Traditional systemic therapies for PsO are often not able to meet desired treatment goals, and high-dose and/or long-term use is associated with toxicities that can result in end-organ damage.
Despite remarkable improvements in PsO treatment outcomes with biologic therapy, many patients still do not achieve the desired goals, have a prolonged time to response, or fail to maintain efficacy improvements over time.
Treatment cycles identified as combined therapy range from 9.9% (PSONET registry ) to 25.1% (BADBIR registry – the inclusion of patients on bridging therapy (21.4%) may partly explain this difference ).
Rather than increasing the dosage of monotherapies, which may be limited due to concerns of accumulating toxicity, combined therapy is often employed by many dermatologists to improve overall treatment response and minimize adverse effects associated with higher doses.
Most patients will not need this kind of approach however there are specific groups that can benefit (see Table 1).
In sub-optimal responders, who would require high doses of the systemic agent associated with tolerability or safety concerns, combined therapies can be considered.
The main reason identified in registries to use combined therapy was psoriatic arthritis (in up to 30% of patients) as they may benefit from a broader immunosuppressive effect.
European consensus guidelines recommend that combined therapy should be considered for individuals who are switching to a biologic agent and in whom it may be useful to taper previous systemic therapy before discontinuation to prevent a disease flare.
In patients with a well-controlled systemic agent who unexpectedly experience a rebound or a flare, rather than switching to another drug we may consider the use of combined therapy for a short period.
Combined therapy may also be helpful in the prevention or treatment of adverse events in certain patients (e.g., use of retinoids in a patient at high risk of non-melanoma skin cancer, or methotrexate (MTX)in under treatment with interferon to prevent antidrug-antibodies formation).
Combined therapy with retinoids, is an old, well-known combination that provide better results than each regimen alone.
Both cyclosporine and phototherapy are associated with an increased carcinogenic risk, so this combination has not been widely used or studied.
In a small study, patients underwent concomitant treatment with cyclosporin-A (CsA) and UVB. The therapeutic synergism of the two treatments allowed to initiate treatment with a CsA and a lower dosage phototherapy than used in a monotherapy scenario (2.5 mg/kg/day instead of 3.5-4 mg/kg/day, and UVB twice a week) .
Few studies found small statistically significant differences in favor of UV-B/psoralen plus ultraviolet A (PUVA) plusMTX[4-5].
Among the biologics, etanercept and MTX combination therapy is the most well studied, and this combination is more effective than either etanercept or MTX alone, but adverse events are high (74.9 % combination therapy vs. 59.8 % etanercept monotherapy) .
Infliximab: in the IMPACT2 study at week 54, PASI 75 MTX + infliximab was 53% vs. 48% infliximab only (no P value reported) and the incidence of infusion reactions was significantly lower in combination MTX + infliximab .
Adalimumab: a small study (n = 45) of combination therapy MTX + adalimumab vs. adalimumab dose escalation reported PASI 50 at 12 weeks of 9 % vs. 25% and at 24 weeks 18 % vs. 35%, respectively, suggesting that at least for some patients, adalimumab dose escalation may be more beneficial than adding MTX .
Iskandar IYK, Ashcroft DM, Warren RB, et al. Patterns of biologic therapy use in the management of psoriasis: cohort study from the British Association of Dermatologists Biologic Interventions Register (BADBIR). Br J Dermatol. 2017;176; 1297-307.
Mahajan R, KaurI, KanwarAJ. Methotrexate/narrowband UVB phototherapy combination vs. narrowband UVB phototherapy in the treatment of chronic plaque-type psoriasis: a randomized single-blinded placebo-controlled study. J Eur Acad Dermatol Venereol. 2010;24:595-600.
Asawanonda P, Nateetongrungsak Y. Methotrexate plus narrowband UVB phototherapy versus narrowband UVB phototherapy alone in the treatment of plaque-type psoriasis: a randomized, placebo-controlled study. J Am Acad Dermatol. 2006;54:1013-8.
Kircik L, Bagel J, Korman N, et al. Utilization of narrow-band ultraviolet light B therapy and etanercept for the treatment of psoriasis (UNITE): efficacy, safety, and patient-reported outcomes. J Drugs Dermatol. 2008;7:245-53.
De Simone C, D’Agostino M, Capizzi R, et al. Combined treatment with etanercept 50 mg once weekly and narrow-band ultraviolet B phototherapy in chronic plaque psoriasis. Eur J Dermatol. 2011;21:568-72.
Mrowietz U, Adamczyk A, Augustin M, et al. New information about fumaric acid esters (Fumaderm): results of a workshop of experts - German]. J Dtsch Dermatol Ges. 2011;9:1-13.
Tzaneva S, Geroldinger A, Trattner H, Tanew A. Fumaric acid esters in combination with a 6- week course of narrow-band UVB provides for an accelerated response as compared to fumaric acid esters monotherapy in patients with moderate to severe plaque psoriasis: A randomized prospective clinical study. Br J Dermatol. 2018;178:682-8.
Lynde CW, Gupta AK, Guenther L, et al. A randomized study comparing the combination of nbUVB and etanercept to etanercept monotherapy in patients with psoriasis who do not exhibit an excellent response after 12 weeks of etanercept. J Dermatolog Treat. 2012;23:261-7.
Park KK, Wu JJ, Koo J. A randomized, ‘head-to-head’ pilot study comparing the effects of etanercept monotherapy vs. etanercept and narrowband ultraviolet B (NB-UVB) phototherapy in obese psoriasis patients. J Eur Acad Dermatol Venereol. 2013;27(7):899-906.
Wolf P, Weger W, Legat FJ, et al. Treatment with 311-nm ultraviolet B enhanced response of psoriatic lesions in ustekinumab-treated patients: a randomized intraindividual trial. Br J Dermatol. 2012;166:147-53.
Gottlieb AB, Langley RG, Strober BE, et al. A randomized, double-blind, placebo-controlled study to evaluate the addition of methotrexate to etanercept in patients with moderate to severe plaque psoriasis. Br J Dermatol. 2012;167:649-57.
Kavanaugh A, Krueger GG, Beutler A, et al; IMPACT 2 Study Group. Infliximab maintains a high degree of clinical response in patients with active psoriatic arthritis through 1 year of treatment: results from the IMPACT 2 trial. Ann Rheum Dis. 2007;66:498-505.
Wee JS, Petrof G, Jackson K, et al. Infliximab for the treatment of psoriasis in the U.K.: 9 years’ experience of infusion reactions at a single centre. Br J Dermatol. 2012;167: 411-6.
Gisondi P, Del Giglio M, Cotena C, Girolomoni G. Combining etanercept and acitretin in the therapy of chronic plaque psoriasis: a 24-week, randomized, controlled, investigator-blinded pilot trial. Br J Dermatol. 2008;158:1345-9.
Smith EC, Riddle C, Menter MA, Lebwohl M. Combining systemic retinoids with biologic agents for moderate to severe psoriasis. Int J Dermatol. 2008;47:514-8.
With this collection of summaries from selected presentations at SPIN 2019, and interviews with international experts, we hope to share with you some of the highlights of this year’s congress. The international network met … [ Read all ]