Comparative effectiveness of guselkumab in psoriatic arthritis: results from systematic literature review and network meta-analysis.
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ABSTRACT: Objective
The efficacy of the novel interleukin (IL)-23p19 inhibitor guselkumab for psoriatic arthritis (PsA) has recently been demonstrated in two phase 3 trials (DISCOVER-1 & -2) but has not been evaluated vs other targeted therapies for PsA. The objective was to compare guselkumab to targeted therapies for PsA for safety and joint and skin efficacy through network meta-analysis (NMA).Methods
A systematic literature review was conducted in January 2020 to identify randomized controlled trials. Bayesian NMAs were performed to compare treatments on American College of Rheumatology (ACR) 20/50/70 response, mean change from baseline in van der Heijde-Sharp (vdH-S) score, Psoriasis Area Severity Index (PASI) 75/90/100 response, adverse events (AEs) and serious adverse events (SAEs).Results
Twenty-six phase 3 studies evaluating 13 targeted therapies for PsA were included. For ACR 20 response, guselkumab 100 mg every 8 weeks (Q8W) was comparable to IL-17A inhibitors and subcutaneous tumor necrosis factor (TNF) inhibitors. Similar findings were observed for ACR 50 and 70. For vdH-S score, guselkumab Q8W was comparable to other agents except intravenous TNF therapies. Results for PASI 75 and PASI 90 response suggested guselkumab Q8W was better than most other agents. For PASI 100, guselkumab Q8W was comparable to other active agents. For AEs and SAEs, guselkumab Q8W ranked highly but comparative conclusions were uncertain. Similar results were observed for all outcomes for guselkumab 100 mg every four weeks.Conclusions
In this NMA, guselkumab demonstrated favorable arthritis efficacy comparable to IL-17A and subcutaneous TNF inhibitors while offering better PASI response relative to many other treatments.
SUBMITTER: Mease PJ
PROVIDER: S-EPMC8121447 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveThe IL-23 p19-subunit inhibitor guselkumab has been previously compared with other targeted therapies for PsA through network meta-analysis (NMA). The objective of this NMA update was to include new guselkumab COSMOS trial data, and two key comparators: the IL-23 inhibitor risankizumab and the Janus kinase (JAK) inhibitor upadacitinib.Material and methodsA systematic literature review was conducted to identify randomized controlled trials up to February 2021. A hand-search identified newer agents up to July 2021. Bayesian NMAs were performed to compare treatments on ACR response, Psoriasis Area and Severity Index (PASI) response, modified van der Heijde-Sharp (vdH-S) score, and serious adverse events (SAEs).ResultsFor ACR 20, guselkumab 100 mg every 8 weeks (Q8W) and every 4 weeks (Q4W) were comparable (i.e. overlap in credible intervals) to most other agents, including risankizumab, upadacitinib, subcutaneous TNF inhibitors and most IL-17A inhibitors. For PASI 90, guselkumab Q8W and Q4W were better than multiple agents, including subcutaneous TNF and JAK inhibitors. For vdH-S, guselkumab Q8W was similar to risankizumab, while guselkumab Q4W was better; both doses were comparable to most other agents. Most agents had comparable SAEs.ConclusionsGuselkumab demonstrates better skin efficacy than most other targeted PsA therapies, including upadacitinib. For vdH-S, both guselkumab doses are comparable to most treatments, with both doses ranking higher than most, including upadacitinib and risankizumab. Both guselkumab doses demonstrate comparable ACR responses to most other agents, including upadacitinib and risankizumab, and rank favourably in the network for SAEs.
| S-EPMC10070072 | biostudies-literature
Project description:To assess the comparative effectiveness and safety of novel biologic therapies in psoriatic arthritis (PsA) and to establish the position of the non-anti-tumor necrosis factor ? (TNF-?) biologic drugs in the treatment regimen of the disease. A systematic review and network meta-analysis (NMA) was conducted according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) requirements. Two investigators identified the studies, abstracted data, and assessed the risk of bias independently. The NMA was conducted for efficacy [American College of Rheumatology (ACR) criteria, ACR20 and ACR50; psoriasis area and severity index (PASI), PASI75] and safety outcomes [any adverse events (AEs) and serious adverse events (SAEs)]; treatments were ranked using the P score for each outcome. The PROSPERO registration number was 42017072200. MEDLINE/PubMed, Embase, Cochrane Library, and ClinicalTrials.gov were searched from the inception of each database to July 10, 2017. Randomized controlled trials (RCTs) for abatacept, apremilast, secukinumab or ustekinumab in adults with moderate and severe PsA were included. The overall PsA population and anti-TNF-?-naive, anti-TNF-?-failure, or anti-TNF-?-experienced subpopulations were considered. We identified eight eligible RCTs and included them in the systematic review and NMA. Significant differences in ACR20 response rate were revealed between secukinumab 150 mg and apremilast 20 mg [relative risk; RR?=?2.55 (CI-confidence interval; 1.24, 5.23)] and between secukinumab 300 mg and apremilast 20 or 30 mg [RR?=?3.57 CI (1.48, 8.64) and RR?=?2.84 CI (1.18, 6.86), respectively]. Any AEs occurred more often in apremilast 20 and 30 mg compared with placebo [RR?=?0.58 CI (0.45, 0.74) and RR?=?0.58 CI (0.45, 0.75), respectively] but also compared with secukinumab 150 mg [RR?=?0.54 CI (0.35, 0.81) and RR?=?0.45 CI (0.35, 0.82), respectively]. No significant differences were revealed for SAEs among biologics and between biologics and placebo. In the overall population, as well as in the anti-TNF-?-naive subpopulation, secukinumab at a dose of 300 and 150 mg was ranked the highest for the ACR20 endpoint, while in the anti-TNF-?-experienced subpopulation, secukinumab 300 mg and apremilast 30 mg revealed the highest rank. Secukinumab 75 mg was the safest drug in terms of any AEs, but for SEAs the safest was ustekinumab 90 mg. Our study revealed no significant differences among non-anti-TNF-? biologics in the treatment of PsA in the comparisons performed with regards to the highest efficacy and safety. Both in the overall population and in the analyzed subpopulations, secukinumab 300 mg was ranked the highest for the ACR20 response rate. Secukinumab 300 mg was the safest drug in terms of any AEs, and ustekinumab 90 mg presented the lowest overall risk of SAEs. Head-to-head trials and evaluation of comparative efficacy and safety between non-TNF-? biologics are warranted to inform clinical decision making with a relevant treatment paradigm.
| S-EPMC5773655 | biostudies-literature
Project description:IntroductionThe aim of this work is to evaluate treatment persistence and clinical outcomes after 6 months of on-label guselkumab use in patients with rheumatologist-diagnosed active psoriatic arthritis (PsA) enrolled in the CorEvitas PsA/Spondyloarthritis Registry.MethodsParticipants with PsA who initiated and persisted with on-label guselkumab use post-Food and Drug Administration (FDA) approval for active PsA (7/13/2020; subcutaneous 100 mg at weeks 0, 4, and every 8 weeks) at their 6-month follow-up visit (occurring through 3/31/2023) comprised the primary analysis population (On-Label Persisters). Hierarchical, multiplicity-controlled primary and secondary outcomes were mean (95% confidence interval) changes from baseline at 6 months in clinical Disease Activity Index for PsA (cDAPSA; primary), Physician Global Assessment (PGA) of arthritis and psoriasis (visual analog scale [VAS] 0-100), patient-reported pain (VAS 0-100), and percent body surface area with psoriasis (%BSA). Paired t tests determined changes that were statistically significantly different from 0 (α = 0.05).ResultsAmong 114 patients who initiated on-label guselkumab and had eligible baseline and 6-month visits, 90 (78.9%) had persistent use. Among these On-Label Persisters at baseline, mean duration of PsA symptoms = 13.6 years; mean cDAPSA, PGA, and patient-reported pain = 22.0, 42.3, and 57.0, respectively; 94.4% had a history of psoriasis (mean BSA 7.6%); and 18.9% and 73.3%, respectively, previously received 1 or ≥ 2 biologic/targeted synthetic disease-modifying antirheumatic drugs. The mean change (improvement) in cDAPSA was - 5.4 (- 8.5, - 2.3; p < 0.001) at 6 months. Significant mean improvements in PGA (- 19.0 [- 24.2, - 13.8]), patient-reported pain (- 9.1 [- 14.4, - 3.8]), and %BSA (- 5.1 [- 7.6, - 2.7]) were also observed (all p < 0.001).ConclusionsIn this real-world PsA population, generally characterized by longstanding, treatment-resistant, active disease at baseline, persistent guselkumab use in nearly 80% of patients with on-label use was accompanied by significant improvements in joint and skin symptoms and patient-reported pain at 6 months. These registry data support results from randomized clinical trials demonstrating the efficacy of guselkumab in improving PsA signs and symptoms.Trial registrationclinicaltrials.gov: NCT02530268.
| S-EPMC10654277 | biostudies-literature
Project description:BackgroundThe monoclonal antibody guselkumab is the first selective inhibitor of the interleukin-23 p19 subunit approved to treat adults with moderate-to-severe plaque psoriasis and active psoriatic arthritis (PsA). Given its recent approval for active PsA, data describing patients with PsA initiating guselkumab outside of clinical trials are limited.ObjectiveThis analysis describes characteristics of patients with rheumatologist-diagnosed PsA initiating guselkumab in the US-based, prospective, observational CorEvitas Psoriatic Arthritis/Spondyloarthritis Registry.MethodsDemographics, lifestyle/disease characteristics, comorbidities, prior treatment, and disease activity were summarized for patients with PsA initiating guselkumab from registry inception through 30 September, 2021.ResultsOf 113 patients initiating guselkumab, the majority were female (63%), obese (67%), had psoriasis (89%), and initiated guselkumab as monotherapy (81%). Common comorbidities were hypertension (32%), depression (30%), and diabetes mellitus (26%). Mean tender (6.8) and swollen (2.0) joint counts, clinical Disease Activity Index for PsA score (19.1), and 57% of participants with ≥ 3% body surface area affected by psoriasis indicated moderate disease activity. Axial involvement was identified in 49% of patients. Median patient-reported pain and fatigue visual analog scale scores (0-100) were 60 and 59, respectively. Prior to guselkumab, 76% of patients had received two or more biologic disease-modifying antirheumatic drugs; the last therapy prior to guselkumab was a biologic disease-modifying antirheumatic drug in 81% of patients.ConclusionsRegistry participants with PsA initiating guselkumab had active peripheral joint and skin disease, with substantial pain and fatigue; a considerable proportion had axial involvement. Future studies will evaluate the effectiveness of guselkumab in this population.
| S-EPMC9712871 | biostudies-literature
Project description:The objectives of this systematic literature review (SLR) were to identify domains and outcome measures used in psoriatic arthritis (PsA) studies in the past 5 years, and to compare the measurement of the Outcome Measures in Rheumatology (OMERACT) 2006 PsA Core Domain Set in studies published in 2010-2015 vs those published in 2006-2010. We performed a systematic literature search in two databases, PubMed and Embase, to identify randomised controlled trials (RCTs) in PsA. We also identified PsA longitudinal observational studies (LOS). Three patient research partners provided input into study conception, and data collection and interpretation. We identified 41 studies representing 22 unique RCTs, 27 LOS and 12 registries. Across all studies, we identified 24 domains and 169 outcome measures. In addition to the PsA Core Domain Set (6 domains), the following domains were also assessed in more than 30% of RCTs: acute phase reactants, dactylitis, enthesitis, fatigue and work productivity. We identified a range of 1-15 outcome measures per domain with a mean (SD) of 7 (4.7) per domain. The complete PsA Core Domain Set was assessed in 59% of RCTs in 2010-2015 compared to 23.5% RCTs in 2006-2010. There has been increased measurement of the PsA Core Domain Set in RCTs and LOS in the past 5 years. Numerous additional outcomes were also measured. The PsA Core Domain Set needs an update to standardise PsA outcome assessments. This SLR will inform the development of an updated PsA Core Domain Set with patient research partner input.
| S-EPMC4780312 | biostudies-other
Project description:Malaria causes significant morbidity and mortality worldwide. There are several preventive measures that are currently employed, including insecticide-treated nets (ITNs, including long-lasting insecticidal nets and insecticidal-treated bed nets), indoor residual spraying (IRS), prophylactic drugs (PD), and untreated nets (UN). However, it is unclear which measure is the most effective for malaria prevention. We therefore undertook a network meta-analysis to compare the efficacy of different preventive measures on incidence of malaria infection.A systematic literature review was undertaken across four medical and life sciences databases (PubMed, Cochrane Central, Embase, and Web of Science) from their inception to July 2016 to compare the effectiveness of different preventive measures on malaria incidence. Data from the included studies were analysed for the effectiveness of several measures against no intervention (NI). This was carried out using an automated generalized pairwise modeling (GPM) framework for network meta-analysis to generate mixed treatment effects against a common comparator of no intervention (NI).There were 30 studies that met the inclusion criteria from 1998-2016. The GPM framework led to a final ranking of effectiveness of measures in the following order from best to worst: PD, ITN, IRS and UN, in comparison with NI. However, only ITN (RR: 0.49, 95% CI: 0.32-0.74) showed precision while other methods [PD (RR: 0.24, 95% CI: 0.004-15.43), IRS (RR: 0.55, 95% CI: 0.20-1.56) and UN (RR: 0.73, 95% CI: 0.28-1.90)] demonstrating considerable uncertainty associated with their point estimates.Current evidence is strong for the protective effect of ITN interventions in malaria prevention. Even though ITNs were found to be the only preventive measure with statistical support for their effectiveness, the role of other malaria control measures may be important adjuncts in the global drive to eliminate malaria.
| S-EPMC5869791 | biostudies-other
Project description:To characterise the comparative effectiveness of combination therapy (a tumour necrosis factor inhibitor (TNFi) and a conventional synthetic disease-modifying antirheumatic drug (csDMARD) such as methotrexate) and monotherapy (TNFi only) for psoriatic arthritis (PsA) from a large US registry.The analysis included adult patients with PsA who were enrolled in the Corrona database (ClinicalTrials.gov, NCT01402661), had initiated a TNFi, were biologic naïve, and had a follow-up visit ?90?days after drug initiation. The endpoints of the analysis were TNFi persistence (drug survival) and time to Clinical Disease Activity Index (CDAI) remission. All analyses were performed using propensity scoring, which were estimated using CDAI and patient sex, to control for channelling bias.Of 519 patients meeting the inclusion criteria (318 with combination therapy and 201 with monotherapy), the analysis population was 497 for TNFi persistence and 380 for time to remission. The difference between combination therapy (TNFi+methotrexate, 91% of patients; TNFi+other csDMARD, 9%) and monotherapy was not statistically significant for TNFi persistence (32 and 31?months, p=0.73) and time to remission (21 and 25?months, p=0.56). Predictors of TNFi persistence included Hispanic ethnicity (longer persistence), PsA duration (longer persistence), history of methotrexate use (shorter persistence), body mass index (shorter persistence) and disease activity (shorter persistence).Patients with PsA from a large US registry experienced similar TNFi persistence on combination therapy and monotherapy. Prospective, randomised clinical trials evaluating the efficacy of combination therapy versus monotherapy would provide much-needed clarity on treatment options for patients with PsA.NCT01402661.
| S-EPMC4716450 | biostudies-literature
Project description:ObjectiveTo systematically review the accuracy and characteristics of different questionnaire-based PsA screening tools.MethodsA systematic review of MEDLINE, Excerpta Medical Database, Cochrane Central Register of Controlled Trials and Web of Science was conducted to identify studies that evaluated the accuracy of self-administered PsA screening tools for patients with psoriasis. A bivariate meta-analysis was used to pool screening tool-specific accuracy estimates (sensitivity and specificity). Heterogeneity of the diagnostic odds ratio was evaluated through meta-regression. All full-text records were assessed for risk of bias with the QUADAS 2 tool.ResultsA total of 2280 references were identified and 130 records were assessed for full-text review, of which 42 were included for synthesis. Of these, 27 were included in quantitative syntheses. Of the records, 37% had an overall low risk of bias. Fourteen different screening tools and 104 separate accuracy estimates were identified. Pooled sensitivity and specificity estimates were calculated for the Psoriatic Arthritis Screening and Evaluation (cut-off = 44), Psoriatic Arthritis Screening and Evaluation (47), Toronto Psoriatic Arthritis Screening (8), Psoriasis Epidemiology Screening Tool (3) and Early Psoriatic Arthritis Screening Questionnaire (3). The Early Psoriatic Arthritis Screening Questionnaire reported the highest sensitivity and specificity (0.85 each). The I2 for the diagnostic odds ratios varied between 76 and 90.1%. Meta-regressions were conducted, in which the age, risk of bias for patient selection and the screening tool accounted for some of the observed heterogeneity.ConclusionsQuestionnaire-based tools have moderate accuracy to identify PsA among psoriasis patients. The Early Psoriatic Arthritis Screening Questionnaire appears to have slightly better accuracy compared with the Toronto Psoriatic Arthritis Screening, Psoriasis Epidemiology Screening Tool and Psoriatic Arthritis Screening and Evaluation. An economic evaluation could model the uncertainty and estimate the cost-effectiveness of PsA screening programs that use different tools.
| S-EPMC6434376 | biostudies-literature
Project description:Background: No head-to-head studies are currently available comparing pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) with 13-valent pneumococcal conjugate vaccine (PCV-13). This study explored the feasibility of using network meta-analysis (NMA) to conduct an indirect comparison of the relative efficacy or effectiveness of the two vaccines.Methods: A systematic literature search was conducted for published randomized controlled trials (RCTs) and non-RCT studies reporting data on vaccine efficacy or effectiveness against invasive pneumococcal disease in children aged <5 years receiving 7-valent pneumococcal conjugate vaccine (PCV-7), PHiD-CV or PCV-13. Study quality was evaluated using published scales. NMA feasibility was assessed by considering whether a connected network could be constructed by examining published studies for differences in study or patient characteristics that could act as potential treatment effect modifiers or confounding variables.Results: A total of 26 publications were included; 2 RCTs (4 publications), 7 indirect cohort studies, and 14 case-control studies (15 publications). Study quality was generally good. The RCTs could not be connected in a network as there was no common comparator. The studies differed considerably in design, dose number, administration schedules, and subgroups analyzed. Reporting of exposure status and subject characteristics was inconsistent.Conclusion: NMA to compare the relative efficacy or effectiveness of PHiD-CV and PCV-13 is not feasible on the current evidence base, due to the absence of a connected network across the two RCTs and major heterogeneity between studies. NMA may be possible in future if sufficient RCTs become available to construct a connected network.
| S-EPMC6930063 | biostudies-literature
Project description:ObjectiveTo further characterize the effect of guselkumab, a selective IL-23p19-subunit inhibitor approved for PsA, on enthesitis and assess relationships between enthesitis resolution and patient status/outcomes.MethodsAdults with active PsA despite standard therapies in the phase 3 DISCOVER-1 and DISCOVER-2 studies were randomized 1:1:1 to guselkumab 100 mg every 4 weeks (Q4W); guselkumab 100 mg at week 0, week 4, Q8W; or placebo through week 20 followed by guselkumab 100 mg Q4W. Independent assessors evaluated enthesitis using the Leeds Enthesitis Index (LEI; total score 0-6). Enthesitis findings through week 24 were pre-specified to be pooled across studies; post hoc and week 52 analyses also employed pooled data.ResultsAmong 1118 randomized, treated patients in DISCOVER-1 and 2 who had ≥1 LEI site evaluated, 65% had enthesitis at baseline. These patients exhibited numerically more swollen and tender joints, systemic inflammation and impaired physical function than patients without enthesitis. Guselkumab Q4W and Q8W were superior to placebo in resolving pre-existing enthesitis at week 24 (45 and 50% vs 29%; both adjusted P = 0.0301). Enthesitis resolution rates continued to rise; 58% of guselkumab-randomized patients achieved resolution at week 52, including patients with mild (LEI = 1; 70-75%), moderate (LEI = 2; 69-73%) or severe (LEI = 3-6; 42-44%) enthesitis at baseline. Among guselkumab-randomized patients with resolved enthesitis at week 24, 42% achieved minimal disease activity at week 52, vs 17% of patients with unresolved enthesitis.ConclusionGuselkumab resulted in higher proportions of PsA patients with resolved enthesitis by week 24, with maintenance of resolution rates through 1 year. As enthesitis confers greater disease burden, sustained resolution could portend better patient outcomes.Clinical trial registrationDISCOVER 1 (NCT03162796) and DISCOVER 2 (NCT03158285).
| S-EPMC8566200 | biostudies-literature