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Proportion of patients achieving PASI 90, PASI 100, sPGA 0/1, and sPGA 0 at week 16 with risankizumab and placebo (study 1) and OL risankizumab (study 2). NRI analysis. AI: autoinjector; NRI: non-responder imputation; OL: open-label; PASI: Psoriasis Area Severity Index; PFS: prefilled syringe; sPGA: static physician's global assessment.
Source publication
Background:
Risankizumab is approved for treatment of moderate to severe plaque psoriasis. Availability of a patient-controlled single self-injection of risankizumab may improve adherence and long-term management of psoriasis.
Objective:
To investigate efficacy, safety, and usability of a new risankizumab 150 mg/mL formulation administered as a...
Contexts in source publication
Context 1
... (1.9% and 1.9%, respectively; both p < .001, NRI analysis, Figure 2). The sensitivity analysis supported these results (PASI 90 was 67.3% and sPGA 0/1 was 83.7% for mNRI and as-observed case analyses in the risankizumab arm). ...
Context 2
... results were also consistent with risankizumab 150 mg/ mL AI in study 2 in which 66.7% (72/108) of patients achieved PASI 90, 81.5% (88/108) achieved sPGA 0/1, 46.3% (50/108) achieved PASI 100, and 47.2% (51/108) achieved sPGA 0 at week 16 (NRI analysis, Figure 2). Compared with the NRI analyses, the proportions of patients achieving PASI 90 and sPGA 0/1 were numerically similar or higher for mNRI and as-observed case analyses (67.9% and 83.0%, respectively). ...
Context 3
... with the NRI analyses, the proportions of patients achieving PASI 90 and sPGA 0/1 were numerically similar or higher for mNRI and as-observed case analyses (67.9% and 83.0%, respectively). Of note, 84.4% of patients achieved PASI 90 and 90.9% of patients achieved sPGA clear or almost clear at week 28 in study 2 (NRI analysis, Supplemental Figure 2). The percentage change from baseline in PASI for studies 1 and 2 is shown in Table 2. Table 1. ...
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Citations
... Therefore, the results of UP0068 confirmed that the 2 mL SSy can be considered therapeutically equivalent to the approved 1 mL device, but necessitated the conduct of UP0119 to confirm bioequivalence of the AI devices; this means these studies support the use of the 2 mL SSy and AI devices [29]. Delivery of bimekizumab via a single dose self-injection device is in line with the device options for secukinumab and risankizumab, other biologic treatments for moderate to severe plaque psoriasis, which both offer an SSy and AI single dose self-injection option [56][57][58]. ...
Bimekizumab has a favourable safety profile and has demonstrated rapid and superior efficacy, compared with placebo, adalimumab, ustekinumab, and secukinumab, in treating psoriasis. A previous study demonstrated the safe and effective subcutaneous self-injection of 320 mg bimekizumab via two 1 mL (2 × 160 mg) doses using safety syringe (SSy) or auto-injector (AI) devices. Delivery of 320 mg bimekizumab via a single 2 mL self-injection could lead to an improved treatment experience for patients.
We describe the results from four studies. Two self-injection experience studies (DV0002 [n = 38] and DV0006 [n = 89], sub-studies of the phase 3 study BE BRIGHT [NCT03598790]) assessed the safe and effective self-administration of bimekizumab at week 8 and baseline, as well as patient self-injection experience and pain, in patients with moderate to severe plaque psoriasis using the 2 mL SSy or AI. Additionally, we report on two bioequivalence studies (UP0068 [n = 71] and UP0119 [n = 121]) that describe pharmacokinetic profiles for two 1 mL injections and a single 2 mL injection, delivered by SSy or AI devices in healthy participants.
All patients were able to administer safe and effective self-injections at baseline and week 8 using the different 2 mL devices, except one patient that administered an incomplete dose as a result of injection site pain that was mild. Overall, bimekizumab was generally well tolerated and all adverse device effects reported were mild and did not lead to discontinuation. Patients reported a positive self-injection experience with low pain scores (all ≤ 12.0/100). Bioequivalence was demonstrated for bimekizumab between a single 2 mL injection and two 1 mL injections, using both the SSy and AI.
The 2 mL SSy and AI devices offer patients with moderate to severe plaque psoriasis two different safe and effective options for the delivery of bimekizumab, empowering individuals to select a device on the basis of personal preference.
Graphical abstract available for this article.
ClinicalTrials.gov identifier, NCT03766685.
... For example, a strength of this drug category concerns the route of administration. Subcutaneous administration with no major concerns regarding injection site reaction increases adherence and long-term management of chronic diseases and is more tolerated than IV administration [62]. In this context, unlike anti-TNF agents, ustekinumab and risankizumab showed low rates of immunogenicity that may be related to maintenance of the response in CD and may lead to a reduced risk of infusion reactions [3,41,63]. ...
Promoting a Th17 pathogenic response, the interleukin (IL)-23 pathway is crucial in the pathophysiology of inflammatory bowel disease (IBD). With a favorable safety profile, ustekinumab, a monoclonal antibody targeting the shared p40 component of IL-12/23, is currently approved for the treatment of IBD in patients with disease refractory to corticosteroids and biologic drugs. Risankizumab, mirikizumab, and guselkumab are specific IL-23p19 antagonists tested for the treatment of Crohn’s disease (CD). However, only risankizumab currently has been approved for its treatment. Trials with guselkumab and mirikizumab are currently ongoing, with promising preliminary efficacy and safety results. In this review, we provide a summary of the current knowledge about selective IL-23 inhibitors, focusing on their positioning in the therapeutic algorithm of patients with moderate to severe CD.
Background:
CT-P47 is a candidate tocilizumab biosimilar that is currently in clinical development. We assessed the usability of CT-P47 self-administration via auto-injector (AI) in patients with rheumatoid arthritis (RA).
Research design and methods:
This was a 12-week, single-arm, open-label, multiple-dose, Phase 3 study. Patients self-injected CT-P47 (162 mg/0.9 mL) via AI at Weeks 0 and 2, and then every other week via pre-filled syringe (PFS) from Week 4 through Week 10. The primary endpoint was POST-Self-Injection Assessment Questionnaire (SIAQ) at Week 2. Efficacy, safety, and immunogenicity were also assessed.
Results:
Thirty-three patients were enrolled. Mean scores for all POST-SIAQ domains at Week 2 exceeded 8, except for 'self-confidence' (7.11) and 'satisfaction with self-injection' (7.98), indicating positive patient experiences with CT-P47 AI. Furthermore, an observer-completed checklist found that all patients successfully followed the required steps for self-injection. Efficacy, assessed by Disease Activity Score in 28 joints and its components, showed improvements from baseline to Week 12. No new safety signals were observed; the most common adverse events were leukopenia, neutropenia, and injection-site reaction, each occurring in 3 (9.1%) patients.
Conclusions:
CT-P47 self-administered using an AI showed successful usability in patients with moderate-to-severe RA.
Trial registration:
ClinicalTrials.gov identifier: NCT05725434.
The prevalence of onychomycosis in adults varies considerably between countries. Ina recent survey conducted in Italy, the prevalence of onychomycosis in subjectsaged >65 years was found to be as high as 35%. The most prevalent clinicalvariant of onychomycosis is distal and lateral subungual onychomycosis (DLSO),which affects both finger and toenails in 58–85% of cases. The fungus (usuallydermatophytes) enters the nail through the distal subungual and lateral nailgroove. The primary objective of this observational, retrospective study is toevaluate the effectiveness of Mycoclear, a medical device widely used as anantifungal in outpatient clinical practice, by the Clinical Cured Index,compared with ciclopirox, an antifungal drug commonly used as a therapeuticoption in dermatology. The data collected pertains to patients who were treatedat the Department of Dermatology at the IRCCS Azienda Ospedaliero-UniversitariaSant'Orsola in Bologna, Italy, between January 1, 2019, and April 30, 2023. Theprimary outcomes are the Investigator Global Assessment of Efficacy,mycological assessment, and healthy nail growth. In accordance with theclinical practice of the involved center, patients are evaluated using theClinical Cure Index as follows: complete cure, partial cure, or no cure.Secondary outcomes are the Patient Global Assessment of Efficacy, the PatientAssessment of Usability, and the incidence of adverse events. Included patientsare men and women aged 18 years or older with distal and lateral subungualonychomycosis (DLSO) (≤30% involvement of the nail plate of at least one of thegreat toenails) evaluated as mild to moderate following OSI. In addition,patients must have positive microscopy (direct KOH) and a positive fungalculture for dermatophytes. It is not permitted for patients to have usedsystemic antifungal agents within the previous six months or topical antifungalagents on toenails within the previous six weeks. Patients were treated for aperiod of six months, in accordance with the clinical practice of the center,and were visited at baseline, week two, four, 12, and 24 (final visit). Thecalculated sample size for the study is 40 patients per group. This study isnot funded by any grants.
For many patients including those with psoriasis, scientific manuscripts comprising clinical outcomes including psoriasis area severity index (PASI) and/or physician global assessment (PGA) may be difficult to understand. However, most patients can relate to images at baseline and follow-up, particularly for dermatological diseases. This study aimed to assess the proportion of shared clinical images in psoriasis trials. A systematic review adhering to the PRISMA guidelines was performed. The review was limited to randomized controlled trials, and among these, only investigations involving biological agents for treatment of psoriasis were included. The Embase, MEDLINE and Scopus databases were searched for eligible studies published from inception to October 26, 2021. In total, 152 studies were included. When combining these, 62,871 patients were randomized. Overall, 203 images were shared depicting 60 patients in the manuscripts yielding an overall sharing rate of 0.1%. Patient images are seldom incorporated in clinical trial manuscripts which impairs interpretation for patients. Inclusion of image material would strengthen the patients’ perspective and understanding on what treatment effects that can be expected. As such, this systematic review should be an invitation to the pharmaceutical industry, other sponsors, and editorial offices to improve easy transfer of information to patients using image data.
Deucravacitinib, a newly approved oral medication for the treatment of patients with moderate to severe plaque psoriasis, demonstrated efficacy versus apremilast and placebo in two phase 3 randomized controlled trials (RCTs). A systematic review and network meta-analysis (NMA) indirectly compared deucravacitinib with other relevant systemic biologic/nonbiologic treatments.
Online databases were searched for RCTs published through October 2021. Eligible studies were head-to-head comparisons between systemic therapies and/or placebo reporting 50%, 75%, 90%, or 100% improvement in Psoriasis Area and Severity Index (PASI) from baseline in adults with moderate to severe plaque psoriasis. Comparisons included tumor necrosis factor inhibitors, interleukin (IL)-17, IL-23, and IL 12/23 inhibitors, and systemic nonbiologics. A multinomial Bayesian NMA was used to derive estimates of the relative efficacy of deucravacitinib and other systemic therapies. Response probabilities for each treatment and corresponding 95% credible intervals (CrIs) for achieving a PASI response were calculated over short-, mid-, and long-term follow-up (weeks 10–16, 24–28, and 44–60).
The NMA included 47 RCTs. Deucravacitinib showed the highest PASI 75 response rates among nonbiologic systemic therapies across time points. Deucravacitinib PASI 75 response rate (95% CrI) over short-term follow-up was 54.1% (46.5–61.6), within the range of first-generation biologics (etanercept, 39.7% [31.6–48.3]; infliximab, 79.0% [74.0–83.5]). At mid-term follow-up, deucravacitinib PASI 75 increased to 63.3% (58.0–68.4). At long-term follow-up, deucravacitinib PASI 75 was 65.9% (58.0–73.4), comparable to first-generation biologics adalimumab (62.8%; 55.3–69.6) and ustekinumab (68.0%; 64.6–71.5).
Patients receiving deucravacitinib were more likely to achieve PASI 75 response versus apremilast and methotrexate across all time points. The long-term PASI 75 response rate for deucravacitinib was similar to those of adalimumab and ustekinumab. The approval of deucravacitinib offers patients the choice of an oral therapy with long-term efficacy similar to that of some biologics.
Background:
Psoriasis is an immune-mediated disease with either skin or joints manifestations, or both, and it has a major impact on quality of life. Although there is currently no cure for psoriasis, various treatment strategies allow sustained control of disease signs and symptoms. The relative benefit of these treatments remains unclear due to the limited number of trials comparing them directly head-to-head, which is why we chose to conduct a network meta-analysis.
Objectives:
To compare the benefits and harms of non-biological systemic agents, small molecules, and biologics for people with moderate-to-severe psoriasis using a network meta-analysis, and to provide a ranking of these treatments according to their benefits and harms.
Search methods:
For this update of the living systematic review, we updated our searches of the following databases monthly to October 2022: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase.
Selection criteria:
Randomised controlled trials (RCTs) of systemic treatments in adults over 18 years with moderate-to-severe plaque psoriasis, at any stage of treatment, compared to placebo or another active agent. The primary outcomes were: proportion of participants who achieved clear or almost clear skin, that is, at least Psoriasis Area and Severity Index (PASI) 90; proportion of participants with serious adverse events (SAEs) at induction phase (8 to 24 weeks after randomisation).
Data collection and analysis:
We conducted duplicate study selection, data extraction, risk of bias assessment, and analyses. We synthesised data using pairwise and network meta-analysis (NMA) to compare treatments and rank them according to effectiveness (PASI 90 score) and acceptability (inverse of SAEs). We assessed the certainty of NMA evidence for the two primary outcomes and all comparisons using CINeMA, as very low, low, moderate, or high. We contacted study authors when data were unclear or missing. We used the surface under the cumulative ranking curve (SUCRA) to infer treatment hierarchy, from 0% (worst for effectiveness or safety) to 100% (best for effectiveness or safety).
Main results:
This update includes an additional 12 studies, taking the total number of included studies to 179, and randomised participants to 62,339, 67.1% men, mainly recruited from hospitals. Average age was 44.6 years, mean PASI score at baseline was 20.4 (range: 9.5 to 39). Most studies were placebo-controlled (56%). We assessed a total of 20 treatments. Most (152) trials were multicentric (two to 231 centres). One-third of the studies (65/179) had high risk of bias, 24 unclear risk, and most (90) low risk. Most studies (138/179) declared funding by a pharmaceutical company, and 24 studies did not report a funding source. Network meta-analysis at class level showed that all interventions (non-biological systemic agents, small molecules, and biological treatments) showed a higher proportion of patients reaching PASI 90 than placebo. Anti-IL17 treatment showed a higher proportion of patients reaching PASI 90 compared to all the interventions. Biologic treatments anti-IL17, anti-IL12/23, anti-IL23, and anti-TNF alpha showed a higher proportion of patients reaching PASI 90 than the non-biological systemic agents. For reaching PASI 90, the most effective drugs when compared to placebo were (SUCRA rank order, all high-certainty evidence): infliximab (risk ratio (RR) 49.16, 95% CI 20.49 to 117.95), bimekizumab (RR 27.86, 95% CI 23.56 to 32.94), ixekizumab (RR 27.35, 95% CI 23.15 to 32.29), risankizumab (RR 26.16, 95% CI 22.03 to 31.07). Clinical effectiveness of these drugs was similar when compared against each other. Bimekizumab and ixekizumab were significantly more likely to reach PASI 90 than secukinumab. Bimekizumab, ixekizumab, and risankizumab were significantly more likely to reach PASI 90 than brodalumab and guselkumab. Infliximab, anti-IL17 drugs (bimekizumab, ixekizumab, secukinumab, and brodalumab), and anti-IL23 drugs except tildrakizumab were significantly more likely to reach PASI 90 than ustekinumab, three anti-TNF alpha agents, and deucravacitinib. Ustekinumab was superior to certolizumab. Adalimumab, tildrakizumab, and ustekinumab were superior to etanercept. No significant difference was shown between apremilast and two non-biological drugs: ciclosporin and methotrexate. We found no significant difference between any of the interventions and the placebo for the risk of SAEs. The risk of SAEs was significantly lower for participants on methotrexate compared with most of the interventions. Nevertheless, the SAE analyses were based on a very low number of events with very low- to moderate-certainty evidence for all the comparisons. The findings therefore have to be viewed with caution. For other efficacy outcomes (PASI 75 and Physician Global Assessment (PGA) 0/1), the results were similar to the results for PASI 90. Information on quality of life was often poorly reported and was absent for several of the interventions.
Authors' conclusions:
Our review shows that, compared to placebo, the biologics infliximab, bimekizumab, ixekizumab, and risankizumab were the most effective treatments for achieving PASI 90 in people with moderate-to-severe psoriasis on the basis of high-certainty evidence. This NMA evidence is limited to induction therapy (outcomes measured from 8 to 24 weeks after randomisation), and is not sufficient for evaluating longer-term outcomes in this chronic disease. Moreover, we found low numbers of studies for some of the interventions, and the young age (mean 44.6 years) and high level of disease severity (PASI 20.4 at baseline) may not be typical of patients seen in daily clinical practice. We found no significant difference in the assessed interventions and placebo in terms of SAEs, and the safety evidence for most interventions was very low to moderate quality. More randomised trials directly comparing active agents are needed, and these should include systematic subgroup analyses (sex, age, ethnicity, comorbidities, psoriatic arthritis). To provide long-term information on the safety of treatments included in this review, an evaluation of non-randomised studies is needed. Editorial note: This is a living systematic review. Living systematic reviews offer a new approach to review updating, in which the review is continually updated, incorporating relevant new evidence as it becomes available. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review.
Introduction:
The growing interest in subcutaneous delivery of larger single-dose volumes using handheld autoinjectors raises questions about the feasible upper limits for injection volume and rate. This review critically evaluates the literature on subcutaneous administration with dose volumes greater than 1.0 mL. In so doing, it examines how previous work has addressed limitations and considerations for designing and developing large-volume autoinjectors.
Areas covered:
This article synthesizes 31 studies on large-volume subcutaneous delivery through a systematic review process and structures their findings based on three themes critical to developing large-volume autoinjectors: injection tolerability, suitability for self-administration, and pharmacokinetic equivalence with existing dosing options. This review highlights the answers provided by previous studies and identifies promising avenues for future research.
Expert opinion:
This review finds that the literature supports the feasibility of delivering single large-dose subcutaneous volumes, providing a foundation for large-volume autoinjectors. Moreover, the review guides future research to address questions within and across themes critical to large-volume autoinjector development, helping to provide health-care professionals and patients with more effective and convenient dosing options.
Background:
Psoriasis is an immune-mediated disease with either skin or joints manifestations, or both, and it has a major impact on quality of life. Although there is currently no cure for psoriasis, various treatment strategies allow sustained control of disease signs and symptoms. The relative benefit of these treatments remains unclear due to the limited number of trials comparing them directly head-to-head, which is why we chose to conduct a network meta-analysis.
Objectives:
To compare the efficacy and safety of non-biological systemic agents, small molecules, and biologics for people with moderate-to-severe psoriasis using a network meta-analysis, and to provide a ranking of these treatments according to their efficacy and safety.
Search methods:
For this update of the living systematic review, we updated our searches of the following databases monthly to October 2021: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase.
Selection criteria:
Randomised controlled trials (RCTs) of systemic treatments in adults over 18 years with moderate-to-severe plaque psoriasis, at any stage of treatment, compared to placebo or another active agent. The primary outcomes were: proportion of participants who achieved clear or almost clear skin, that is, at least Psoriasis Area and Severity Index (PASI) 90; proportion of participants with serious adverse events (SAEs) at induction phase (8 to 24 weeks after randomisation).
Data collection and analysis:
We conducted duplicate study selection, data extraction, risk of bias assessment and analyses. We synthesised data using pairwise and network meta-analysis (NMA) to compare treatments and rank them according to effectiveness (PASI 90 score) and acceptability (inverse of SAEs). We assessed the certainty of NMA evidence for the two primary outcomes and all comparisons using CINeMA, as very low, low, moderate, or high. We contacted study authors when data were unclear or missing. We used the surface under the cumulative ranking curve (SUCRA) to infer treatment hierarchy, from 0% (worst for effectiveness or safety) to 100% (best for effectiveness or safety).
Main results:
This update includes an additional 19 studies, taking the total number of included studies to 167, and randomised participants to 58,912, 67.2% men, mainly recruited from hospitals. Average age was 44.5 years, mean PASI score at baseline was 20.4 (range: 9.5 to 39). Most studies were placebo-controlled (57%). We assessed a total of 20 treatments. Most (140) trials were multicentric (two to 231 centres). One-third of the studies (57/167) had high risk of bias; 23 unclear risk, and most (87) low risk. Most studies (127/167) declared funding by a pharmaceutical company, and 24 studies did not report a funding source. Network meta-analysis at class level showed that all interventions (non-biological systemic agents, small molecules, and biological treatments) showed a higher proportion of patients reaching PASI 90 than placebo. Anti-IL17 treatment showed a higher proportion of patients reaching PASI 90 compared to all the interventions, except anti-IL23. Biologic treatments anti-IL17, anti-IL12/23, anti-IL23 and anti-TNF alpha showed a higher proportion of patients reaching PASI 90 than the non-biological systemic agents. For reaching PASI 90, the most effective drugs when compared to placebo were (SUCRA rank order, all high-certainty evidence): infliximab (risk ratio (RR) 50.19, 95% CI 20.92 to 120.45), bimekizumab (RR 30.27, 95% CI 25.45 to 36.01), ixekizumab (RR 30.19, 95% CI 25.38 to 35.93), risankizumab (RR 28.75, 95% CI 24.03 to 34.39). Clinical effectiveness of these drugs was similar when compared against each other. Bimekizumab, ixekizumab and risankizumab showed a higher proportion of patients reaching PASI 90 than other anti-IL17 drugs (secukinumab and brodalumab) and guselkumab. Infliximab, anti-IL17 drugs (bimekizumab, ixekizumab, secukinumab and brodalumab) and anti-IL23 drugs (risankizumab and guselkumab) except tildrakizumab showed a higher proportion of patients reaching PASI 90 than ustekinumab and three anti-TNF alpha agents (adalimumab, certolizumab and etanercept). Ustekinumab was superior to certolizumab; adalimumab and ustekinumab were superior to etanercept. No significant difference was shown between apremilast and two non-biological drugs: ciclosporin and methotrexate. We found no significant difference between any of the interventions and the placebo for the risk of SAEs. The risk of SAEs was significantly lower for participants on methotrexate compared with most of the interventions. Nevertheless, the SAE analyses were based on a very low number of events with low- to moderate-certainty for all the comparisons (except methotrexate versus placebo, which was high-certainty). The findings therefore have to be viewed with caution. For other efficacy outcomes (PASI 75 and Physician Global Assessment (PGA) 0/1), the results were similar to the results for PASI 90. Information on quality of life was often poorly reported and was absent for several of the interventions.
Authors' conclusions:
Our review shows that, compared to placebo, the biologics infliximab, bimekizumab, ixekizumab, and risankizumab were the most effective treatments for achieving PASI 90 in people with moderate-to-severe psoriasis on the basis of high-certainty evidence. This NMA evidence is limited to induction therapy (outcomes measured from 8 to 24 weeks after randomisation), and is not sufficient for evaluating longer-term outcomes in this chronic disease. Moreover, we found low numbers of studies for some of the interventions, and the young age (mean 44.5 years) and high level of disease severity (PASI 20.4 at baseline) may not be typical of patients seen in daily clinical practice. We found no significant difference in the assessed interventions and placebo in terms of SAEs, and the safety evidence for most interventions was low to moderate quality. More randomised trials directly comparing active agents are needed, and these should include systematic subgroup analyses (sex, age, ethnicity, comorbidities, psoriatic arthritis). To provide long-term information on the safety of treatments included in this review, an evaluation of non-randomised studies and postmarketing reports from regulatory agencies is needed. Editorial note: This is a living systematic review. Living systematic reviews offer a new approach to review updating, in which the review is continually updated, incorporating relevant new evidence as it becomes available. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review.
