Summary
Psoriasis is a skin disease that causes red, scaly and itchy patches of skin all over the body.
It affects about 125 million people worldwide. As well as causing decreased quality of life, ...more widespread psoriasis often affects internal health. New drugs developed in the last few years often help people with psoriasis to achieve completely clear skin, and improve overall health.
Two of these drugs are ixekizumab (IXE) and guselkumab (GUS). IXE and GUS work in different ways, however, and some prior research showed that IXE may work faster than GUS.
In this study, researchers from the U.S.A. and Canada tested these drugs head‐to‐head, measuring speed of clearance and complete skin clearance rates over the first 12 weeks after starting drug.
People in this study received either IXE or GUS. After 12 weeks, completely clear skin was achieved by 16% more people if they were treated with IXE compared to GUS (41% of people who took IXE versus 25% of people who took GUS).
More people on IXE than GUS had 50% clearer skin after just one week and 75% clearer skin after two weeks. Itching, skin pain, and quality of life also improved faster with IXE compared to GUS. The number of patients with serious side effects was similar for IXE and GUS.
Overall, people with psoriasis who take IXE may get clear skin faster and feel better more quickly than people who take GUS.
This is a summary of the study: A head‐to‐head comparison of ixekizumab vs. guselkumab in patients with moderate‐to‐severe plaque psoriasis: 12‐week efficacy, safety and speed of response from a randomized, double‐blinded trial
Linked Article: Blauvelt et al. Br J Dermatol 2020; 182:1348–1358
Summary
Background
Patients with psoriasis value rapid and complete skin clearance. No head‐to‐head studies have focused on early responses to interleukin (IL)‐17 vs. IL‐23 inhibitors.
Objectives
To ...compare early and complete skin clearance by the IL‐17A inhibitor ixekizumab vs. the IL‐23p19 inhibitor guselkumab.
Methods
IXORA‐R, a 24‐week, randomized, double‐blinded study, enrolled adults with moderate‐to‐severe plaque psoriasis static Physician's Global Assessment of Disease (sPGA) score of ≥ 3, Psoriasis Area and Severity Index (PASI) ≥ 12, and ≥ 10% body surface area. Patients were randomized (1 : 1) to receive the approved dose of subcutaneous ixekizumab or guselkumab. Primary end point was 100% improvement in PASI (PASI 100) at week 12. Major secondary end points included other levels of improved PASI and sPGA at different time points. Comparisons were made using the Cochran–Mantel–Haenszel test with a multiple testing strategy. Nonresponder imputation was used for missing data. After the completion of the study, the final secondary end point (PASI 100 at 24 weeks) and safety data through week 24 will be reported.
Results
In total, 1027 patients were randomized. The primary end point PASI 100 at week 12 was met 215/520 ixekizumab (41%); 126/507 guselkumab (25%); P < 0·001. All major secondary end points measured up to week 12 were met, including PASI 50 at week 1 and PASI 75 at week 2. Serious adverse event frequency was 3% for each group; no new safety signals were identified.
Conclusions
Ixekizumab was superior to guselkumab for rapidly improving signs and symptoms in patients with moderate‐to‐severe plaque psoriasis by week 12. Adverse events were similar to previous ixekizumab and guselkumab studies. Compared with the IL‐23 inhibitor guselkumab, ixekizumab can offer complete skin clearance more rapidly to patients with moderate‐to‐severe plaque psoriasis.
What's already known about this topic?
Patients with plaque psoriasis desire both high levels of clearance and rapid onset of treatment effects.
Ixekizumab, a high‐affinity monoclonal antibody that selectively targets interleukin (IL)‐17A, has demonstrated greater and faster skin clearance than etanercept and ustekinumab, with consistent long‐term efficacy, safety and durability of response.
Clinical trial data and systematic reviews have suggested that IL‐17 inhibitors can improve a patient's psoriasis more rapidly than IL‐23 inhibitors.
What does this study add?
The head‐to‐head study design directly compares the efficacy and speed of response of ixekizumab and the IL‐23 inhibitor guselkumab in moderate‐to‐severe plaque psoriasis.
The primary end point was met, showing superiority of ixekizumab over guselkumab for achieving complete skin clearance at week 12.
The safety profile of ixekizumab was consistent with previous studies.
Ixekizumab can deliver patients complete skin clearance and improved quality of life more rapidly than guselkumab.
Linked Comment: Veysey. Br J Dermatol 2020; 182:1321–1322.
Plain language summary available online
Epilepsy is a common neurological condition, affecting about 4% of individuals over their lifetime. Epilepsy can be idiopathic, secondary to an underlying genetic abnormality or unknown causes, or ...acquired. Known potential causes account for about one third of epilepsy. Control of epilepsy has primarily focused on suppressing seizure activity after epilepsy has developed. An intriguing possibility is to control acquired epilepsy by preventing epileptogenesis, the process by which the brain becomes epileptic. Many laboratory models simulate human epilepsy as well as provide a system for studying epileptogenesis. The kindling model involves repeated application of subconvulsive electrical stimulation to the brain, leading to spontaneous seizures. Other models include the cortical or systemic injection of various chemicals. These models suggest that many antiepileptic drugs, from phenobarbital and valproate (valproic acid) to levetiracetam and tiagabine, have antiepileptogenic potential. Some promising other possibilities include N-methyl-D-aspartate (NMDA) or alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) antagonists as well as the neurotrophins and their receptors. Phenobarbital, phenytoin, valproate, carbamazepine and, to a very limited extent, diazepam have been evaluated in clinical trials to test whether they actually prevent epileptogenesis in humans. Results have been very disappointing. Meta-analyses of 12 different drug-condition combinations show none with significantly lower unprovoked seizure rates among those receiving the active drug. In 4 of the 12, the observed rate was actually slightly higher among treated individuals. None of the newer drugs have been evaluated in antiepileptogenesis trials. Until some drugs demonstrate a clear antiepileptogenic effect in clinical trials, the best course to reduce the incidence of epilepsy is primary prevention of the risk-increasing events--for example, wearing helmets, using seat belts, or decreasing the risk of stroke by reducing smoking.
The optimum treatment of Type II odontoid fractures in the geriatric population remains controversial. Coexisting medical conditions encountered in the elderly patient often increase operative risk ...and make cervical immobilization difficult to tolerate. Previous studies have shown increased morbidity and mortality and decreased fusion rates for Type II odontoid fractures treated with cervical orthoses in the geriatric population, whereas low morbidity and mortality rates with operative management have recently been documented. To investigate the role of surgical and nonsurgical treatment, a retrospective analysis was performed of patients with Type II odontoid fractures who were at least 65 years old and were consecutively admitted to a single medical center from 1994 to 1998. Twenty patients met inclusion criteria. In 12 patients nonsurgical management with a cervical orthosis was attempted. The nonsurgical management failed early in six patients, with one associated death. Eleven patients were treated surgically with either anterior odontoid screw fixation or posterior C1-2 transarticular screw fixation and modified Gallie fusion. Postoperatively one patient required revision of the C1-2 transarticular screws, and there was one death. In conclusion Type II odontoid fractures in this elderly population were associated with early 10% morbidity and 20% mortality rates. Nonsurgical management of Type II odontoid fractures failed early in six (50%) of 12 patients, whereas surgical treatment failed early in one of 11 (9%) patients. Both the nonsurgical and surgical treatments resulted in approximately 10% morbidity and 10% mortality rates.
We describe a set of RNA molecules that work as transcriptional activators when tethered to DNA. These RNA activating regions were found amongst a randomized set of molecules bearing variants of a 10 ...nt loop attached to an RNA stem. The various RNA activating regions all bear an identical five‐ residue sequence with an interspersed sixth residue. The result shows that although all natural activating regions characterized thus far are peptidic, this function can be served by other kinds of moieties as well.
Using a culture model of glial tumorigenesis, we identified a novel gene that was up-regulated in malignant mouse astrocytes following the loss of p53. The gene represents the murine homologue of ...pescadillo, an uncharacterized gene that is essential for embryonic development in zebrafish. Pescadillo is a strongly conserved gene containing unique structural motifs such as a BRCA1 C-terminal domain, clusters of acidic amino acids and consensus motifs for post-translational modification by SUMO-1. Pescadillo displayed a distinct spatial and temporal pattern of gene expression during brain development, being detected in neural progenitor cells and postmitotic neurons. Although it is not expressed in differentiated astrocytes in vivo, the pescadillo protein is dramatically elevated in malignant human astrocytomas. Yeast strains harboring temperature-sensitive mutations in the pescadillo gene were arrested in either G1 or G2 when grown in nonpermissive conditions, demonstrating that pescadillo is an essential gene in yeast and is required for cell cycle progression. Consistent with the latter finding, DNA synthesis was only observed in mammalian cells expressing the pescadillo protein. These results suggest that pescadillo plays a crucial role in cell proliferation and may be necessary for oncogenic transformation and tumor progression.
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