Discontinuing monoclonal antibodies targeting CGRP pathway after one-year treatment: an observational longitudinal cohort study

BackgroundMonoclonal antibodies anti-calcitonin gene-related peptide (mAbs anti-CGRP) pathway are effective and safe on migraine prevention. However, some drug agencies limited these treatments to one year due to their high costs. This study aimed at evaluating the effect of discontinuing mAbs anti-CGRP on monthly migraine days (MMDs) and disability in high-frequency episodic (HFEM) and chronic migraine (CM) patients.MethodsThis observational longitudinal cohort study was conducted at 10 Italian headache centres. Consecutive adult patients were followed-up for three months (F-UP1–3) after discontinuation of a one-year erenumab/galcanezumab treatment. The primary endpoint was the change in F-UP MMDs. Secondary endpoints included variation in pain intensity (Numerical Rating Scale, NRS), monthly acute medication intake (MAMI), and HIT-6 scores. We also assessed from F-UP1 to 3 the ≥50% response rate, relapse rate to CM, and recurrence of Medication Overuse (MO).ResultsWe enrolled 154 patients (72.1% female, 48.2 ± 11.1 years, 107 CM, 47 HFEM); 91 were treated with erenumab, 63 with galcanezumab. From F-UP1 to F-UP3, MMDs, MAMI, NRS, and HIT-6 progressively increased but were still lower at F-UP3 than baseline (Friedman’s analysis of rank, p < .001). In the F-UP1–3 visits, ≥50% response rate frequency did not differ significantly between CM and HFEM patients. However, the median reduction in response rate at F-UP3 was higher in HFEM (− 47.7% [25th, − 79.5; 75th,-17.0]) than in CM patients (− 25.5% [25th, − 47.1; 75th, − 3.3]; Mann-Whitney U test; p = .032). Of the 84 baseline CM patients who had reverted to episodic migraine, 28 (33.3%) relapsed to CM at F-UP1, 35 (41.7%) at F-UP2, 39 (46.4%) at F-UP3. Of the 64 baseline patients suffering of medication overuse headache ceasing MO, 15 (18.3%) relapsed to MO at F-UP1, 26 (31.6%) at F-UP2, and 30 (42.3%, 11 missing data) at F-UP3. Lower MMDs, MAMI, NRS, and HIT-6 and higher response rate in the last month of therapy characterized patients with ≥50% response rate at F-UP1 and F-UP3 (Mann-Whitney U test; consistently p < .01).ConclusionMigraine frequency and disability gradually increased after mAbs anti-CGRP interruption. Most patients did not relapse to MO or CM despite the increase in MMDs. Our data suggest to reconsider mAbs anti-CGRP discontinuation.     

IL-17 and its role in inflammatory,autoimmune, and oncological skin diseases: state of art

Recent data support the theory of the involvement of IL-17 in the pathogenesis of several chronic inflammatory skin diseases (psoriasis, atopic dermatitis, acne, hidradenitis suppurativa) and autoimmune skin diseases (alopecia areata, vitiligo, bullous diseases). Even if the role of IL-17 in inflammatory and autoimmune diseases has been reported extensively, its role in tumor is still controversial. Some reports show that Th17 cells eradicate tumors, while others reveal that they promote the initiation and early growth of tumors. Herein, we review the role of IL-17 in the involvement of some common dermatologic diseases: psoriasis, atopic dermatitis, hidradenitis suppurativa, acne, vitiligo, melanoma, and nonmelanoma skin cancers.     

Use of biological drugs in patients with psoriasis and psoriatic arthritis in Italy: Results from the PSONG survey

This Italian multicenter retrospective study compared the drug survival and efficacy of different anti‐TNF agents in psoriasis (PsO) and psoriatic arthritis (PsA) patients. A database of PsO/PsA patients treated with adalimumab, etanercept, and infliximab from May 2013 to May 2014 was analyzed. PASI 75, 90, and 100 was calculated at each time point to evaluate efficacy. Drug survival rate and probability of maintaining PASI response were evaluated. The impact of dependent variables on probability of PASI 75 loss was evaluated by logistic regression. 1,235 patients were included, 577 with PsO and 658 with PsA. Highest survival rates were observed with adalimumab followed by etanercept and infliximab in PsO and PsA patients. The probability of maintaining PASI response was significantly higher for adalimumab followed by infliximab. For PsO patients, the odds of losing PASI 75 was higher in etanercept‐treated patients (OR: 8.1; 95% CI: 4.2–15.6, p < .001) or infliximab (OR: 6.6; 95% CI: 2.6–16.3, p < .001) vs. adalimumab. Likewise, for PsA patients the odds of losing PASI 75 was higher in etanercept‐treated patients (OR: 2.3; 95% CI: 1.4–3.8, p = .01) or infliximab (OR: 2.2; 95% CI: 1.1–4.1, p = .018) vs. adalimumab. Adalimumab could be the best therapeutic option over other anti‐TNF agents for the treatment of PsO and PsA patients.     

Chlorpromazine protection against interleukin-1 and tumor necrosis factor-mediated activities in vivo.

Interleukin (IL-1) and tumor necrosis factor (TNF) are thought to play a key role in septic shock and inflammation. We had previously shown that chlorpromazine (CPZ) has a protective effect in various models of endotoxic shock and IL-1 toxicity. We have tested the effect of CPZ on several activities of IL-1 in vivo. CPZ (4 mg/kg) inhibited increases in serum corticosterone, triglycerides and serum amyloid A (SAA). Chlorpromazine also antagonized these same effects when they were induced by endotoxin or TNF, suggesting that this activity could be implicated in the protective effect of CPZ in various models of endotoxic shock and IL-1 lethality.     

Deoxyribonucleic acid damage in human lymphocytes after percutaneous transluminal coronary angioplasty

OBJECTIVES; We investigated the presence of oxidative deoxyribonucleic acid (DNA) damage in the peripheral lymphocytes of patients undergoing percutaneous transluminal coronary angioplasty (PTCA) by using the micronucleus test and comet assay, which are sensitive biomarkers of DNA damage. BACKGROUND; Although it has recognized that ischemia-reperfusion can induce oxidative DNA damage, its occurrence in patients undergoing PTCA has not yet been demonstrated. METHODS: Three groups of patients were enrolled: 30 patients with documented coronary heart disease who underwent elective PTCA (group I); 25 patients who underwent elective coronary angiography for diagnostic purpose (group II); and 27 healthy, age- and gender-matched subjects (group III). For each subject, the frequency of micronucleated binucleated (MNBN) cells, DNA single-strand breaks (SSBs), endonuclease III-sensitive sites, and sites sensitive to formamidopyrimidine glycosylase (FPG) were analyzed before and after diagnostic procedures. RESULTS:The mean basal values of MNBN cells (p = 0.04), DNA-SSBs (p = 0.001), endonuclease III-sensitive sites (p = 0.002), and FPG sites (p < 0.0001) were significantly higher in groups I and II than in group III. A high significant increase of MNBN cell frequency was observed in group I after the PTCA procedure (11.0 +/- 1.3 vs. 19.8 +/- 1.6, p < 0.0001), whereas no significant difference was observed in group II (10.2 +/- 1.3 vs. 12.9 +/- 1.4, p = 0.18). A significant positive correlation was observed between the increase in the MNBN cell rate and total inflation time during PTCA (R = 0.549, p = 0.0017). The levels of DNA-SSBs (11.7 +/- 1.4 vs. 26.5 +/- 3.0, p = 0.0003) and FPG sites (13.8 +/- 1.8 vs. 22.5 +/- 2.4, p = 0.01) were also higher after PTCA. CONCLUSIONS: Our results provide evidence for oxidative DNA damage after PTCA, likely related to ischemia-reperfusion injury.     

Old measures and new scores in spinal muscular atrophy patients

Introduction: A recent Rasch analysis performed on the Hammersmith Functional Motor Scale—Expanded (HFMSE) in patients with spinal muscular atrophy (SMA) identified issues impacting scale validity, redundant items, and disordered thresholds on some items. Methods: We modified the HMFSE scoring based on the Rasch analysis and on expert consensus to establish whether the traditional scoring overestimated the number of patients with changes within 2 points from baseline. Data were collected retrospectively from multicenter data sets in 255 type 2 and 3 SMA patients. Results: The mean 12‐month changes using the new and the traditional scoring system did not differ significantly (P > 0.05). The numbers of patients who improved or decreased by >2 points were also similar. Conclusions: The presence of outliers using the traditional scoring system was not due to overestimation of changes in activities that were tested bilaterally or to discrepancies in the scoring hierarchy of individual items. Muscle Nerve 52:435–437, 2015     

A naturalistic study of referred children and adolescents with obsessive-compulsive disorder

OBJECTIVE: To report on clinical features, comorbidity, and response to pharmacotherapy in children and adolescents with obsessive-compulsive disorder (OCD) naturalistically followed and treated with serotonin reuptake inhibitors (SRIs). METHOD: A consecutive series of 94 patients (65 males, 29 females, age 13.6 +/- 2.8 years), referred in the period January 2001-April 2004, diagnosed with a clinical interview (Diagnostic Interview for Children and Adolescents-Revised), and followed for 10 +/- 6 months, were included in the study. RESULTS: Contamination obsessions and washing rituals were associated with less impairment than other subtypes of OCD. Aggressive sexual obsessions and checking rituals as well as symmetry obsessions and ordering-repeating rituals were more frequently comorbid with tic disorders. According to the Clinical Global Impressions-Improvement scale (score 1 or 2), 63 subjects (67%) were responders to treatment. Nonresponders were more severely impaired and had a higher number of comorbid disorders, namely, bipolar disorder and conduct disorder (p < .05). Forty-seven patients (50%) received an SRI monotherapy, whereas the other 47 (50%) needed other medications. Patients receiving SRI monotherapy were less severely impaired; had a later onset of OCD; were at a younger age at the visit, had higher rates of depression and anxiety and lower rates of bipolar disorder, attention-deficit/hyperactivity disorder, and conduct disorder (p < .05). CONCLUSIONS: Long-term naturalistic prospective studies in pediatric patients with OCD might represent an important source of information for everyday care regarding the effectiveness of a treatment over extended periods of time under routine clinical conditions.