Comparative Risk-Benefit Analysis of Different Classes of Biologic Agents in Patients with Psoriasis: A Case Study on the Pros and Cons of Mixed Treatment Comparison in Synthesizing Complex Evidence Networks

Authors

  • Mariangela Peruzzi Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy
  • Delia Colombo Novartis, Origgio, Italy
  • Isotta Chimenti Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy
  • Elena De Falco Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy
  • Antonio Abbate VCU Pauley Heart Center, Virginia Commonwealth University, Richmond, VA, USA
  • Giacomo Frati Department of AngioCardioNeurology, IRCCS NeuroMed, Pozzilli, Italy
  • Giuseppe Biondi-Zoccai Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy

DOI:

https://doi.org/10.6000/1929-6029.2014.03.03.3

Keywords:

Biologic therapy, Biologics, Meta-analysis, Mixed treatment comparison, Network meta-analysis, Plaque psoriasis, Psoriasis, Psoriatic arthritis, Systematic review

Abstract

Background: Several classes of biologic agents are used for the management of moderate to severe psoriasis or psoriatic arthritis. However, there is uncertainty on which, if any, individual class of biologics is superior in terms of efficacy and safety in comparison to the other classes or placebo. We thus exploited the corresponding evidence network with suitable statistical methods (mixed treatment comparison and network meta-analysis) to formally address this issue.

Methods: Randomized trials on biologic agents in psoriasis (including psoriatic arthritis) were systematically sought in several databases. We distinguished anti-tumor necrosis factor-α (TNF-α) agents, anti-T lymphocytes (T-cell) agents, anti-interleukin-12/23 (IL-12/23) agents, and anti-interleukin-17 (IL-17) agents. Endpoints of interest were the rates of ≥75% reduction in the Psoriasis Area and Severity Index (PASI75), of ≥20% improvement in the American College of Rheumatology core set of outcomes (ACR20), of serious adverse events (SAE), and of adverse events (AE) at the longest available non-cross-over follow-up. Random-effect methods were used to obtain network estimates for risk ratios (RR, with 95% credible intervals).

Results: A total of 58 trials with 18,508 patients were included, with 51% affected by psoriatic arthritis. After a median of 17 weeks since randomization into parallel groups, several classes of biologic agents provided higher PASI75 rates than placebo, with anti-IL-17 agents yielding the most favorable results (RR=9.53 [5.55-13.80]). Accordingly, several classes of biologic agents provided higher ACR20 rates than placebo, with anti-TNF-α agents yielding the most favorable results (RR=2.58 [2.12-3.15]). Overall, rates of SAE and AE were higher for several but not all biologic agents versus placebo, with anti-T-cell agents being associated with the most favorable results for both SAE (RR=0.97 [0.30-3.35]), and AE (RR=1.00 [0.80-1.22]).

Conclusions: Biologic agents provide significant clinical benefits in patients with moderate to severe psoriasis or psoriatic arthritis. There are differences in the efficacy and safety profile of each class, with anti-IL-17 and anti-TNF-α agents appearing most effective, and anti-T-cell agents appearing safest.

Author Biographies

Mariangela Peruzzi, Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy

Department of Medico-Surgical Sciences and Biotechnologies

Isotta Chimenti, Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy

Department of Medico-Surgical Sciences and Biotechnologies

Elena De Falco, Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy

Department of Medico-Surgical Sciences and Biotechnologies

Antonio Abbate, VCU Pauley Heart Center, Virginia Commonwealth University, Richmond, VA, USA

VCU Pauley Heart Center

Giacomo Frati, Department of AngioCardioNeurology, IRCCS NeuroMed, Pozzilli, Italy

Department of AngioCardioNeurology

Giuseppe Biondi-Zoccai, Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy

Department of Medico-Surgical Sciences and Biotechnologies

References

Menter A. The status of biologic therapies in the treatment of moderate to severe psoriasis. Cutis 2009; 84: 14-24. Available from URL: http://www.ncbi.nlm.nih.gov/pubmed/ 19916298

Mortel MR, Emer J. Prospective new biologic therapies for psoriasis and psoriatic arthritis. J Drugs Dermatol 2010; 9: 947-58. Availble from URL: http://www.ncbi.nlm.nih.gov/ pubmed/20684145

Kim IH, West CE, Kwatra SG, Feldman SR, O'Neill JL. Comparative efficacy of biologics in psoriasis: a review. Am J Clin Dermatol 2012; 13: 365-74. http://dx.doi.org/10.2165/11633110-000000000-00000 DOI: https://doi.org/10.2165/11633110-000000000-00000

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: 826-50. http://dx.doi.org/10.1016/j.jaad.2008.02.039 DOI: https://doi.org/10.1016/j.jaad.2008.02.039

Blöchl-Daum B. "Me-too drugs" and the concept of a class effect. Wien Med Wochenschr 2006; 156: 494-7. http://dx.doi.org/10.1007/s10354-006-0333-2 DOI: https://doi.org/10.1007/s10354-006-0333-2

Lin VW, Ringold S, Devine EB. Comparison of Ustekinumab With Other Biological Agents for the Treatment of Moderate to Severe Plaque Psoriasis: A Bayesian Network Meta-analysis. Arch Dermatol 2012; 148: 1403-10. http://dx.doi.org/10.1001/2013.jamadermatol.238 DOI: https://doi.org/10.1001/2013.jamadermatol.238

Migliore A, Bizzi E, Broccoli S, Laganà B. Indirect comparison of etanercept, infliximab, and adalumimab for psoriatic arthritis: mixed treatment comparison using placebo as common comparator. Clin Rheumatol 2012; 31: 193-4. http://dx.doi.org/10.1007/s10067-011-1862-7 DOI: https://doi.org/10.1007/s10067-011-1862-7

Reich K, Burden AD, Eaton JN, Hawkins NS. Efficacy of biologics in the treatment of moderate to severe psoriasis: a network meta-analysis of randomized controlled trials. Br J Dermatol 2012; 166: 179-88. http://dx.doi.org/10.1111/j.1365-2133.2011.10583.x DOI: https://doi.org/10.1111/j.1365-2133.2011.10583.x

Schmitt J, Rosumeck S, Thomaschewski G, Sporbeck B, Haufe E, Nast A. Efficacy and safety of systemic treatments for moderate-to-severe psoriasis: meta-analysis of randomized controlled trials. Br J Dermatol 2014; 170: 274-303. http://dx.doi.org/10.1111/bjd.12663 DOI: https://doi.org/10.1111/bjd.12663

Cawson MR, Mitchell SA, Knight C, Wildey H, Spurden D, Bird A, Orme ME. Systematic review, network meta-analysis and economic evaluation of biological therapy for the management of active psoriatic arthritis. BMC Musculoskelet Disord 2014; 15: 26. http://dx.doi.org/10.1186/1471-2474-15-26 DOI: https://doi.org/10.1186/1471-2474-15-26

Biondi-Zoccai G, editor. Network Meta-Analysis: Evidence Synthesis with Mixed Treatment Comparison. Hauppauge, NY: Nova Science Publishers; 2014. Available from URL: https://www.novapublishers.com/catalog/product_info.php?products_id=49896

Biondi-Zoccai G. In the kingdom of the blind, the one-eyed man is king: the case for the International Journal of Statistics in Medical Research. Int J Stats Med Res 2013; 2: i-iv. Available from URL: http://www.lifescienceglobal.com/ home/cart?view=product&id=409

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 2013 [Epub ahead of print]. http://dx.doi.org/10.1177/0962280213500185 DOI: https://doi.org/10.1177/0962280213500185

Greco T, Zangrillo A, Biondi-Zoccai G, Landoni G. Meta-analysis: pitfalls and hints. Heart Lung Vessel 2013; 5: 219-225. Available from URL: http://www.ncbi.nlm.nih.gov/ pmc/articles/PMC3868184/

Peruzzi M, Colombo D, De Falco E, Chimenti I, Abbate A, Frati G, Biondi-Zoccai G. Biologic therapy for psoriatic arthritis or moderate to severe plaque psoriasis: systematic review with pairwise and network meta-analysis. Int J Stats Med Res 2014; 3: 74-87. http://dx.doi.org/10.6000/1929-6029.2014.03.02.1 DOI: https://doi.org/10.6000/1929-6029.2014.03.02.1

Biondi-Zoccai GG, Lotrionte M, Abbate A, et al. Compliance with QUOROM and quality of reporting of overlapping meta-analyses on the role of acetylcysteine in the prevention of contrast associated nephropathy: case study. BMJ 2006; 332: 202-9. http://dx.doi.org/10.1136/bmj.38693.516782.7C DOI: https://doi.org/10.1136/bmj.38693.516782.7C

Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ 2009; 339: b2700. http://dx.doi.org/10.1136/bmj.b2700 DOI: https://doi.org/10.1136/bmj.b2700

Biondi-Zoccai GG, Agostoni P, Abbate A, Testa L, Burzotta F. A simple hint to improve Robinson and Dickersin's highly sensitive PubMed search strategy for controlled clinical trials. Int J Epidemiol 2005; 34: 224-5. http://dx.doi.org/10.1093/ije/dyh311 DOI: https://doi.org/10.1093/ije/dyh311

Kothary N, Diak IL, Brinker A, Bezabeh S, Avigan M, Dal Pan G. Progressive multifocal leukoencephalopathy associated with efalizumab use in psoriasis patients. J Am Acad Dermatol 2011; 65: 546-51. http://dx.doi.org/10.1016/j.jaad.2010.05.033 DOI: https://doi.org/10.1016/j.jaad.2010.05.033

Rustin MH. Long-term safety of biologics in the treatment of moderate-to-severe plaque psoriasis: review of current data. Br J Dermatol 2012; 167: s3-11. http://dx.doi.org/10.1111/j.1365-2133.2012.11208.x DOI: https://doi.org/10.1111/j.1365-2133.2012.11208.x

Bittl JA. Deconstructing Stent Polymers. J Am Coll Cardiol 2014; 63: 308-9. http://dx.doi.org/10.1016/j.jacc.2013.10.016 DOI: https://doi.org/10.1016/j.jacc.2013.10.016

Lowes MA, Bowcock AM, Krueger JG. Pathogenesis and therapy of psoriasis. Nature 2007; 445: 866-73. http://dx.doi.org/10.1038/nature05663 DOI: https://doi.org/10.1038/nature05663

Hsu L, Armstrong AW. Anti-drug antibodies in psoriasis: a critical evaluation of clinical significance and impact on treatment response. Expert Rev Clin Immunol 2013; 9: 949-58. http://dx.doi.org/10.1586/1744666X.2013.836060 DOI: https://doi.org/10.1586/1744666X.2013.836060

Lumley T. Network meta-analysis for indirect treatment comparisons. Stat Med 2002; 21: 2313-24. http://dx.doi.org/10.1002/sim.1201 DOI: https://doi.org/10.1002/sim.1201

Lu G, Ades AE. Combination of direct and indirect evidence in mixed treatment comparisons. Stat Med 2004; 23: 3105-24. http://dx.doi.org/10.1002/sim.1875 DOI: https://doi.org/10.1002/sim.1875

Mills EJ, Ioannidis JP, Thorlund K, Schünemann HJ, Puhan MA, Guyatt GH. How to use an article reporting a multiple treatment comparison meta-analysis. JAMA 2012; 308: 1246-53. http://dx.doi.org/10.1001/2012.jama.11228 DOI: https://doi.org/10.1001/2012.jama.11228

Puig L. Cardiovascular risk and psoriasis: the role of biologic therapy. Actas Dermosifiliogr 2012; 103: 853-62. http://dx.doi.org/10.1016/j.adengl.2012.02.004 DOI: https://doi.org/10.1016/j.adengl.2012.02.004

Downloads

Published

2014-08-05

How to Cite

Peruzzi, M., Colombo, D., Chimenti, I., Falco, E. D., Abbate, A., Frati, G., & Biondi-Zoccai, G. (2014). Comparative Risk-Benefit Analysis of Different Classes of Biologic Agents in Patients with Psoriasis: A Case Study on the Pros and Cons of Mixed Treatment Comparison in Synthesizing Complex Evidence Networks. International Journal of Statistics in Medical Research, 3(3), 231–247. https://doi.org/10.6000/1929-6029.2014.03.03.3

Issue

Section

General Articles