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The Review of Diabetic Studies : RDS 2014Glucagon-like peptide-1 (GLP-1) receptor agonists are a class of injective anti-diabetic drugs that improve glycemic control and many other atherosclerosis-related... (Review)
Review
Glucagon-like peptide-1 (GLP-1) receptor agonists are a class of injective anti-diabetic drugs that improve glycemic control and many other atherosclerosis-related parameters in patients with type 2 diabetes (T2D). However, the use of this relatively new class of drugs may be associated with certain adverse effects. Concerns have been expressed regarding the effects of these drugs on pancreatic and thyroid tissue, since animal studies and analyses of drug databases indicate an association of GLP-1 receptor agonists with pancreatitis, pancreatic cancer, and thyroid cancer. However, several meta-analyses failed to confirm a cause-effect relation between GLP-1 receptor agonists and the development of these adverse effects. One benefit of GLP-1 receptor agonists is that they do not cause hypoglycemia when combined with metformin or thiazolidinediones, but the dose of concomitant sulphonylurea or insulin may have to be decreased to reduce the risk of hypoglycemic episodes. On the other hand, several case reports have linked the use of these drugs, mainly exenatide, with the occurrence of acute kidney injury, primarily through hemodynamic derangement due to nausea, vomiting, and diarrhea. The most common symptoms associated with the use of GLP-1 receptor agonists are gastrointestinal symptoms, mainly nausea. Other common adverse effects include injection site reactions, headache, and nasopharyngitis, but these effects do not usually result in discontinuation of the drug. Current evidence shows that GLP-1 receptor agonists have no negative effects on the cardiovascular risk of patients with T2D. Thus, GLP-1 receptor agonists appear to have a favorable safety profile, but ongoing trials will further assess their cardiovascular effects. The aim of this review is to analyze critically the available data regarding adverse events of GLP-1 receptor agonists in different anatomic systems published in Pubmed and Scopus. Whenever possible, certain differences between GLP-1 receptor agonists are described. The review also provides the reader with structured data that compare the rates of the most common adverse effects for each of the various GLP-1 receptor agonists.
Topics: Animals; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Gastrointestinal Diseases; Glucagon-Like Peptide-1 Receptor; Humans; Hypoglycemic Agents; Kidney Diseases; Pancreatitis
PubMed: 26177483
DOI: 10.1900/RDS.2014.11.202 -
Indian Journal of Pediatrics Dec 2001Acute respiratory infections accounts for 20-40% of outpatient and 12-35% of inpatient attendance in a general hospital. Upper respiratory tract infections including... (Review)
Review
Acute respiratory infections accounts for 20-40% of outpatient and 12-35% of inpatient attendance in a general hospital. Upper respiratory tract infections including nasopharyngitis, pharyngitis, tonsillitis and otitis media constitute 87.5% of the total episodes of respiratory infections. The vast majority of acute upper respiratory tract infections are caused by viruses. Common cold is caused by viruses in most circumstances and does not require antimicrobial agent unless it is complicated by acute otitis media with effusion, tonsillitis, sinusitis, and lower respiratory tract infection. Sinusitis is commonly associated with common cold. Most instances of rhinosinusitis are viral and therefore, resolve spontaneously without antimicrobial therapy. The most common bacterial agents causing sinusitis are S. pneumoniae, H. influenzae, M. catarrhalis, S. aureus and S. pyogenes. Amoxycillin is antibacterial of choice. The alternative drugs are cefaclor or cephalexin. The latter becomes first line if sinusitis is recurrent or chronic. Acute pharyngitis is commonly caused by viruses and does not need antibiotics. About 15% of the episodes may be due to Group A beta hemolytic streptococcus (GABS). Early initiation of antibiotics in pharyngitis due to GABS can prevent complications such as acute rheumatic fever. The drug of choice is penicillin for 10-14 days. The alternative medications include oral cephalosporins (cefaclor, cephalexin), amoxicillin or macrolides.
Topics: Anti-Bacterial Agents; Child; Common Cold; Humans; India; Pharyngitis; Respiratory Tract Infections; Sinusitis
PubMed: 11838568
DOI: 10.1007/BF02722930 -
The New England Journal of Medicine Dec 2016Dupilumab, a human monoclonal antibody against interleukin-4 receptor alpha, inhibits signaling of interleukin-4 and interleukin-13, type 2 cytokines that may be... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Dupilumab, a human monoclonal antibody against interleukin-4 receptor alpha, inhibits signaling of interleukin-4 and interleukin-13, type 2 cytokines that may be important drivers of atopic or allergic diseases such as atopic dermatitis.
METHODS
In two randomized, placebo-controlled, phase 3 trials of identical design (SOLO 1 and SOLO 2), we enrolled adults with moderate-to-severe atopic dermatitis whose disease was inadequately controlled by topical treatment. Patients were randomly assigned in a 1:1:1 ratio to receive, for 16 weeks, subcutaneous dupilumab (300 mg) or placebo weekly or the same dose of dupilumab every other week alternating with placebo. The primary outcome was the proportion of patients who had both a score of 0 or 1 (clear or almost clear) on the Investigator's Global Assessment and a reduction of 2 points or more in that score from baseline at week 16.
RESULTS
We enrolled 671 patients in SOLO 1 and 708 in SOLO 2. In SOLO 1, the primary outcome occurred in 85 patients (38%) who received dupilumab every other week and in 83 (37%) who received dupilumab weekly, as compared with 23 (10%) who received placebo (P<0.001 for both comparisons with placebo). The results were similar in SOLO 2, with the primary outcome occurring in 84 patients (36%) who received dupilumab every other week and in 87 (36%) who received dupilumab weekly, as compared with 20 (8%) who received placebo (P<0.001 for both comparisons). In addition, in the two trials, an improvement from baseline to week 16 of at least 75% on the Eczema Area and Severity Index was reported in significantly more patients who received each regimen of dupilumab than in patients who received placebo (P<0.001 for all comparisons). Dupilumab was also associated with improvement in other clinical end points, including reduction in pruritus and symptoms of anxiety or depression and improvement in quality of life. Injection-site reactions and conjunctivitis were more frequent in the dupilumab groups than in the placebo groups.
CONCLUSIONS
In two phase 3 trials of identical design involving patients with atopic dermatitis, dupilumab improved the signs and symptoms of atopic dermatitis, including pruritus, symptoms of anxiety and depression, and quality of life, as compared with placebo. Trials of longer duration are needed to assess the long-term effectiveness and safety of dupilumab. (Funded by Sanofi and Regeneron Pharmaceuticals; SOLO 1 ClinicalTrials.gov number, NCT02277743 ; SOLO 2 ClinicalTrials.gov number, NCT02277769 .).
Topics: Adult; Anti-Inflammatory Agents; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Dermatitis, Atopic; Double-Blind Method; Female; Humans; Injections, Subcutaneous; Interleukin-13; Interleukin-4; Male; Middle Aged; Nasopharyngitis; Pruritus; Quality of Life
PubMed: 27690741
DOI: 10.1056/NEJMoa1610020 -
Primary Care Sep 2013Upper respiratory infections (URIs) are infections of the mouth, nose, throat, larynx (voice box), and trachea (windpipe). This article outlines the epidemiology,... (Review)
Review
Upper respiratory infections (URIs) are infections of the mouth, nose, throat, larynx (voice box), and trachea (windpipe). This article outlines the epidemiology, etiology, diagnosis, and management of URIs, including nasopharyngitis (common cold), sinusitis, pharyngitis, laryngitis, and laryngotracheitis.
Topics: Analgesics; Anti-Bacterial Agents; Histamine Antagonists; Humans; Laryngitis; Nasal Decongestants; Pharyngitis; Primary Health Care; Respiratory Tract Infections; Risk Factors; Sinusitis; United States
PubMed: 23958368
DOI: 10.1016/j.pop.2013.06.004 -
Drugs Mar 2019Secukinumab (Cosentyx), a first-in-class fully human monoclonal antibody against interleukin-17A, is approved in several countries, including the USA and those of the... (Review)
Review
Secukinumab (Cosentyx), a first-in-class fully human monoclonal antibody against interleukin-17A, is approved in several countries, including the USA and those of the EU, for the treatment of ankylosing spondylitis (AS). Subcutaneous secukinumab significantly improved the clinical signs and symptoms of AS versus placebo in three of four phase III trials. The benefits of secukinumab were generally seen regardless of whether patients had or had not received previous tumour necrosis factor (TNF) inhibitor therapy, and were sustained during longer-term (up to 5 years) treatment. Secukinumab was also associated with improvements in spinal mobility, physical function, health-related quality of life and work productivity in some of the trials. In MEASURE 1, secukinumab reduced inflammation in the sacroiliac joint, and slowed radiographic progression. Secukinumab was generally well tolerated during up to 5 years' treatment; the most commonly reported adverse event was nasopharyngitis. In the minority of patients who developed anti-drug antibodies (ADAs), ADAs did not decrease efficacy or increase adverse events. In conclusion, secukinumab is an effective therapy for TNF inhibitor-naive patients with active AS, and provides a useful treatment option for patients who have an inadequate response to or are intolerant of TNF inhibitors.
Topics: Anti-Inflammatory Agents; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antirheumatic Agents; Clinical Trials, Phase III as Topic; Humans; Immunotherapy; Interleukin-17; Multicenter Studies as Topic; Quality of Life; Randomized Controlled Trials as Topic; Sacroiliac Joint; Spine; Spondylitis, Ankylosing
PubMed: 30793255
DOI: 10.1007/s40265-019-01075-3 -
Expert Review of Clinical Immunology Sep 2018Psoriasis and psoriatic arthritis (PsA) are inflammatory immune-mediated conditions which can cause considerable disability and reduced quality of life. Management can... (Review)
Review
Psoriasis and psoriatic arthritis (PsA) are inflammatory immune-mediated conditions which can cause considerable disability and reduced quality of life. Management can be complex as clinical heterogeneity may lead to different treatment pathways. Tofacitinib is a novel, oral Janus Kinase (JAK) inhibitor with proven efficacy in rheumatoid arthritis. Areas covered: This review analyzes recent studies of tofacitinib in psoriatic disease treatment. The relevant literature was identified using clinicaltrials.gov, PubMed, and Google Scholar. Tofacitinib efficacy was demonstrated in PsA by the OPAL Broaden and OPAL Beyond phase-III studies, and received FDA and EMA approval. Tofacitinib was superior to placebo for the treatment of moderate-to-severe plaque psoriasis in the OPT Pivotal 1 and 2, OPT Retreatment studies, but FDA approval was declined for this indication based on issues of clinical efficacy and long-term safety. Expert commentary: Tofacitinib is an important oral drug for the treatment of PsA. However, the long-term safety data require further evaluation. Tofacitinib and other JAK inhibitors show potential to broaden the treatment options in PsA and other inflammatory conditions.
Topics: Antirheumatic Agents; Arthritis, Psoriatic; Clinical Trials as Topic; Drug Approval; Humans; Janus Kinases; Nasopharyngitis; Piperidines; Protein Kinase Inhibitors; Psoriasis; Pyrimidines; Pyrroles
PubMed: 30118353
DOI: 10.1080/1744666X.2018.1512404 -
Journal of Crohn's & Colitis Aug 2022The UNIFI long-term extension [LTE] study reports the efficacy and safety of subcutaneous 90 mg ustekinumab through 3 years of maintenance therapy. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND AND AIMS
The UNIFI long-term extension [LTE] study reports the efficacy and safety of subcutaneous 90 mg ustekinumab through 3 years of maintenance therapy.
METHODS
Patients randomised to ustekinumab every 12 weeks [q12w] or every 8 weeks [q8w] at maintenance baseline [N = 348] and randomised ustekinumab-treated patients in the LTE [N = 284] were evaluated. Symptomatic remission [Mayo stool frequency = 0/1, rectal bleeding = 0] was assessed. Safety included all LTE patients [N = 188 placebo and N = 457 ustekinumab].
RESULTS
Among patients randomised to the ustekinumab q12w and q8w groups at maintenance baseline, 54.1% and 56.3% achieved symptomatic remission at Week 152, respectively. Overall, 20% of patients discontinued ustekinumab, 10% of biologic-naïve and 30% of biologic-exposed patients. Among patients in symptomatic remission at Year 3, 94.6% and 98.0% of patients were also corticosteroid free, respectively. Corticosteroid-free symptomatic remission rates in the ustekinumab q12w and q8w groups were 51.2% and 55.1% at Week 152, respectively. Remission rates were higher for biologic-naïve patients than for those with a history of biologic failure. Biochemical evidence of response was demonstrated by stable, decreased C-reactive protein and faecal calprotectin measurements over 3 years. From Weeks 96 to 156, no deaths, major adverse cardiovascular events, or tuberculosis occurred. Nasopharyngitis, ulcerative colitis, and upper respiratory tract infection were most frequently reported. One ustekinumab-treated patient with a history of basal cell carcinoma [BCC] reported two BCCs. One patient in the q8w ustekinumab group, who was receiving concomitant 6-mercaptopurine, experienced serious adverse events of neutropenic sepsis and oral herpes.
CONCLUSIONS
Efficacy of ustekinumab in patients with ulcerative colitis was confirmed through 3 years. No new safety signals were observed.
Topics: Biological Products; Colitis, Ulcerative; Humans; Remission Induction; Treatment Outcome; Ustekinumab
PubMed: 35239968
DOI: 10.1093/ecco-jcc/jjac030 -
Dermatology and Therapy Mar 2023Janus kinase (JAK) inhibitors are disease-modifying agents with efficacy in treating a spectrum of burdensome dermatologic conditions. The US Food and Drug... (Review)
Review
Janus kinase (JAK) inhibitors are disease-modifying agents with efficacy in treating a spectrum of burdensome dermatologic conditions. The US Food and Drug Administration (FDA) recently placed a black box warning on this class of medications due to safety concerns based on data from studies investigating tofacitinib in patients with rheumatoid arthritis. Here we provide an overview of the timeline of FDA approval of JAK inhibitors in dermatology. We also discuss the available safety profiles of approved oral JAK1 inhibitors, namely abrocitinib and upadacitinib, oral baricitinib, a JAK1/2 inhibitor, deucravacitinib, a Tyk2 inhibitor, and the topical JAK1/2 inhibitor ruxolitinib in dermatology patients. Additionally, we offer suggestions for initial screening and laboratory monitoring for patients receiving JAK inhibitors. We found that the rates of venous thromboembolism reported in trials ranged from no events to 0.1-0.5% in dermatology-specific phase 3 clinical trials compared with no events in the placebo. The rates of cardiovascular events ranged from no events to 0.4-1.2% compared with no events to 0.5-1.2% in the placebo. The rates of serious infections were 0.4-4.8% compared with no events to 0.5-1.3% in the placebo. The rates of nonmelanoma skin cancer (NMSC) ranged from no event to 0.6-0.9% compared with no events in the placebo. The rates of non-NMSC ranged from no event to 0.2-0.7% compared with no event to 0.6% in the placebo. Most patients who developed these adverse events had risk factors for the specific event. The most common adverse events of oral JAK inhibitors included upper respiratory infections, nasopharyngitis, nausea, headache, and acne. Dermatologists should consider patients' baseline risk factors for developing serious complications when prescribing oral JAK inhibitors.
PubMed: 36790724
DOI: 10.1007/s13555-023-00892-5 -
Drugs Jan 2022Ofatumumab (Kesimpta) is a fully human anti-CD20 monoclonal antibody that can be self-administered by patients and is approved in several countries worldwide for the... (Review)
Review
Ofatumumab (Kesimpta) is a fully human anti-CD20 monoclonal antibody that can be self-administered by patients and is approved in several countries worldwide for the treatment of relapsing forms of multiple sclerosis (MS). In two identical phase III trials in adults with relapsing forms of MS, subcutaneous ofatumumab was more effective than oral teriflunomide in reducing the annualized relapse rate, as well as reducing MRI-detected lesion activity and limiting worsening of disability. Ofatumumab had a generally manageable tolerability profile; the most common adverse events (AEs) included nasopharyngitis, headache, upper respiratory tract infections and urinary tract infections. AEs of special interest (AESIs) included infections and injection-related reactions, which were generally manageable. There was no apparent association between changes in immunoglobulin G or M levels and the risk of serious infections after 3.5 years of ofatumumab treatment. Thus, ofatumumab is a convenient treatment option that is effective and has a generally manageable tolerability profile in adults with relapsing forms of MS.
Topics: Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Clinical Trials as Topic; Humans; Multiple Sclerosis, Relapsing-Remitting
PubMed: 34897575
DOI: 10.1007/s40265-021-01650-7 -
Journal of the American Academy of... Aug 2022Abrocitinib efficacy by prior dupilumab response status in patients with moderate-to-severe atopic dermatitis has not previously been assessed in phase 3 studies. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Abrocitinib efficacy by prior dupilumab response status in patients with moderate-to-severe atopic dermatitis has not previously been assessed in phase 3 studies.
OBJECTIVE
Examine efficacy and safety of abrocitinib among patients who received prior dupilumab.
METHODS
Patients with moderate-to-severe atopic dermatitis received abrocitinib 200 mg or 100 mg once daily in JADE EXTEND (phase 3 extension) after dupilumab in double-blind, placebo-controlled phase 3 JADE COMPARE.
RESULTS
Among prior dupilumab responders, ≥75% improvement in Eczema Area and Severity Index was achieved in 93.5% and 90.2% of patients who received 12 weeks of abrocitinib 200 mg and 100 mg, respectively; ≥4-point improvement in Peak Pruritus Numerical Rating Scale was achieved in 89.7% and 81.6%, respectively. Among prior dupilumab nonresponders, ≥75% improvement in Eczema Area and Severity Index was achieved with abrocitinib 200 mg and 100 mg in 80.0% and 67.7% and ≥4-point improvement in Peak Pruritus Numerical Rating Scale in 77.3% and 37.8%, respectively. Most common adverse events among abrocitinib-treated patients were nasopharyngitis, nausea, acne, and headache. Conjunctivitis occurred less frequently with abrocitinib in comparison to prior dupilumab.
LIMITATIONS
Short-term, 12-week analysis; no placebo arm.
CONCLUSION
Efficacy and safety profile of abrocitinib in JADE EXTEND supports the role of abrocitinib as a treatment for patients with moderate-to-severe atopic dermatitis, regardless of prior dupilumab response status.
Topics: Adult; Antibodies, Monoclonal, Humanized; Dermatitis, Atopic; Double-Blind Method; Eczema; Humans; Injections, Subcutaneous; Pruritus; Pyrimidines; Severity of Illness Index; Sulfonamides; Treatment Outcome
PubMed: 35439608
DOI: 10.1016/j.jaad.2022.04.009