to indomethacin in the treatment of moderate to extreme pain in patients with acute gouty arthritis. Further, celecoxib was well tolerated.


2019 ◽  
Vol 56 ◽  
pp. 41-48 ◽  
Author(s):  
M. S. Eliseev ◽  
E. L. Nasonov

A significant part of patients with gout has contraindications to taking nonsteroidal anti-inflammatory drugs, colchicine and glucocorticoids. Such therapy is often ineffective, particularly in patients with the severe tophaceous gout what hampers treatment of acute arthritis attack assuming the need for other methods of therapy. During the last years several medications have been introduced the mechanism of anti-inflammatory action of which is associated with inhibition of interleukin 1 (IL1) playing a key role in the development of acute gouty arthritis. To date, the most well-studied and the only registered drug for relief of acute arthritis attack is canakinumab, recommended for use in situations where other therapy options are unacceptable. Despite these limitations, the use of IL1 inhibitors, in particular canakinumab, seems promising due to the high efficiency of the drug, the ability to use it in patients with comorbid diseases, as well as a favorable effect on the risk of cardiovascular disease.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Qiangqiang Zhao ◽  
Duanfeng Jiang ◽  
Xiaoying Sun ◽  
Qiuyu Mo ◽  
Shaobin Chen ◽  
...  

Abstract Background Non-Hodgkin’s lymphoma (NHL) is a malignant disease of lymphoid tissue. At present, chemotherapy is still the main method for the treatment of NHL. R-CHOP can significantly improve the survival rate of patients. Unfortunately, DOX is the main cytotoxic drug in R-CHOP and it can lead to adverse reactions. Therefore, it is particularly important to uncover new treatment options for NHL. Results In this study, a novel anti-tumor nanoparticle complex Nm@MSNs-DOX/SM was designed and constructed in this study. Mesoporous silica nanoparticles (MSNs) loaded with Doxorubicin (DOX) and anti-inflammatory drugs Shanzhiside methylester (SM) were used as the core of nanoparticles. Neutrophil membrane (Nm) can be coated with multiple nanonuclei as a shell. DOX combined with SM can enhance the anti-tumor effect, and induce apoptosis of lymphoma cells and inhibit the expression of inflammatory factors related to tumorigenesis depending on the regulation of Bcl-2 family-mediated mitochondrial pathways, such as TNF-α and IL-1β. Consequently, the tumor microenvironment (TME) was reshaped, and the anti-tumor effect of DOX was amplified. Besides, Nm has good biocompatibility and can enhance the EPR effect of Nm@MSNs-DOX/SM and increase the effect of active targeting tumors. Conclusions This suggests that the Nm-modified drug delivery system Nm@MSNs-DOX/SM is a promising targeted chemotherapy and anti-inflammatory therapy nanocomplex, and may be employed as a specific and efficient anti-Lymphoma therapy.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Vana Vukić ◽  
Ana Smajo ◽  
Mandica Vidović ◽  
Rudolf Vukojević ◽  
Miroslav Harjaček ◽  
...  

Abstract Background The last two decades brought new treatment options and high quality guidelines into the paediatric rheumatologic practice. Nevertheless, a number of patients still present a diagnostic and therapeutic challenge due to combination of vague symptoms and unresponsiveness to available treatment modalities. Case presentation We report a case of sixteen years old girl suffering from polyarticular type of juvenile idiopathic arthritis refractory to multiple treatment options. She first presented at the age of 4 with swelling and contractures of both knees. Her symptoms were initially unresponsive to nonsteroidal anti-inflammatory drugs and progressed despite treatment with intraarticular and systemic glucocorticoids and methotrexate. Throughout the years, she received several biologics together with continuous administration of nonsteroidal anti-inflammatory drugs and disease modifying anti-rheumatic drugs as well as intraarticular and systemic glucocorticoids in disease flares. However, none of this options  provided a permanent remission, so various other modalities, as well as other possible diagnoses were constantly being considered. Eventually she became dependent on a daily dose of systemic glucocorticoids. In 2018, the treatment with Janus kinase inhibitor tofacitinib was initiated, which led to gradual amelioration of musculoskeletal symptoms, improvement of inflammatory markers and overall well-being, as well as to the weaning of systemic glucocorticoids. As the swelling of the wrists subsided for the first time in many years, Madelung’s deformity was noticed, first clinically, and later radiographically as well. Genetic analysis revealed short-stature homeobox gene deficiency and confirmed the diagnosis of Leri Weill syndrome. Conclusions This case report emphasizes the need for reporting refractory, complicated cases from everyday clinical practice in order to build-up the overall knowledge and share experience which is complementary to available guidelines. Individual reports of difficult to treat cases, especially when additional diagnoses are involved, can be helpful for physicians treating patients with common rheumatological diseases such as juvenile idiopathic arthritis.


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