Top

American Journal of Clinical Dermatology

Published in:

30-04-2022 | Etanercept | Systematic Review

Time to Relapse After Discontinuing Systemic Treatment for Psoriasis: A Systematic Review

Authors: Marie Masson Regnault, Jason Shourick, Fatma Jendoubi, Marie Tauber, Carle Paul

Published in: American Journal of Clinical Dermatology | Issue 4/2022

Abstract

Background

The decision of when to discontinue systemic treatment after achieving remission in psoriasis is an important question. In this systematic review, we sought to evaluate time to relapse after the discontinuation of systemic treatment in psoriasis patients.

Methods

Systematic searches of PubMed, Cochrane Library, and Embase databases were performed for randomized controlled studies reporting time to relapse after discontinuation of systemic drugs in psoriasis patients. In addition, pharmaceutical companies were contacted by the authors regarding missing data from the identified publications. In each publication, the time to psoriasis relapse and the timing of drug discontinuation were carefully assessed. The level of psoriasis control at the time of drug discontinuation and the definition used for psoriasis relapse were taken into account.

Results

Thirty articles published before April 2021 were included in the systematic review. Four articles focused on conventional systemic treatments with methotrexate and/or cyclosporine, nine focused on tumor necrosis factor (TNF) antagonists, eight focused on interleukin-17 (IL-17) antagonists, eight focused on IL-12/23 or IL-23 antagonists, and one focused on tofacitinib and apremilast. Different definitions were used to define psoriasis treatment success at the time of drug discontinuation. Similarly, heterogeneous criteria were used to define psoriasis relapse. Comparison between drugs was performed indirectly (i.e. across studies) for most drugs. Considering time of 50% loss of maximum Psoriasis Area Severity Index (PASI) improvement, a shorter median time to psoriasis relapse was observed with traditional systemic treatment (~ 4 weeks) compared to biological agents (from 12 to ~ 34 weeks). When using stringent relapse criteria, such as loss of PASI 90, a longer time to relapse after treatment cessation was observed with IL-23 antagonists (21–42 weeks) versus IL-17 antagonists (7–24 weeks).

Conclusion

Biological agents are associated with a longer time to relapse than oral systemic agents after drug discontinuation. Among biologicals, IL-23 antagonists are associated with the longest time to relapse. These findings may have clinical consequences for the selection of systemic agents when intermittent treatment is necessary.

Available only for authorised users

Sbidian E, Chaimani A, Afach S, Doney L, Dressler C, Hua C, Mazaud C, Phan C, Hughes C, Riddle D, Naldi L, Garcia-Doval I, Le Cleach L. Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis. Cochrane Database Syst Rev. 2020;1: 011535. https://doi.org/10.1002/14651858.CD011535.pub3.CrossRef

Hawkes JE, Chan TC, Krueger JG. Psoriasis pathogenesis and the development of novel targeted immune therapies. J Allergy Clin Immunol. 2017;140:645–53. https://doi.org/10.1016/j.jaci.2017.07.004.CrossRefPubMedPubMedCentral

Boehncke W-H, Schön MP. Psoriasis. Lancet. 2015;386:983–94. https://doi.org/10.1016/S0140-6736(14)61909-7.CrossRefPubMed

Reich K, Mrowietz U, Radtke MA, Thaci D, Rustenbach SJ, Spehr C, Augustin M. Drug safety of systemic treatments for psoriasis: results from The German Psoriasis Registry PsoBest. Arch Dermatol Res. 2015;307:875–83. https://doi.org/10.1007/s00403-015-1593-8.CrossRefPubMedPubMedCentral

Egeberg A, Ottosen MB, Gniadecki R, Broesby-Olsen S, Dam TN, Bryld LE, Rasmussen MK, Skov L. Safety, efficacy and drug survival of biologics and biosimilars for moderate-to-severe plaque psoriasis. Br J Dermatol. 2018;178:509–19. https://doi.org/10.1111/bjd.16102.CrossRefPubMed

Papp K, Gottlieb AB, Naldi L, Pariser D, Ho V, Goyal K, Fakharzadeh S, Chevrier M, Calabro S, Langholff W, Krueger G. Safety surveillance for ustekinumab and other psoriasis treatments from the Psoriasis Longitudinal Assessment and Registry (PSOLAR). J Drugs Dermatol. 2015;14:706–14.PubMed

Masson Regnault M, Konstantinou M-P, Khemis A, Poulin Y, Bourcier M, Amelot F, Bulaï Livideanu C, Paul C. Early relapse of psoriasis after stopping brodalumab: a retrospective cohort study in 77 patients. J Eur Acad Dermatol Venereol. 2017;31:1491–6. https://doi.org/10.1111/jdv.14387.CrossRefPubMed

Okubo Y, Natsume S, Usui K, Amaya M, Tsuboi R. Low-dose, short-term ciclosporin (Neoral^®) therapy is effective in improving patients’ quality of life as assessed by Skindex-16 and GHQ-28 in mild to severe psoriasis patients. J Dermatol. 2011;38:465–72. https://doi.org/10.1111/j.1346-8138.2010.01041.x.CrossRefPubMed

Heydendael VMR, Spuls PI, Opmeer BC, de Borgie CAJM, Reitsma JB, Goldschmidt WFM, Bossuyt PMM, Bos JD, de Rie MA. Methotrexate versus cyclosporine in moderate-to-severe chronic plaque psoriasis. N Engl J Med. 2003;349:658–65. https://doi.org/10.1056/NEJMoa021359.CrossRefPubMed

10.

Ellis CN, Fradin MS, Hamilton TA, Voorhees JJ. Duration of remission during maintenance cyclosporine therapy for psoriasis. Relationship to maintenance dose and degree of improvement during initial therapy. Arch Dermatol. 1995;131:791–5.CrossRef

11.

Ho VC, Griffiths CE, Albrecht G, Vanaclocha F, León-Dorantes G, Atakan N, Reitamo S, Ohannesson A, Mørk NJ, Clarke P, Pfister P, Paul C. Intermittent short courses of cyclosporin (Neoral(R)) for psoriasis unresponsive to topical therapy: a 1-year multicentre, randomized study The PISCES Study Group. Br J Dermatol. 1999;141:283–91. https://doi.org/10.1046/j.1365-2133.1999.02977.x.CrossRefPubMed

12.

Gordon KB, Gottlieb AB, Leonardi CL, Elewski BE, Wang A, Jahreis A, Zitnik R. Clinical response in psoriasis patients discontinued from and then reinitiated on etanercept therapy. J Dermatolog Treat. 2006;17:9–17. https://doi.org/10.1080/09546630500472838.CrossRefPubMed

13.

Moore A, Gordon KB, Kang S, Gottlieb A, Freundlich B, Xia HA, Stevens SR. A randomized, open-label trial of continuous versus interrupted etanercept therapy in the treatment of psoriasis. J Am Acad Dermatol. 2007;56:598–603. https://doi.org/10.1016/j.jaad.2006.09.002.CrossRefPubMed

14.

Ortonne J-P, Taïeb A, Ormerod AD, Robertson D, Foehl J, Pedersen R, Molta C, Freundlich B. Patients with moderate-to-severe psoriasis recapture clinical response during re-treatment with etanercept. Br J Dermatol. 2009;161:1190–5. https://doi.org/10.1111/j.1365-2133.2009.09238.x.CrossRefPubMed

15.

Griffiths CEM, Strober BE, van de Kerkhof P, Ho V, Fidelus-Gort R, Yeilding N, Guzzo C, Xia Y, Zhou B, Li S, Dooley LT, Goldstein NH, Menter A, ACCEPT Study Group. Comparison of ustekinumab and etanercept for moderate-to-severe psoriasis. N Engl J Med. 2010;362:118–28. https://doi.org/10.1056/NEJMoa0810652.CrossRefPubMed

16.

Menter A, Tyring SK, Gordon K, Kimball AB, Leonardi CL, Langley RG, Strober BE, Kaul M, Gu Y, Okun M, Papp K. Adalimumab therapy for moderate to severe psoriasis: a randomized, controlled phase III trial. J Am Acad Dermatol. 2008;58:106–15. https://doi.org/10.1016/j.jaad.2007.09.010.CrossRefPubMed

17.

Papp K, Crowley J, Ortonne J-P, Leu J, Okun M, Gupta SR, Gu Y, Langley RG. Adalimumab for moderate to severe chronic plaque psoriasis: efficacy and safety of retreatment and disease recurrence following withdrawal from therapy. Br J Dermatol. 2011;164:434–41. https://doi.org/10.1111/j.1365-2133.2010.10139.x.CrossRefPubMed

18.

Gottlieb AB, Evans R, Li S, Dooley LT, Guzzo CA, Baker D, Bala M, Marano CW, Menter A. Infliximab induction therapy for patients with severe plaque-type psoriasis: a randomized, double-blind, placebo-controlled trial. J Am Acad Dermatol. 2004;51:534–42. https://doi.org/10.1016/j.jaad.2004.02.021.CrossRefPubMed

19.

Menter A, Feldman SR, Weinstein GD, Papp K, Evans R, Guzzo C, Li S, Dooley LT, Arnold C, Gottlieb AB. A randomized comparison of continuous vs. intermittent infliximab maintenance regimens over 1 year in the treatment of moderate-to-severe plaque psoriasis. J Am Acad Dermatol. 2007;56:31.e1-15. https://doi.org/10.1016/j.jaad.2006.07.017.CrossRefPubMed

20.

Reich K, Ortonne J-P, Gottlieb AB, Terpstra IJ, Coteur G, Tasset C, Mease P. Successful treatment of moderate to severe plaque psoriasis with the PEGylated Fab’ certolizumab pegol: results of a phase II randomized, placebo-controlled trial with a re-treatment extension. Br J Dermatol. 2012;167:180–90. https://doi.org/10.1111/j.1365-2133.2012.10941.x.CrossRefPubMed

21.

Rich P, Sigurgeirsson B, Thaci D, Ortonne J-P, Paul C, Schopf RE, Morita A, Roseau K, Harfst E, Guettner A, Machacek M, Papavassilis C. Secukinumab induction and maintenance therapy in moderate-to-severe plaque psoriasis: a randomized, double-blind, placebo-controlled, phase II regimen-finding study. Br J Dermatol. 2013;168:402–11. https://doi.org/10.1111/bjd.12112.CrossRefPubMed

22.

Mrowietz U, Leonardi CL, Girolomoni G, Toth D, Morita A, Balki SA, Szepietowski JC, Regnault P, Thurston H, Papavassilis C, SCULPTURE Study Group. Secukinumab retreatment-as-needed versus fixed-interval maintenance regimen for moderate to severe plaque psoriasis: a randomized, double-blind, noninferiority trial (SCULPTURE). J Am Acad Dermatol. 2015;73:27-36.e1. https://doi.org/10.1016/j.jaad.2015.04.011.CrossRefPubMed

23.

Blauvelt A, Reich K, Warren RB, Szepietowski JC, Sigurgeirsson B, Tyring SK, Messina I, Bhosekar V, Oliver J, Papavassilis C, Frueh J, Langley RGB. Secukinumab re-initiation achieves regain of high response levels in patients who interrupt treatment for moderate to severe plaque psoriasis. Br J Dermatol. 2017;177:879–81. https://doi.org/10.1111/bjd.15656.CrossRefPubMed

24.

Gordon KB, Blauvelt A, Papp KA, Langley RG, Luger T, Ohtsuki M, Reich K, Amato D, Ball SG, Braun DK, Cameron GS, Erickson J, Konrad RJ, Muram TM, Nickoloff BJ, Osuntokun OO, Secrest RJ, Zhao F, Mallbris L, Leonardi CL, UNCOVER-1 Study Group, UNCOVER-2 Study Group, UNCOVER-3 Study Group. Phase 3 trials of ixekizumab in moderate-to-severe plaque psoriasis. N Engl J Med. 2016;375:345–56. https://doi.org/10.1056/NEJMoa1512711.CrossRefPubMed

25.

Blauvelt A, Papp KA, Sofen H, Augustin M, Yosipovitch G, Katoh N, Mrowietz U, Ohtsuki M, Poulin Y, Shrom D, Burge R, See K, Mallbris L, Gordon KB. Continuous dosing versus interrupted therapy with ixekizumab: an integrated analysis of two phase 3 trials in psoriasis. J Eur Acad Dermatol Venereol. 2017;31:1004–13. https://doi.org/10.1111/jdv.14163.CrossRefPubMedPubMedCentral

26.

Papp KA, Reich K, Paul C, Blauvelt A, Baran W, Bolduc C, Toth D, Langley RG, Cather J, Gottlieb AB, Thaçi D, Krueger JG, Russell CB, Milmont CE, Li J, Klekotka PA, Kricorian G, Nirula A. A prospective phase III, randomized, double-blind, placebo-controlled study of brodalumab in patients with moderate-to-severe plaque psoriasis. Br J Dermatol. 2016;175:273–86. https://doi.org/10.1111/bjd.14493.CrossRefPubMed

27.

Papp K, Menter A, Leonardi C, Soung J, Weiss S, Pillai R, Jacobson A. Long-term efficacy and safety of brodalumab in psoriasis through 120 weeks and after withdrawal and retreatment: subgroup analysis of a randomized phase III trial (AMAGINE-1). Br J Dermatol. 2020;183:1037–48. https://doi.org/10.1111/bjd.19132.CrossRefPubMedPubMedCentral

28.

Leonardi CL, Kimball AB, Papp KA, Yeilding N, Guzzo C, Wang Y, Li S, Dooley LT, Gordon KB, PHOENIX 1 Study Investigators. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 76-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 1). Lancet. 2008;371:1665–74. https://doi.org/10.1016/S0140-6736(08)60725-4.CrossRefPubMed

29.

Blauvelt A, Leonardi CL, Gooderham M, Papp KA, Philipp S, Wu JJ, Igarashi A, Flack M, Geng Z, Wu T, Camez A, Williams D, Langley RG. Efficacy and safety of continuous risankizumab therapy vs treatment withdrawal in patients with moderate to severe plaque psoriasis. JAMA Dermatol. 2020;156:1–11. https://doi.org/10.1001/jamadermatol.2020.0723.CrossRefPubMedCentral

30.

Kimball AB, Papp KA, Reich K, Gooderham M, Li Q, Cichanowitz N, La Rosa C, Blauvelt A. Efficacy and safety of tildrakizumab for plaque psoriasis with continuous dosing, treatment interruption, dose adjustments and switching from etanercept: results from phase III studies. Br J Dermatol. 2020;182:1359–68. https://doi.org/10.1111/bjd.18484.CrossRefPubMed

31.

Warren RB, Carrascosa JM, Fumero E, Schoenenberger A, Lebwohl MG, Szepietowski JC, Reich K. Time to relapse after tildrakizumab withdrawal in patients with moderate-to-severe psoriasis who were responders at week 28: post hoc analysis through 64 weeks from reSURFACE 1 trial. J Eur Acad Dermatol Venereol. 2020. https://doi.org/10.1111/jdv.16964.CrossRefPubMedPubMedCentral

32.

Cantrell W, Lee P, Mendelsohn AM, Rozzo SJ, Liao W. Efficacy and safety of tildrakizumab 100 mg for plaque psoriasis in patients randomized to treatment continuation vs treatment withdrawal with retreatment upon relapse in reSURFACE 1. J Eur Acad Dermatol Venereol. 2021. https://doi.org/10.1111/jdv.17124.CrossRefPubMedPubMedCentral

33.

Reich K, Armstrong AW, Foley P, Song M, Wasfi Y, Randazzo B, Li S, Shen Y-K, Gordon KB. Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the treatment of patients with moderate to severe psoriasis with randomized withdrawal and retreatment: Results from the phase III, double-blind, placebo- and active comparator-controlled VOYAGE 2 trial. J Am Acad Dermatol. 2017;76:418–31. https://doi.org/10.1016/j.jaad.2016.11.042.CrossRefPubMed

34.

Gordon KB, Armstrong AW, Foley P, Song M, Shen Y-K, Li S, Muñoz-Elías EJ, Branigan P, Liu X, Reich K. Guselkumab efficacy after withdrawal is associated with suppression of serum IL-23-regulated IL-17 and IL-22 in psoriasis: VOYAGE 2 study. J Investig Dermatol. 2019;139:2437-2446.e1. https://doi.org/10.1016/j.jid.2019.05.016.CrossRefPubMed

35.

Bissonnette R, Iversen L, Sofen H, Griffiths CEM, Foley P, Romiti R, Bachinsky M, Rottinghaus ST, Tan H, Proulx J, Valdez H, Gupta P, Mallbris L, Wolk R. Tofacitinib withdrawal and retreatment in moderate-to-severe chronic plaque psoriasis: a randomized controlled trial. Br J Dermatol. 2015;172:1395–406. https://doi.org/10.1111/bjd.13551.CrossRefPubMed

36.

Papp K, Reich K, Leonardi CL, Kircik L, Chimenti S, Langley RGB, Hu C, Stevens RM, Day RM, Gordon KB, Korman NJ, Griffiths CEM. Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor, in patients with moderate to severe plaque psoriasis: Results of a phase III, randomized, controlled trial (Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis [ESTEEM] 1). J Am Acad Dermatol. 2015;73:37–49. https://doi.org/10.1016/j.jaad.2015.03.049.CrossRefPubMed

37.

Gordon KB, Foley P, Krueger JG, Pinter A, Reich K, Vender R, Vanvoorden V, Madden C, White K, Cioffi C, Blauvelt A. Bimekizumab efficacy and safety in moderate to severe plaque psoriasis (BE READY): a multicentre, double-blind, placebo-controlled, randomised withdrawal phase 3 trial. Lancet. 2021;397:475–86. https://doi.org/10.1016/S0140-6736(21)00126-4.CrossRefPubMed

38.

Lebwohl M, Rivera-Oyola R, Murrell DF. Should biologics for psoriasis be interrupted in the era of COVID-19? J Am Acad Dermatol. 2020;82:1217–8. https://doi.org/10.1016/j.jaad.2020.03.031.CrossRefPubMedPubMedCentral

39.

Kamaria M, Liao W, Koo JY. How long does the benefit of biologics last? An update on time to relapse and potential for rebound of biologic agents for psoriasis. Psoriasis Forum. 2010;16:36–42.CrossRef

40.

Wang X-Y, Zhang C-L, Wang W-H. Time to relapse after treatment withdrawal for different biologics used to treat plaque psoriasis. Chin Med J (Engl). 2020;133:2998–3000. https://doi.org/10.1097/CM9.0000000000001232.CrossRef

41.

Bellinato F, Girolomoni G, Gisondi P. Relapse of psoriasis in patients who asked to discontinue etanercept after achieving a stable clinical remission. Br J Dermatol. 2019;181:1319–20. https://doi.org/10.1111/bjd.18225.CrossRefPubMed

42.

Giunta A, Papoutsaki M, Bianchi L, Chimenti S. Efficacy and safety of infliximab in long-term treatment of plaque-type psoriasis: a comparative retrospective study on two different (continuous vs. relapse related) regimens P2765. J Am Acad Dermatol. 2007;56(2):AB190.

43.

Umezawa Y, Nobeyama Y, Hayashi M, Fukuchi O, Ito T, Saeki H, Nakagawa H. Drug survival rates in patients with psoriasis after treatment with biologics. J Dermatol. 2013;40:1008–13. https://doi.org/10.1111/1346-8138.12353.CrossRefPubMed

44.

Rivera R, Martorell A, López A, Salgado L, Sahuquillo A, de la Cueva P, Herranz P, Ratón JA, Ferrán M, Izu R, Ruiz-Genao D, García-Donoso C, Carrascosa JM. Maintenance of response following discontinuation of guselkumab and secukinumab in Spanish patients who participated in the ECLIPSE study. J Eur Acad Dermatol Venereol. 2021;35:e65–7. https://doi.org/10.1111/jdv.16809.CrossRefPubMed

45.

Chiu H-Y, Hui RC-Y, Tsai T-F, Chen Y-C, Chang Liao N-F, Chen P-H, Lai P-J, Wang T-S, Huang Y-H. Predictors of time to relapse following ustekinumab withdrawal in patients with psoriasis who had responded to therapy: an eight-year multicenter study. J Am Acad Dermatol. 2019. https://doi.org/10.1016/j.jaad.2019.01.035.CrossRefPubMed

46.

Down-titration and discontinuation strategies of tumour necrosis factor-blocking agents for rheumatoid arthritis in patients with low disease activity—PubMed, (n.d.). https://pubmed.ncbi.nlm.nih.gov/31125448/ (Accessed Feb 4, 2022).

Title: Time to Relapse After Discontinuing Systemic Treatment for Psoriasis: A Systematic Review
Authors: Marie Masson Regnault
Jason Shourick
Fatma Jendoubi
Marie Tauber
Carle Paul
Publication date: 30-04-2022
Publisher: Springer International Publishing
Keywords: Etanercept
Ustekinumab
Vulgar Psoriasis
Ixekizumab
Guselkumab
Published in: American Journal of Clinical Dermatology / Issue 4/2022
Print ISSN: 1175-0561
Electronic ISSN: 1179-1888
DOI: https://doi.org/10.1007/s40257-022-00679-y

At a glance: The STEP trials

Springer Medicine

Time to Relapse After Discontinuing Systemic Treatment for Psoriasis: A Systematic Review

Abstract

Background

Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 4/2022

The Evolving Landscape of Cutaneous Sarcoidosis: Pathogenic Insight, Clinical Challenges, and New Frontiers in Therapy

Chlormethine Gel Versus Chlormethine Ointment for Treatment of Patients with Mycosis Fungoides: A Post-Hoc Analysis of Clinical Trial Data

Evaluating the Longitudinal Course of Atopic Dermatitis: Implications for Clinical Practice

Clinical Effectiveness and Safety of Initial Combination Therapy with Corticosteroids and Rituximab in Bullous Pemphigoid: A Retrospective Cohort Study

Melanoma Brain Metastases: An Update on the Use of Immune Checkpoint Inhibitors and Molecularly Targeted Agents

JAK in the [Black] Box: A Dermatology Perspective on Systemic JAK Inhibitor Safety