Effective treatment of etanercept and phototherapy-resistant psoriasis using the excimer laser
1. University of California, San Francisco, Department of Dermatology, San Francisco, California
Treatment of moderate-to-severe plaque psoriasis often requires the use of phototherapy or systemic therapy, which includes immunosuppressants, retinoids, and biologic agents. Although biologic use is becoming increasingly popular, it is not uncommon for patients to experience treatment failure. We describe a patient who had a suboptimal response to etanercept monotherapy after twelve weeks of induction dosing (50 mg twice weekly), as well as to a combination of etanercept (50 mg once weekly-maintenance dosing) and narrowband ultraviolet B (NB-UVB) phototherapy three times weekly for an additional twelve weeks. Noticeable improvement was noted after the addition of NB-UVB and the patient’s promising response to phototherapy influenced further management. Etanercept and NB-UVB were discontinued and the patient was initiated on excimer laser treatments twice weekly. After 4 weeks, the patient had a 75 percent reduction in Psoriasis Area Severity Index (PASI) score and after 7 weeks had over 95 percent clearance of psoriasis. The unique properties of the excimer laser may account for its clinical efficacy in our patient as well as in other cases of recalcitrant psoriasis. We propose that the excimer laser be considered in cases of biologic or conventional phototherapy failure in addition to being a standard treatment option or adjunct for the treatment of psoriasis.
Psoriasis is a chronic, systemic inflammatory disease with a prevalence of 2-3 percent globally . Moderate-to-severe disease affects nearly a quarter of psoriasis patients and usually warrants phototherapy or systemic treatment for optimal management . These treatment options include ultraviolet B (UVB), photochemotherapy, oral immunosuppressants, systemic retinoids, and biologic agents.
The use of biologic therapy has been increasing since the first Tumor Necrosis Factor (TNF)-α antagonist, etanercept, was approved in the United States and the European Union for moderate-to-severe psoriasis in 2004 . However, it is well known that biologic agents do not necessarily result in complete remission of psoriasis. It can be worthwhile to revisit traditional psoriasis therapies when changing management. This includes phototherapy, in particular, the 308 nanometer (nm) excimer laser, which is recognized as an effective treatment option for a variety of dermatologic conditions. The excimer laser has the potential to become a standard treatment option for psoriasis, as monotherapy or as part of combination therapy. Here we illustrate a case of generalized plaque psoriasis with suboptimal response to both etanercept and narrowband ultraviolet B (NB-UVB) phototherapy that was successfully treated with the excimer laser.
A 31-year-old male presented to the psoriasis clinic with a 6-year history of generalized plaque psoriasis and a treatment history limited to the use of topical corticosteroids. The patient was obese, but otherwise healthy and on no medications. Psoriasis Area Severity Index, or PASI (range 0-no disease to 72-maximum disease), which determines the severity of psoriasis by evaluation of erythema, induration, desquamation, and body surface area (BSA) involvement, was used to assess the patient. The patient’s initial PASI was 14.1. Response to therapy was measured by decrease in PASI and reduction in BSA involvement from baseline.
Etanercept was initiated at the induction dose of 50 mg subcutaneously twice weekly. Minimal improvement was observed at week 4 and week 8 visits, and the patient had a mild flare of disease by week 12. Owing to the lack of clinical improvement as well as the standard reduction of etanercept to the maintenance dose of 50 mg subcutaneously weekly at 12 weeks, NB-UVB was initiated to augment therapy. The patient received phototherapy three times weekly. By week 16, he had fair improvement of disease, with a decrease in PASI to 9.1, a 35 percent reduction in disease severity (Figure 1). He maintained this degree of improvement until the end of his 6-month trial of etanercept and had no adverse events occur over the duration of therapy.
Etanercept and NB-UVB were discontinued, and the patient had a 3-week “washout” period during which no treatment was used. Because his disease had been refractory to an adequate trial of etanercept, but showed a partial, yet promising, response to conventional phototherapy, the patient began targeted phototherapy with the 308 nm xenon-chloride excimer laser (Photomedex® XTRAC Velocity, Carlsbad, CA). Treatments were initiated twice weekly (separated by at least 48 hours). The patient was dosed at 1 MED (minimal erythema dose) of 200 mJ and increased by 10-15 percent MED each session, contingent on clinical response and presence of side effects. Clobetasol spray and calcitriol ointment were also offered to the patient to use in alternating two-week intervals up to twice daily. The patient began at PASI 13.9 and by week 3, his score had decreased to PASI 7.7 (Figures 2A and 2B). After 4 weeks of excimer laser therapy, the patient had more than a 75 percent reduction in PASI (Figure 2D). The patient continued to improve with biweekly treatments, and at the week 7 assessment, the patient had over 95 percent clearance of psoriasis. The patient continued with excimer treatments twice weekly for an additional 3 weeks, at which point he achieved complete clearance after a total of 21 laser sessions. The patient’s final treatment dose was 1461 mJ, or 7.3 MED (Figure 2E). All treatments were discontinued at this point. Upon follow-up, the patient maintains this level of improvement without any treatment, which at the time of this report, is 36 weeks post-treatment.
Biologic failure is not uncommon and we propose that prior to simply switching to another biologic agent, other treatment options should be considered, in particular the excimer laser. Our patient had a suboptimal response to etanercept, which may have related to the development of resistance to therapy. It is speculated that resistance occurs because of the formation of antibodies to a biologic agent, which may then decrease the concentration of bioavailable drug . Recently, anti-nuclear antibody (ANA) and anti-double stranded (anti-DS) DNA antibodies were found in patients who experience a loss of response to therapy; both can be measured to predict this loss of response . The addition of NB-UVB therapy has been found to both increase the speed and degree of psoriasis clearance, particularly in individuals who respond slowly to etanercept . The patient’s response to NB-UVB was encouraging and indicative of disease amenable to the use of the excimer laser.
In our patient’s case, we initiated therapy at 1 MED (200 mJ), which took into account plaque induration and Fitzpatrick skin type. For subsequent treatments, doses were increased 10-15 percent based on clinical observation and patient tolerance. The patient achieved PASI 75 after 8 treatments, PASI 95 after 14 treatments, and had complete clearance after 21 treatments. The patient remains clear 36 weeks after treatment discontinuation.
This may be compared to the findings of a review of targeted UVB for psoriasis in which three studies utilized the 308 nm excimer laser (Photomedex® XTRAC, Carlsbad, CA) . Dosage administration protocols varied but utilized increments of MED or percentages thereof. Trehan and Taylor  began with 1 MED and increased doses at each treatment by 25-30 percent; patients had a mean of 11 treatments. All patients who completed the study (n=15) had over 95 percent improvement in PASI and mean remission time was 14 weeks. Fikrle and Pizinger  initiated dosing at 2 MED with increases of 1 MED every other treatment. Of the cohort, 72 percent of patients (n=26) had a Psoriasis Severity Index (PSI) score improvement of over 77 percent. Clearance was maintained for 52 weeks in 6 patients. Feldman et al  studied 3 MED initial dosing schedules in which all subsequent dosages were titrated by clinical response. The majority of patients had improvement in <10 treatments, with 72 percent reaching PASI 75 in 6.2 treatments. Patients who cleared did so in a median of 8.7 weeks.
These results suggest that the 308 nm excimer laser is an effective treatment option for psoriasis. The majority of patients had a clinical response regardless of starting MED dose, subsequent dosages, and number of treatments. Utilizing higher initial MED dosages and aggressive titration may decrease time to clearance, but remission times varied. In our patient, the concurrent usage of the 308 nm excimer laser with intermittent use of clobetasol spray and calcitriol ointment could have played a role in treatment response.
The excimer laser is both an efficacious and safe treatment option for psoriasis. In contrast to conventional UV sources, excimer laser treats only lesional skin with the option of using supraerythemogenic doses (multiple times above the MED) that spares nonaffected skin . At the same time, it reduces cumulative dose (six times less when compared to NB-UVB) and induces faster clearance [6, 7]. The excimer laser utilized for our patient is effective for generalized psoriasis involving over 10 percent BSA .
The excimer laser can be used for commonly treatment-resistant sites such as the scalp, palms, elbows, knees, and soles as well as difficult-to-access intertriginous areas. Our patient had particularly recalcitrant plaques of the lower extremities that were more responsive to the excimer laser than NB-UVB. The thick, tenacious scale of these types of plaques may counteract the effects of phototherapy by scattering light . An increase in stratum corneum can proportionally decrease light penetration, and for UVB to be effective, it must be absorbed by the epidermis . The targeted supraerythemogenic dosing with the excimer laser may have overcome the plaques’ optical deflection, accounting for our patient’s excellent response to therapy (Figure 2).
The induction of T cell apoptosis is greater with the excimer laser than with conventional UVB or NB-UVB . T cells eliminated by the particular 308 nm wavelength clear from both the involved and uninvolved epidermis and dermis and this wavelength is directly cytotoxic to the T cells in psoriatic lesions [13, 14]. There is a decrease in keratinocyte proliferation that may be facilitated by the upregulation of p53 and decrease in Bcl-2 expression [13, 14]. These processes are thought to be responsible for the observed clinical improvement and induction of remission in excimer laser-treated patients.
The combination of laser and topical corticosteroids, retinoids, or keratolytics increases treatment efficacy by helping to decrease the scale, thickness, and inflammation of stubborn plaques. Our patient’s judicious use of clobetasol spray may have enhanced his response to the excimer laser.
Individuals who respond to excimer laser therapy often see the greatest improvement in the first half of total treatment duration . The majority of patients have more than 75 percent clearance after 6-10 excimer treatments [9, 11, 14, 15]. This was consistent with what we observed in our patient. Furthermore, remission may be maintained for up to two years .
Side effects related to the excimer laser are well tolerated and generally involve phototoxicity, i.e., erythema, hyperpigmentation, blistering, and xerosis . The excimer laser has no systemic side effects and is a safer treatment option than the biologic agents, which have concerns of lymphoma and other internal cancers, tuberculosis, histoplasmosis, congestive heart failure, and demyelinating disorders, among others. However, the long-term risks of the excimer laser are yet unknown, but may be similar to those of UVB phototherapy, i.e., carcinogenic risk and photodamage. Further study of the long-term follow-up of excimer laser patients study is needed.
Our patient had psoriasis recalcitrant to both etanercept and conventional UVB phototherapy. Biologic failure is not uncommon; therefore, it is useful to review all possible treatment options prior to initiating any biologic agent or switching between them. The excimer laser is a relatively new treatment option that is a worthwhile consideration in any psoriasis patient, including those with generalized disease, those who qualify for biologic treatment, and those who have failed biologic agents. Even if a patient had a suboptimal response to phototherapy, the excimer laser may be useful because of its ability to provide targeted therapy in supraerythemogenic doses that in turn, enhance the mechanism of action of UVB. We propose that the excimer laser may be useful in resistant psoriasis and considered an option as first-line therapy or after treatment failure.
References1. Kurd SK, Gelfand JM. The prevalence of previously diagnosed and undiagnosed psoriasis in US adults: results from NHANES 2003-2004. J Am Acad Dermatol. 2009 Feb;60(2):218-24. [PubMed]
2. Heffernan MP. Combining traditional systemic and biologic therapies for psoriasis. Semin Cutan Med Surg. 2010 Mar;29(1):67-9. [PubMed]
3. Pink AE, Fonia A, Allen MH, Smith CH, Barker JN. Antinuclear antibodies associate with loss of response to antitumour necrosis factor-alpha therapy in psoriasis: a retrospective, observational study. Br J Dermatol. 2010 Apr;162(4):780-5. [PubMed]
4. Wolf P, Hofer A, Legat FJ, Bretterklieber A, Weger W, Salmhofer W, et al. Treatment with 311-nm ultraviolet B accelerates and improves the clearance of psoriatic lesions in patients treated with etanercept. Br J Dermatol. 2009 Jan;160(1):186-9. [PubMed]
5. Gattu S, Pang ML, Pugashetti R, Malick F, Hong J, Bowers E, et al. Pilot evaluation of supra-erythemogenic phototherapy with excimer laser in the treatment of patients with moderate to severe plaque psoriasis. J Dermatolog Treat. 2010 Jan;21(1):54-60. [PubMed]
6. Bonis B, Kemeny L, Dobozy A, Bor Z, Szabo G, Ignacz F. 308 nm UVB excimer laser for psoriasis. Lancet. 1997 Nov 22;350(9090):1522. [PubMed]
7. Asawanonda P, Anderson RR, Chang Y, Taylor CR. 308-nm excimer laser for the treatment of psoriasis: a dose-response study. Arch Dermatol. 2000 May;136(5):619-24. [PubMed]
8. Mudigonda T, Dabade TS, Feldman SR. A review of targeted ultraviolet B phototherapy for psoriasis. J Am Acad Dermatol. 2011 Oct 13. [PubMed]
9. Trehan M, Taylor CR. Medium-dose 308-nm excimer laser for the treatment of psoriasis. J Am Acad Dermatol. 2002 Nov;47(5):701-8. [PubMed]
10. Fikrle T, Pizinger K. [The use of the 308 nm excimer laser for the treatment of psoriasis]. J Dtsch Dermatol Ges. 2003 Jul;1(7):559-63. [PubMed]
11. Feldman SR, Mellen BG, Housman TS, Fitzpatrick RE, Geronemus RG, Friedman PM, et al. Efficacy of the 308-nm excimer laser for treatment of psoriasis: results of a multicenter study. J Am Acad Dermatol. 2002 Jun;46(6):900-6. [PubMed]
12. Ozawa M, Ferenczi K, Kikuchi T, Cardinale I, Austin LM, Coven TR, et al. 312-nanometer ultraviolet B light (narrow-band UVB) induces apoptosis of T cells within psoriatic lesions. J Exp Med. 1999 Feb 15;189(4):711-8. [PubMed]
13. Bianchi B, Campolmi P, Mavilia L, Danesi A, Rossi R, Cappugi P. Monochromatic excimer light (308 nm): an immunohistochemical study of cutaneous T cells and apoptosis-related molecules in psoriasis. J Eur Acad Dermatol Venereol. 2003 Jul;17(4):408-13. [PubMed]
14. Trott J, Gerber W, Hammes S, Ockenfels HM. The effectiveness of PUVA treatment in severe psoriasis is significantly increased by additional UV 308-nm excimer laser sessions. Eur J Dermatol. 2008 Jan-Feb;18(1):55-60. [PubMed]
15. Housman TS, Pearce DJ, Feldman SR. A maintenance protocol for psoriasis plaques cleared by the 308 nm excimer laser. J Dermatolog Treat. 2004 Apr;15(2):94-7. [PubMed]
16. Kemeny L, Bonis B, Dobozy A, Bor Z, Szabo G, Ignacz F. 308-nm excimer laser therapy for psoriasis. Arch Dermatol. 2001 Jan;137(1):95-6. [PubMed]
© 2012 Dermatology Online Journal