PUVA: Shall we still use it for psoriasis in 2019? Ben Stoff MD, MA Associate Professor Emory Department of Dermatology Phototherapy: F003 March 1, 2019
DISCLOSURE OF RELEVANT RELATIONSHIPS WITH INDUSTRY Ben Stoff MD MA Phototherapy: F003 PUVA: Shall we still use it for psoriasis in 2019? Relevant financial relationships: None
Objectives Clarify the question Framework for judging treatment as obsolete Benefits of PUVA for psoriasis Potential harms of PUVA for psoriasis Role of PUVA for psoriasis now and in the future
Psoriasis Clinical Practice Guidelines from the past Oral PUVA is indicated and recommended for adults with generalized psoriasis Strength of recommendation = A Menter A, Korman NJ, Elmets CA, Feldman SR, Gelfand JM, Gordon KB, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 5. Guidelines of care for the treatment of psoriasis with phototherapy and photochemotherapy. J Am Acad Dermatol. 2010 Jan;62(1):114-35.
Shall we still use PUVA for psoriasis in 2019? What are we really asking? Shall we recommend PUVA for psoriasis? Shall we offer PUVA for psoriasis? Active paternalism telling patients what to do in order to benefit them Passive paternalism restricting patient choice to avoid harming them What question are we not asking? Shall we still use phototherapy for psoriasis in 2019? Beauchamp TL, Childress JF. Principles of Biomedical Ethics, 6 th ed. Oxford University Press. 2009.
Framework: When should a clinical practice guideline be abandoned? Changes in existing benefits and harms of the intervention Changes in outcomes considered important Changes in available alternative interventions Change in evidence that current practice is optimal Changes in values placed on outcomes Changes in available resources Judgment of an expert (Dr. Lim) and a generalist (me) Institute of Medicine 2011. Clinical Practice Guidelines We Can Trust. Washington, DC: The National Academies Press. https://doi.org/10.17226/13058. Shekelle P, Eccles MP, Grimshaw JM, Woolf SH. When should clinical guidelines be updated? BMJ. 2001 323(7305): 155-157.
Objectives Clarify the question Framework for judging treatment as obsolete Benefits of PUVA for psoriasis Potential harms of PUVA for psoriasis Role of PUVA for psoriasis now and in the future
Benefits of PUVA for Psoriasis: Compared to NBUVB, PUVA leads to: Greater reduction in BSA Faster reduction in BSA More durable remission Disclaimer about phototherapy data for psoriasis: Heterogeneous studies (e.g. methods, end points, dosing, duration) Chen X, Yang M, Cheng Y, Liu GJ, Zhang M. Narrow-band ultraviolet B phototherapy versus broad-band ultraviolet B or psoralen-ultraviolet A photochemotherapy for psoriasis. The Cochrane database of systematic reviews. 2013.
Greater Reduction in BSA Oral PUVA PASI-75 = 73% Clearance = 79% NBUVB PASI-75 = 62% Clearance = 68% Clearance rate = 80% OR 2.79 (95% CI: 1.40-5.55) Clearance rate = 70% Almutawa F, Alnomair N, Wang Y, Hamzavi I, Lim HW. Systematic review of UV-based therapy for psoriasis. Amer J Clin Dermatol. 2013;14(2):87-109. Archier E, Devaux S, Castela E, et al. Efficacy of psoralen UV-A therapy vs. narrowband UV-B therapy in chronic plaque psoriasis: a systematic literature review. JEADV. 2012;26 Suppl 3:11-21.
Faster and More Durable Reduction in BSA Oral PUVA Time/treatments to PASI-75: 49.2 days (12.7 treatments) NBUVB Time/treatments to PASI-75: 65.6 days (16.4 treatments) Treatments to clearance: 17 Treatments to clearance: 25 Remission at 6 months OR = 2.73 (95% CI 1.19-6.27) Dayal S, Mayanka, Jain VK. Comparative evaluation of NBUVB phototherapy and PUVA photochemotherapy in chronic plaque psoriasis. Ind J Dermatol Venerol. 2010;76(5):533-537. Archier E, Devaux S, Castela E, et al. Efficacy of psoralen UV-A therapy vs. narrowband UV-B therapy in chronic plaque psoriasis: a systematic literature review. JEADV. 2012;26 Suppl 3:11-21.
Objectives Clarify the question Framework for judging treatment as obsolete Benefits of PUVA for psoriasis Potential harms of PUVA for psoriasis Role of PUVA for psoriasis now and in the future
Potential Harms of PUVA Health-related: Short-term Long-term Financial/logistical: Cost/availability of psoralens
Health-related Potential Harms of PUVA: Short-term Oral PUVA Erythema and blistering 17% 70% grade II Withdrawal from trial = 5% NBUVB Erythema and blistering 7.8% 40% grade II Withdrawal from trial = 2% Nausea Significantly greater incidence Almutawa F, Alnomair N, Wang Y, Hamzavi I, Lim HW. Systematic review of UV-based therapy for psoriasis. Amer J Clin Dermatol. 2013;14(2):87-109. Dayal S, Mayanka, Jain VK. Comparative evaluation of NBUVB phototherapy and PUVA photochemotherapy in chronic plaque psoriasis. Ind JDermatol Venerol. 2010;76(5):533-537. Chen X, Yang M, Cheng Y, Liu GJ, Zhang M. Narrow-band ultraviolet B phototherapy versus broad-band ultraviolet B or psoralen-ultraviolet A photochemotherapy for psoriasis. The Cochrane database of systematic reviews. 2013.
Health-related Potential Harms of PUVA: Long-term Oral PUVA Skin cancer SCC: 25x (~tx # > 300 vs < 100), penile, post-d/c BCC: 11.7x (> 300 tx) MCC 3 cases (100x general pop) Melanoma US studies: increased risk (2.3x), > 250 tx (4.1x), time >15 y vs < 15 y (5x) European studies: no increased risk No increased risk in Asians, ME, Africans Pigmentation lentigines Cataracts no increased incidence NBUVB No increased risk of skin cancer No increased incidence Stern RS, Study PF-U. The risk of squamous cell and basal cell cancer associated with psoralen and ultraviolet A therapy: a 30-year prospective study. J Amer Acad Dermatol. 2012;66(4):553-562. Archier E, Devaux S, Castela E, et al. Carcinogenic risks of psoralen UV-A therapy and narrowband UV-B therapy in chronic plaque psoriasis: a systematic literature review. JEADV. 2012;26 Suppl 3:22-31. Murase JE, Lee EE, Koo J. Effect of ethnicity on the risk of developing nonmelanoma skin cancer following long-term PUVA therapy. International journal of dermatology. 2005;44(12):1016-1021. Archier E, Devaux S, Catela E et al. Ocular damage in patients with psoriasis treated by psoralen UV-A therapy or narrowback UVB: A systematic literature review. JEADV 2012; 26 Suppl 3:32-5.
Financial/Logistical Harms of PUVA: Cost of psoralens Retail price for 1 month supply (50-70kg person) of oral psoralen (generic) = ~$1000 Retail price for 1 month supply of oral psoralen (generic) = ~$3500 Goodrx.com
Objectives Clarify the question Framework for judging treatment as obsolete Benefits of PUVA for psoriasis Potential harms of PUVA for psoriasis Role of PUVA for psoriasis now and in the future
Framework: When should a clinical practice guideline be abandoned? Benefits and harms of the intervention Skin cancer Outcomes considered important NPF treat to target Available alternative interventions Biologics Evidence that current practice is optimal Comorbidities Available resources Cost and availability of PUVA Institute of Medicine 2011. Clinical Practice Guidelines We Can Trust. Washington, DC: The National Academies Press. https://doi.org/10.17226/13058. Shekelle P, Eccles MP, Grimshaw JM, Woolf SH. When should clinical guidelines be updated? BMJ. 2001 323(7305): 155-157.
Role of PUVA for Psoriasis: In patients for whom phototherapy is appropriate Consider recommending for: Short-term use (< 100-150 treatments) Darker skin types (FP > III) Avoiding systemic immunomodulation Means to afford psoralen and access to UVA unit Consider offering for: If available and not contraindicated
Psoriasis Clinical Practice Guidelines in press PUVA still recommended for treatment of generalized psoriasis in adults Strength of recommendation = A Short-term PUVA monotherapy is more efficacious than NBUVB for treatment of generalized psoriasis in adults Strength of recommendation = B AAD, 2019, In press
bstoff@emory.edu Questions???