Anti-interleukin-23 for psoriasis in elderly patients: guselkumab, risankizumab and tildrakizumab in real-world practice.

BACKGROUND: Elderly patients (aged ≥ 65 years) represent an increasing proportion of patients with psoriasis and 15% of these have moderate to severe disease. Biologics are being used frequently in this group of patients even though safety and efficacy data are limited. In addition, owing to anti-interleukin (IL)-23 therapies being a relatively recent option, no data have been reported about their use in elderly patients with psoriasis. AIM: To evaluate and compare the safety and efficacy of guselkumab, risankizumab and tildrakizumab in real-world practice in elderly patients. METHODS: This was a single-centre retrospective study that enrolled patients aged ≥ 65 years with moderate to severe plaque psoriasis, treated with guselkumab, risankizumab or tildrakizumab. The length of the study for each group depended on the drug (44 weeks for risankisumab, 40 weeks for guselkumab and 28 weeks for tildrakizumab, owing to its more recent availability in Italy). RESULTS: In total, 34 patients were enrolled (n = 20 on guselkumab; n = 8 on risankizumab; n = 6 on tildrakizumab). At Week 4, 29.4% reached 90% improvement in Psoriasis Area and Severity Index (PASI90) and 8.8% reached 100% improvement in PASI (PASI100); at Week 28, PASI90 and PASI100 was reached by 58.8% and 29.4%, respectively. At the final follow-up (Week 40 or 44, depending on drug), data were available only for the risankizumab (Week 40) and guselkumab (Week 44) and groups, and showed that 71.4% of patients had reached PASI90 and 53.5% had reached PASI100. Four patients (11.7%) discontinued treatment. No significant differences were found between the three groups. The limitations of the study included its retrospective nature of the study, small sample size, and different numbers of patients and follow-up duration for the different groups (highest for guselkumab, lowest for tildrakizumab). CONCLUSION: The three anti-IL-23 therapies assessed are promising, safe and effective options in elderly patients, and there was no significant difference between them. However, more data are needed to confirm our results and to understand their role in the management of this group of patients.

Real-life efficacy and safety of secukinumab in elderly patients with psoriasis over a 2-year period.

BACKGROUND: The prevalence of psoriasis is increasing among older people. Elderly patients with psoriasis represent a challenge for dermatologists owing to multiple comorbidities, polypharmacy and immune senescence, which lead to an increased possibility of adverse events (AEs), drug interactions and susceptibility to cancers and infections. Therefore, conventional systemic therapies are often contraindicated, with biologics appearing as the mainstay for moderate-to-severe disease. However, the data on efficacy and safety of biologics in older people are scant. AIM: To evaluate the efficacy and safety of secukinumab in elderly patients with psoriasis over a 2-year period. METHODS: A real-life retrospective observational study was performed on patients aged ≥ 65 years with moderate-to-severe plaque psoriasis who were treated with secukinumab at the Psoriasis Care Unit of the University of Naples Federico II, Italy from June 2016 to June 2019. RESULTS: Mean Psoriasis Area Severity Index (PASI) reduced from 11.4 ± 6.3 at baseline to 2.1 ± 1.7 at week 24 and 1.7 ± 1.9 at week 96 (P < 0.001 for all follow-up visits), with a final mean PASI reduction of 85.1%. A similar trend was noted for body surface area (BSA), with baseline value of 27.5 ± 15.7 decreasing to 6.8 ± 5.0 at week 24, and to 3.3 ± 2.5 at week 96 (P < 0.001 at all follow-up visits), with a final mean BSA score reduction of 88.0%. Registered AEs did not lead to secukinumab discontinuation, except in one patient (3.4%). CONCLUSION: Secukinumab seems to be a safe and effective treatment for elderly patients with psoriasis, who frequently have multiple comorbidities, polypharmacy and multiple failures with previous systemic treatments including biologics.

Essential Role of the cVRG in the Generation of Both the Expiratory and Inspiratory Components of the Cough Reflex.

As stated by Korpás and Tomori (1979), cough is the most important airway protective reflex which provides airway defensive responses to nociceptive stimuli. They recognized that active expiratory efforts, due to the activation of caudal ventral respiratory group (cVRG) expiratory premotoneurons, are the prominent component of coughs. Here, we discuss data suggesting that neurons located in the cVRG have an essential role in the generation of both the inspiratory and expiratory components of the cough reflex. Some lines of evidence indicate that cVRG expiratory neurons, when strongly activated, may subserve the alternation of inspiratory and expiratory cough bursts, possibly owing to the presence of axon collaterals. Of note, experimental findings such as blockade or impairment of glutamatergic transmission to the cVRG neurons lead to the view that neurons located in the cVRG are crucial for the production of the complete cough motor pattern. The involvement of bulbospinal expiratory neurons seems unlikely since their activation affects differentially expiratory and inspiratory muscles, while their blockade does not affect baseline inspiratory activity. Thus, other types of cVRG neurons with their medullary projections should have a role and possibly contribute to the fine tuning of the intensity of inspiratory and expiratory efforts.

Comparison between the effects of lisinopril and losartan on the cougn reflex in anesthetized and awake rabbits.

The aim of the present study was to analyze differences in cough induction between losartan and lisinopril in both anaesthetized and awake rabbits, i.e., under conditions in which the influences of higher brain areas on the cough reflex are strongly reduced or abolished. Losartan (500 µg/kg), lisinopril (100 µg/kg) and NaCl 0.9% saline solution (vehicle) were administered by intravenous injections. Animals were randomly assigned to the different experimental treatments. The cough reflex was induced by chemical (citric acid) and/or mechanical stimulation of the tracheobronchial tree. In anaesthetized rabbits, losartan and lisinopril caused similar hypotensive effects. Lisinopril, but not losartan, increased the cough response induced by both mechanical and chemical stimulation due to increases in the cough number, i.e. the number of coughs induced by each stimulation challenge. In awake animals, only lisinopril significantly increased the cough number. The results support the notion that cough potentiation induced by losartan, and possibly other sartans, is lower than that induced by most angiotensin-converting enzyme inhibitors despite the reduction or complete absence of higher brain functions. In this connection, the comparison between present results and our previous findings on ramipril and zofenopril shows that losartan and zofenopril display similar cough-inducing potency, much lower than that of lisinopril and ramipril.

Role of neurokinin receptors and ionic mechanisms within the respiratory network of the lamprey.

We have suggested that in the lamprey, a medullary region called the paratrigeminal respiratory group (pTRG), is essential for respiratory rhythm generation and could correspond to the pre-Bötzinger complex (pre-BötC), the hypothesized kernel of the inspiratory rhythm-generating network in mammals. The present study was performed on in vitro brainstem preparations of adult lampreys to investigate whether some functional characteristics of the respiratory network are retained throughout evolution and to get further insights into the recent debated hypotheses on respiratory rhythmogenesis in mammals, such as for instance the "group-pacemaker" hypothesis. Thus, we tried to ascertain the presence and role of neurokinins (NKs) and burst-generating ion currents, such as the persistent Na(+) current (I(NaP)) and the Ca(2+)-activated non-specific cation current (I(CAN)), described in the pre-Bötzinger complex. Respiratory activity was monitored as vagal motor output. Substance P (SP) as well as NK1, NK2 and NK3 receptor agonists (400-800 nM) applied to the bath induced marked increases in respiratory frequency. Microinjections (0.5-1 nl) of SP as well as the other NK receptor agonists (1 microM) into the pTRG increased the frequency and amplitude of vagal bursts. Riluzole (RIL) and flufenamic acid (FFA) were used to block I(NaP) and I(CAN), respectively. Bath application of either RIL or FFA (20-50 microM) depressed, but did not suppress respiratory activity. Coapplication of RIL and FFA at 50 microM abolished the respiratory rhythm that, however, was restarted by SP microinjected into the pTRG. The results show that NKs may have a modulatory role in the lamprey respiratory network through an action on the pTRG and that I(NaP) and I(CAN) may contribute to vagal burst generation. We suggest that the "group-pacemaker" hypothesis is tenable for the lamprey respiratory rhythm generation since respiratory activity is abolished by blocking both I(NaP) and I(CAN), but is restored by enhancing network excitability.