Comparative effectiveness of targeted immunomodulators for the treatment of moderate-to-severe plaque psoriasis: A systematic review and network meta-analysis

Loos, Anne M.; Liu, Shanshan; Segel, Celia; Ollendorf, Daniel A.; Pearson, Steven D.; Linder, Jeffrey A.

doi:10.1016/j.jaad.2018.02.027

Cited by 48 publications

(49 citation statements)

References 36 publications

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“…Our findings from the 150/90 model about the relative persistence of these drugs are generally consistent with previous work using this same definition of permissible gap 11,12 . However, these studies rank secukinumab as showing similar persistence to the TNFα inhibitors, which is inconsistent with what is known about the clinical effectiveness of these drugs 3,4 . When we switch instead to the days' supply model, we find that secukinumab offers superior persistence to ustekinumab, consistent with current meta‐analyses assessing effectiveness.…”

Section: Discussionsupporting

confidence: 75%

Medication persistence of targeted immunomodulators for plaque psoriasis: A retrospective analysis using a U.S. claims database

Hendrix

Marcum

Veenstra

2020

Pharmacoepidemiology and Drug

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Purpose Studies of medication persistence in plaque psoriasis have shown inconsistent results, likely due to differing definitions of nonpersistence and of the permissible gap between refills. Also, medication persistence information for two recently approved drugs, apremilast and ixekizumab, is limited. Methods We use the Truven Health MarketScan claims database to assess persistence for six drugs: adalimumab, apremilast, etanercept, ixekizumab, secukinumab, and ustekinumab. We define the permissible gap in three ways: 150 days for ustekinumab and 90 days for all other drugs (150/90 model); 120 days for all drugs (120 model); and twice the days' supply for all drugs (days' supply model). To estimate unadjusted persistence, we use Kaplan‐Meier curves, and a proportional hazards model to estimate the adjusted risk of non‐persistence. Results Ustekinumab is most sensitive to changes in the definition of permissible gap, likely because of its longer maintenance dosing interval. Among targeted drug‐experienced patients using ustekinumab, median persistence is 358 days (95% confidence interval: 343‐371) in the 150/90 model and 189 days (179‐199) in the days' supply model. Among targeted drug‐experienced patients, median persistence in the days' supply model is longest for ixekizumab and secukinumab at 252 (217‐301) and 222 (210‐244) days, respectively. We also find that adjusted risk of nonpersistence increases by approximately 1% per year at treatment start. Conclusion The definition of permissible gap meaningfully changes both absolute and ordinal estimates of medication persistence. Each definition has unique limitations, which should be considered when interpreting persistence data.

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Section: Discussionsupporting

confidence: 75%

Medication persistence of targeted immunomodulators for plaque psoriasis: A retrospective analysis using a U.S. claims database

Hendrix

Marcum

Veenstra

2020

Pharmacoepidemiology and Drug

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“…Systematic reviews suggest that agents targeting IL-17 may be more effective than those targeting IL-23 in patients with moderate to severe plaque psoriasis and that ixekizumab ranks among the most effective of the anti-IL antibodies. [4][5][6][7] Reviewing similar evidence based on clinical trials, NICE concluded that ixekizumab was more clinically effective than adalimumab and ustekinumab, and agreed it was likely that ixekizumab was comparable with secukinumab and infliximab, in terms of the proportion of patients achieving a 75% reduction in the Psoriasis Area and Severity Index score (PASI 75 response) after 12 weeks' treatment. 2 Direct comparative trials with ustekinumab (n=302) 8 and etanercept (two studies involving a total of 2570 patients, though not all received the licensed dose) 9 in patients with moderate to severe psoriasis have been published.…”

Section: Efficacymentioning

confidence: 99%

Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis

Sbidian

Chaimani

García‐Doval

et al. 2017

Cochrane Database of Systematic Reviews

267

309

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Our review shows that compared to placebo, the biologics ixekizumab, secukinumab, brodalumab, guselkumab, certolizumab, and ustekinumab are the best choices for achieving PASI 90 in people with moderate to severe psoriasis on the basis of moderate- to high-certainty evidence. At class level, the biologic treatments anti-IL17, anti-IL12/23, anti-IL23, and anti-TNF alpha were significantly more effective than the small molecules and the conventional systemic agents, too. This NMA evidence is limited to induction therapy (outcomes were measured between 12 to 16 weeks after randomisation) and is not sufficiently relevant for a chronic disease. Moreover, low numbers of studies were found for some of the interventions, and the young age (mean age of 44 years) and high level of disease severity (PASI 20 at baseline) may not be typical of patients seen in daily clinical practice.Another major concern is that short-term trials provide scanty and sometimes poorly reported safety data and thus do not provide useful evidence to create a reliable risk profile of treatments. Indeed, we found no significant difference in the assessed interventions and placebo in terms of SAEs. Methotrexate appeared to have the best safety profile, but as the evidence was of very low to moderate quality, we cannot be sure of the ranking. In order to provide long-term information on the safety of the treatments included in this review, it will be necessary to evaluate non-randomised studies and postmarketing reports released from regulatory agencies as well.In terms of future research, randomised trials comparing directly active agents are necessary once high-quality evidence of benefit against placebo is established, including head-to-head trials amongst and between conventional systemic and small molecules, and between biological agents (anti-IL17 versus anti-IL23, anti-IL23 versus anti-IL12/23, anti-TNF alpha versus anti-IL12/23). Future trials should also undertake systematic subgroup analyses (e.g. assessing biological-naïve patients, baseline psoriasis severity, presence of psoriatic arthritis, etc.). Finally, outcome measure harmonisation is needed in psoriasis trials, and researchers should look at the medium- and long-term benefit and safety of the interventions and the comparative safety of different agents.

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“…In recent years, the number of treatments available for moderate-to-severe psoriasis has increased, enabling dermatologists to optimize therapy for patients to achieve better outcomes (8); however, choosing between therapies can be challenging. Numerous network meta-analyses (NMAs) that have investigated psoriasis therapies over the first 10 to 16 weeks of treatment have been published (9)(10)(11)(12)(13)(14) and yet only two reviews have quantitatively assessed the long-term efficacy of psoriasis therapies: one at 6 months (15) and another at 1 year (16). Since these studies were published, four new treatments have been licensed for psoriasiscertolizumab pegol, guselkumab, tildrakizumab, and risankizumab.…”

Section: Introductionmentioning

confidence: 99%

Targeted therapies for patients with moderate-to-severe psoriasis: a systematic review and network meta-analysis of PASI response at 1 year

Yasmeen¹,

Sawyer²,

Malottki³

et al. 2020

Journal of Dermatological Treatment

102

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Purpose: To compare PASI outcomes of approved biologics and apremilast after 1 year of treatment. Methods: A systematic review identified RCTs and long-term extensions reporting PASI 75, 90, and 100 responses in adults with moderate-to-severe psoriasis. Data for analysis were modeled using a Bayesian multinomial likelihood model with probit link. Results: Twenty-eight studies reporting PASI responses were included in the network meta-analysis. Differences in study design led to a stepwise approach to synthesis, consisting of two analyses. The primary analysis included nine RCTs investigating comparative efficacy at 1 year. Results indicated risankizumab, brodalumab, and guselkumab were the most effective therapies, followed by ixekizumab and secukinumab; all demonstrated superiority to ustekinumab and etanercept. The secondary analysis extended the primary analysis with 19 further studies comparing active interventions to placebo outcomes extrapolated from induction. The interventions generating the highest PASI response were the same as the primary analysis. These therapies were more effective than apremilast, ustekinumab, adalimumab, certolizumab, etanercept, and infliximab. Conclusions: This NMA demonstrated that evaluated IL-17 and IL-23 inhibitors outperformed other biological therapies after 1 year. Risankizumab had a higher probability of achieving PASI outcomes than all other biologics, except brodalumab and guselkumab, where no significant difference could be concluded.

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Comparative effectiveness of targeted immunomodulators for the treatment of moderate-to-severe plaque psoriasis: A systematic review and network meta-analysis

Cited by 48 publications

References 36 publications

Medication persistence of targeted immunomodulators for plaque psoriasis: A retrospective analysis using a U.S. claims database

Medication persistence of targeted immunomodulators for plaque psoriasis: A retrospective analysis using a U.S. claims database

Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis

Targeted therapies for patients with moderate-to-severe psoriasis: a systematic review and network meta-analysis of PASI response at 1 year

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