Number needed to treat for interleukin inhibitors approved for the treatment of moderate-to-severe plaque psoriasis in Italy
Background: Interleukin (IL) inhibitors achieve greater levels of efficacy than older systemic therapies. We calculated the number needed to treat (NNT) of ixekizumab compared with other IL inhibitors approved in Italy for the treatment of moderate-to-severe plaque psoriasis.
Methods: The clinical efficacy was evaluated in terms of NNT, based on the results of a recent network meta-analysis (NMA) by the Cochrane Database of Systematic Reviews. The NMA investigated many systemic and biological treatments, but this analysis compared only the efficacy of the following IL inhibitors – brodalumab, guselkumab, ixekizumab, risankizumab, secukinumab, tildrakizumab and ustekinumab – for patients with moderate-to-severe plaque psoriasis. Drugs were compared and ranked according to effectiveness considering the PASI (Psoriasis Area and Severity Index) 90 score.
Results: One-hundred and forty trials (51,749 patients) were included in the NMA. Considering the proportion of patients who achieve PASI90, ixekizumab showed the lowest NNT among all comparators (ixekizumab 2.01 [2.46-3.00]; risankizumab 2.05 [2.50-3-05]; guselkumab 2.16 [2.68-3.36]; secukinumab 2.40 [2.90-3.51]; brodalumab 2.61 [3.18-3.88]; ustekinumab 3.44 [4.12-4.95]; tildrakizumab 3.10 [4.15-5.59].
Conclusion: The findings show that ixekizumab is the most effective option (NNT) for the treatment of moderate-to-severe plaque psoriasis.
Sarac G, Koca TT, Baglan T. A brief summary of clinical types of psoriasis. North Clin Istanb. 2016;3(1):79-82. PMID:28058392
World Health Organization. Psoriasis: Report by the Secretariat. 2013; http://apps.who.int/gb/ebwha/pdf_files/EB133/B133_5-en.pdf. Accessed January 13, 2016.
Elder JT, Bruce AT, Gudjonsson JE, et al. Molecular dissection of psoriasis: integrating genetics and biology. J Invest Dermatol. 2010;130(5):1213-1226. https://doi.org/10.1038/jid.2009.319PMID:19812592
Jariwala SP. The role of dendritic cells in the immunopathogenesis of psoriasis. Arch Dermatol Res. 2007;299(8):359-366. https://doi.org/10.1007/s00403-007-0775-4 PMID:17680257
Lowes MA, Kikuchi T, Fuentes-Duculan J, et al. Psoriasis vulgaris lesions contain discrete populations of Th1 and Th17 T cells. J Invest Dermatol. 2008;128(5):1207-1211. https://doi.org/10.1038/sj.jid.5701213 PMID:18200064
Kurd SK, Troxel AB, Crits-Christoph P, Gelfand JM. The risk of depression, anxiety, and suicidality in patients with psoriasis: a population-based cohort study. Arch Dermatol. 2010;146(8):891-895. PMID:20713823
Saraceno R, Mannheimer R, Chimenti S. Regional distribution of psoriasis in Italy. J Eur Acad Dermatol Venereol. 2008;22(3):324-329. https://doi.org/10.1111/j.1468-3083.2007.02423.xPMID:18269600
Gelfand JM, Troxel AB, Lewis JD, et al. The risk of mortality in patients with psoriasis: results from a population-based study. Arch Dermatol. 2007;143(12):1493-1499. https://doi.org/10.1001/archderm.143.12.1493 PMID:18086997
Naldi L, Colombo P, Placchesi EB, et al. Study design and preliminary results from the pilot phase of the PraKtis study: self-reported diagnoses of selected skin diseases in a representative sample of the Italian population. Dermatology. 2004;208:38-42. https://doi.org/10.1159/000075044 PMID 14730235
Vena GA, Altomare G, Ayala F, et al. Incidence of psoriasis and association with comorbidities in Italy: a 5-year observational study from a national primary care database. Eur J Dermatol. 2010;20(5):593-598. PMID:20605768
Boehncke WH, Schön MP. Psoriasis. Lancet. 2015;386(9997):983-994. https://doi.org/10.1016/S0140-6736(14)61909-7 PMID:26025581
Di Meglio P, Villanova F, Nestle FO. Psoriasis. Cold Spring Harb Perspect Med. 2014;4(8):a015354. https://doi.org/10.1101/cshperspect.a015354 PMID:25085957
Menter A, Gottlieb A, Feldman SR, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 1. Overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics. J Am Acad Dermatol. 2008;58(5):826-850. https://doi.org/10.1016/j.jaad.2008.02.039 PMID:18423260
Icen M, Crowson CS, McEvoy MT, Dann FJ, Gabriel SE, Maradit Kremers H. Trends in incidence of adult-onset psoriasis over three decades: a population-based study. J Am Acad Dermatol. 2009;60(3):394-401. https://doi.org/10.1016/j.jaad.2008.10.062 PMID:19231638
Pathirana D, Ormerod AD, Saiag P, et al. European S3-guidelines on the systemic treatment of psoriasis vulgaris. J Eur Acad Dermatol Venereol. 2009;23(suppl 2):1-70. https://doi.org/10.1111/j.1468-3083.2009.03389.x PMID:19712190
Gisondi P, Altomare G, Ayala F, et al. Italian guidelines on the systemic treatments of moderate-to-severe plaque psoriasis. J Eur Acad Dermatol Venereol. 2017;31(5):774-790. https://doi.org/10.1111/jdv.14114 PMID:28244153
Naldi L. Scoring and monitoring the severity of psoriasis. What is the preferred method? What is the ideal method? Is PASI passé? facts and controversies. Clin Dermatol. 2010;28(1):67-72. https://doi.org/10.1016/j.clindermatol.2009.03.001 PMID:20082954
Spuls PI, Lecluse LL, Poulsen ML, Bos JD, Stern RS, Nijsten T. How good are clinical severity and outcome measures for psoriasis?: quantitative evaluation in a systematic review. J Invest Dermatol. 2010;130(4):933-943. https://doi.org/10.1038/jid.2009.391 PMID:20043014
Sbidian E, Chaimani A, Afach S, et al. Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis. Cochrane Database Syst Rev. 2020;1(1):CD011535. https://doi.org/10.1002/14651858.CD011535.pub3 PMID:31917873
Puig L. PASI90 response: the new standard in therapeutic efficacy for psoriasis. J Eur Acad Dermatol Venereol. 2015;29(4):645-648. https://doi.org/10.1111/jdv.12817 PMID:25370811
Strober B, Papp KA, Lebwohl M, et al. Clinical meaningfulness of complete skin clearance in psoriasis. J Am Acad Dermatol. 2016;75(1):77-82.e7. https://doi.org/10.1016/j.jaad.2016.03.026PMID:27206759
Laupacis A, Sackett DL, Roberts RS. An assessment of clinically useful measures of the consequences of treatment. N Engl J Med. 1988;318(26):1728-1733. https://doi.org/10.1056/NEJM198806303182605 PMID:3374545
Mendes D, Alves C, Batel-Marques F. Number needed to treat (NNT) in clinical literature: an appraisal. BMC Med. 2017;15(1):112. https://doi.org/10.1186/s12916-017-0875-8PMID:28571585
Cook RJ, Sackett DL. The number needed to treat: a clinically useful measure of treatment effect. BMJ. 1995;310(6977):452-454. https://doi.org/10.1136/bmj.310.6977.452 PMID:7873954
Altman DG, Schulz KF, Moher D, et al; CONSORT GROUP (Consolidated Standards of Reporting Trials). The revised CONSORT statement for reporting randomized trials: explanation and elaboration. Ann Intern Med. 2001;134(8):663-694. https://doi.org/10.7326/0003-4819-134-8-200104170-00012 PMID:11304107
Moher D, Hopewell S, Schulz KF, et al. CONSORT 2010 explanation and elaboration: updated guidelines for reporting parallel group randomised trials. BMJ. 2010;340(Mar23 1):c869. https://doi.org/10.1136/bmj.c869 PMID:20332511
Hildebrandt M, Vervölgyi E, Bender R. Calculation of NNTs in RCTs with time-to-event outcomes: a literature review. BMC Med Res Methodol. 2009;9(1):21. https://doi.org/10.1186/1471-2288-9-21 PMID:19302699
Nuovo J, Melnikow J, Chang D. Reporting number needed to treat and absolute risk reduction in randomized controlled trials. JAMA. 2002;287(21):2813-2814. https://doi.org/10.1001/jama.287.21.2813 PMID:12038920
Alonso-Coello P, Carrasco-Labra A, Brignardello-Petersen R, et al. Systematic reviews experience major limitations in reporting absolute effects. J Clin Epidemiol. 2016;72:16-26. https://doi.org/10.1016/j.jclinepi.2015.11.002 PMID:26560992
Citrome L. Relative vs. absolute measures of benefit and risk: what’s the difference? Acta Psychiatr Scand. 2010;121(2):94-102. https://doi.org/10.1111/j.1600-0447.2009.01449.xPMID:19694632
Straus SE, Glasziou P, Richardson WS, Haynes RB. Evidence-based medicine: how to practice and teach it. London: Churchill Livingstone; 2011.
Citrome L, Ketter TA. When does a difference make a difference? Interpretation of number needed to treat, number needed to harm, and likelihood to be helped or harmed. Int J Clin Pract. 2013;67(5):407-411. https://doi.org/10.1111/ijcp.12142 PMID:23574101
Mt-Isa S, Hallgreen CE, Wang N, et al; IMI-PROTECT benefit-risk participants. Balancing benefit and risk of medicines: a systematic review and classification of available methodologies. Pharmacoepidemiol Drug Saf. 2014;23(7):667-678. https://doi.org/10.1002/pds.3636PMID:24821575
Mendes D, Alves C, Batel-Marques F. Number needed to harm in the post-marketing safety evaluation: results for rosiglitazone and pioglitazone. Pharmacoepidemiol Drug Saf. 2015;24(12):1259-1270. https://doi.org/10.1002/pds.3874 PMID:26376779
Mendes D, Alves C, Batel Marques F. Testing the usefulness of the number needed to treat to be harmed (NNTH) in benefit-risk evaluations: case study with medicines withdrawn from the European market due to safety reasons. Expert Opin Drug Saf. 2016;15(10):1301-1312. https://doi.org/10.1080/14740338.2016.1217989 PMID:27467204
Greco T, Biondi-Zoccai G, Saleh O, et al. The attractiveness of network meta-analysis: a comprehensive systematic and narrative review. Heart Lung Vessel. 2015;7(2):133-142. PMID:26157739
Greco T, Landoni G, Biondi-Zoccai G, D’Ascenzo F, Zangrillo A. A Bayesian network meta-analysis for binary outcome: how to do it. Stat Methods Med Res. 2016;25(5):1757-1773. https://doi.org/10.1177/0962280213500185 PMID:23970014
Hartz SDY, Kiri SH, Schacht A, Walzer S, Dakin H. Network meta-analysis to evaluate the efficacy of ixekizumab in the treatment of moderate-to-severe psoriasis. (Poster). International Society for Pharmacoeconomics and Outcomes (ISPOR), 19th Annual European Congress; 2016.
Núñez M, Huete T, de la Cueva P, Sacristán JA, Hartz S, Dilla T. A cost-per-number needed to treat analysis assessing the efficiency of biologic drugs in moderate to severe plaque psoriasis. Actas Dermosifiliogr. 2019;110(7):546-553. https://doi.org/10.1016/j.adengl.2019.07.001 PMID:30851873
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