Local radiation and phototherapy are the most cost-effective treatments for stage IA mycosis fungoides: A comparative decision analysis model in the United States.

BACKGROUND: Treatments for early-stage mycosis fungoides (MF) include topical steroids, topical nitrogen mustard, topical bexarotene, narrowband ultraviolet B (NBUVB), psoralen plus ultraviolet A (PUVA), and local radiation. The relative cost-effectiveness of each treatment given the differences in treatment failure, disease progression, and therapy escalation is not established. OBJECTIVE: To compare the cost-effectiveness (CE) of treatment options for stage IA MF. METHODS: A state-transition model was constructed with health states of stage IA to stage IV disease, no MF, and death. Treatment-specific remission and relapse rates were obtained from the literature. Lifetime costs were calculated by accounting for medications, office visits, laboratory monitoring, related procedures, work absences, and travel. RESULTS: The order of CE of the study treatments was determined to be as follows: local radiation, $225,399 for 15.40 life-years (LYs); NBUVB, $344,728 for 15.17 LYs; PUVA, $371,741 for 15.07 LYs; topical corticosteroids, $469,354 for 14.65 LYs; topical nitrogen mustard, $951,662 for 14.29 LYs; and topical bexarotene, 11,892,496 for 13.55 LYs. Sensitivity analyses confirmed the CE rankings. LIMITATIONS: We assumed a constant probability of response, relapse rates, and 3-month treatment intervals. CONCLUSIONS: Local radiation is the most cost-effective treatment for limited local disease, whereas phototherapy (NBUVB or PUVA) is cost-effective for generalized disease. Our findings can serve to inform future studies and recommendations regarding selection of therapy for stage IA MF.

The risk of squamous cell and basal cell cancer associated with psoralen and ultraviolet A therapy: a 30-year prospective study.

BACKGROUND: By 1977, psoralen and ultraviolet A (PUVA) was established as a highly effective therapy for psoriasis. Because of concerns about potential long-term adverse effects, particularly cancer, the PUVA Follow-Up Study was established to assess long-term risk and benefits of PUVA. OBJECTIVE: We sought to determine the association of certain squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) risk with exposure to PUVA. METHODS: For nearly 30 years, this prospective cohort study of 1380 patients with psoriasis first treated with PUVA in 1975 to 1976 documented exposures and incident events including biopsy-proven skin cancers. RESULTS: From 1975 to 2005, 351 of 1380 (25%) cohort patients developed 2973 biopsy-proven SCC and 330 (24%) developed 1729 BCCs. After adjusting for age, gender, and significant confounders, the risk of developing one or more SCC in a year was strongly associated with total number of PUVA treatments (350-450 vs <50 treatments, incidence rate ratio [IRR] = 6.01, 95% confidence interval [CI] = 4.41-8.20). When all tumors are included this risk is significantly higher (IRR = 20.92, 95% CI = 14.08-31.08). Corresponding risks for BCC were much lower (person counts IRR = 3.09, 95% CI = 2.36-4.06; tumor counts IRR = 2.12, 95% CI = 1.47-3.05). LIMITATIONS: This was an observational prospective study of a cohort with severe psoriasis. An unknown factor associated with higher dose exposure to PUVA in our cohort that was not included in our analysis could account for the observed associations. CONCLUSION: Exposure to more than 350 PUVA treatments greatly increases the risk of SCC. Exposure to fewer than 150 PUVA treatments has, at most, modest effects on SCC risk. Even high-dose exposure to PUVA does not greatly increase BCC risk. The risks of SCC in long-term PUVA-treated patients should be considered in determining the risk of this therapy relative to other treatments for severe psoriasis.

Very severe psoriasis is associated with increased noncardiovascular mortality but not with increased cardiovascular risk.

It has been hypothesized that severe psoriasis is an independent risk factor for cardiovascular disease (CVD). We prospectively studied patients with severe psoriasis treated with psoralens and ultraviolet-A therapy (PUVA) who enrolled in a cohort study in 1975-1976. From 1977 to 2005, 617 of the 1,376 patients (45%) died. Compared with the general population, cohort death rates were significantly higher than expected (standard mortality ratio (SMR) = 1.1, 95% confidence interval (CI) = 1.02-1.20). The number of deaths due to CVD (SMR = 1.02, 95% CI = 0.9-1.6) was nearly identical to the expected number. Deaths due to liver disease were significantly elevated (SMR = 4.04, 95% CI = 2.76-5.70). Patients with exceptionally severe psoriasis at entry (>42% body surface area (BSA)) had a significantly increased risk of death compared with less severely affected cohort members (all-cause hazard ratio (HR) = 1.42, 95% CI = 1.18-1.69) as well as for deaths because of causes other than cancer or CVD (multivariate HR 1.56, 95% CI = 1.14-2.13). Only patients with exceptionally severe psoriasis had an increased mortality risk compared with both the general population and other cohort members with less extensive but still severe psoriasis. These increases were not significant for CVD. Our data do not support the hypothesis that severe psoriasis is an independent risk factor for CVD. However, exceptionally severe psoriasis is associated with increased all-cause mortality.

Clinical severity of psoriasis in last 20 years of PUVA study.

OBJECTIVE: To assess the severity of psoriasis over time. DESIGN: We analyzed the results of structured dermatologic examinations administered over a 20-year period beginning 10 years after study enrollment. SETTING: The PUVA [psoralen-UV-A] Follow-up Study, which is a prospective cohort study. PATIENTS: The analyses were restricted to 815 patients (83.2% of those eligible) who underwent at least 2 of 4 possible examinations between 1985 and 2005. MAIN OUTCOME MEASURE: A 4-point physician global assessment (PGA). RESULTS: The distribution of the PGA levels in the study group did not change significantly over time, except that in 2005 more patients had no psoriasis compared with patients who underwent examinations in the previous study years (9.6% vs < 5.1%, P < .03). The PGA level changed more than 1 level between examinations in only 14% of patients. Multistate Markov models estimated that patients had a likelihood of about 80% to remain at the same PGA level 1 year later. After 10 years, this likelihood varied between 19% and 53%, depending on the PGA level. Except for patients who were clear of disease at baseline, on average patients had about 1 year without psoriasis over 20 years. On average, individuals with moderate to severe disease remained at these levels for 11 or more years. Conclusion Three decades after a large and diverse group of patients sought a cure for their psoriasis, consistent control of their psoriasis often had not been achieved.

Use of biological agents in patients with moderate to severe psoriasis: a cohort-based perspective.

OBJECTIVE: To compare characteristics of patients enrolled in a long-term multicenter cohort trial who had used biological therapies for treatment of psoriasis with those who had not used these agents. DESIGN: Retrospective analysis of users vs nonusers of biological therapies. SETTING: Database from the PUVA Follow-up Study, a multicenter, 30-year study of patients originally treated with psoralen UV-A (PUVA) for moderate to severe psoriasis. Patients A total of 521 patients who completed the last cycle of follow-up of the PUVA Follow-up Study. MAIN OUTCOME MEASURES: Demographic data, severity data (physician global assessment), type of biological therapy used, patients' opinions about their therapy, and their best treatment. RESULTS: Seventy-four of 521 patients (14%) used biological therapies: 65% etanercept (n = 48), 22% infliximab (n = 16), 11% efalizumab (n = 8), and 8% alefacept (n = 6). Users of biological therapies were younger, had more formal education, and were more likely to have had a greater extent of psoriasis at entry than the other cohort members. In 1998, those who used biological treatments were more likely than other cohort members to have been assessed as having severe psoriasis. In 2004, no significant difference was noted. Users of etanercept considered this agent to be as effective as methotrexate and more effective in clearing their skin and having fewer adverse effects than PUVA or UV-B. The proportion of patients originally enrolled in the 16 centers who had used biological agents varied greatly (0%-33%). CONCLUSION: After short durations of therapy, patients' opinions about biological agents tended to be positive.

Psoralen plus ultraviolet A does not increase the risk of cataracts: a 25-year prospective study.

BACKGROUND: In some animal species, exposure of the unprotected eye to psoralen plus ultraviolet A (PUVA) therapy induces lens opacities. The relevance of these animal findings to human beings is not established. However, some case reports suggest that PUVA in human beings may increase the risk of lens abnormalities. OBJECTIVE: Our aim was to evaluate any possible associations between exposure to PUVA and increased risk of ocular lens abnormalities. METHODS: Since 1977 the PUVA follow-up study has periodically monitored the ocular status of 1237 cohort members with psoriasis using structured eye examinations. In our previous report we presented data results of the first 10 years of prospective study. This report includes data from two additional cycles of eye examinations that span an additional 14 years of follow-up. RESULTS: Based on our data from the last pre-1993 to final eye examination (2004), compared with that observed for the earlier period (first ever to last pre-1993 eye examination), the age-adjusted incidence of cataract did not increase significantly (incidence rate ratio = 1.04, 95% confidence interval = 0.82-1.31). In both the univariate and multivariate analyses increasing exposure to PUVA was not associated with a higher risk of cataract. LIMITATIONS: Our cohort principally enrolled middle-aged or older patients so our data do not permit us to assess the effects of PUVA on the eyes of younger persons. CONCLUSIONS: Increasing exposure to PUVA does not increase cataract risk among persons using eye protection at the rates used in our cohort.

Lymphoma risk in psoriasis: results of the PUVA follow-up study.

OBJECTIVE: To assess the risk of lymphoma in patients with psoriasis. DESIGN: Prospective cohort study that spans 30 years and a systematic review of the literature. SETTING: Sixteen university medical centers. PATIENTS: A total of 1380 patients with psoriasis who were initially treated with psoralen-UV-A (PUVA) from 1975 through 1976 and who underwent periodic interviews and physician examinations irrespective of their use of any treatment. MAIN OUTCOME MEASURE: Incidence of lymphoma relative to that expected in the general US population (original primary end point of the study). RESULTS: The incidence of lymphoma in patients who received PUVA and were not exposed to high levels of methotrexate was comparable to that expected in the general population (incidence rate ratio, 0.85; 95% confidence interval, 0.37-1.67) but was elevated among those exposed to high levels of methotrexate (> or =36 months) (incidence rate ratio, 4.39; 95% confidence interval, 1.59-12.06). CONCLUSION: Unless exposed to high levels of methotrexate, the risk of lymphoma among members of the PUVA Follow-up Study was comparable to that observed in the general population.

Traditional systemic treatments have not fully met the needs of psoriasis patients: results from a national survey.

BACKGROUND: Many psoriasis patients are dissatisfied with current therapies. However, patient-centered levels of satisfaction with individual treatments have not been well described. OBJECTIVE: To assess patients' satisfaction with 4 systemic treatment options available before 2002. METHODS: We used data from a recent national survey. Psoriasis patients were randomly recruited from the general US population, members of the Psoriasis Foundation, and persons who contacted the Psoriasis Foundation but did not join. The interview included questions about use and satisfaction with specific Psoriasis therapy. RESULTS: Of 1197 psoriasis patients interviewed, 311 (26%) indicated current or past use of methotrexate, psoralen plus ultaviolet A (PUVA), cyclosporin, and/or acitretin (users). Compared with those who had never used any of these systemic therapies, users reported more extensive disease (adjusted odds ratio [OR] = 2.90, 95% confidence interval [CI] = 1.87-4.49) and higher Psoriasis Disability Index scores (category V: adjusted OR = 2.31, 95% CI = 1.22-4.36). After adjusting for these variables, more than one third of patients were dissatisfied with each therapy, except for PUVA (14%). Patients were most satisfied with methotrexate and PUVA. However, less than 40% of the users indicated they were very satisfied with any of the 4 therapies assessed. Only 10% of persons who ever used cyclosporin were currently using it. In a paired analysis, cyclosporin users were significantly less satisfied with cyclosporin than with other therapies ( P = .01). CONCLUSION: For most patients, none of the 4 systemic therapies widely utilized in 2002 for psoriasis were highly satisfactory. If we are to learn whether new treatments satisfy patients' needs, long term, prospective, comparative studies of heterogeneous patient populations that include patients' assessments are needed.

Inpatient hospital care for psoriasis: a vanishing practice in the United States.

BACKGROUND: Inpatient hospital care was a traditional approach to treat severe psoriasis. Since 1980, only modest innovations in psoriasis therapy have been introduced, but regulation and financing of inpatient hospital care have changed greatly. OBJECTIVE: We documented changes in the use of inpatient care in acute care hospitals for psoriasis in a cohort of individuals with severe psoriasis and nationally. METHODS: Using interviews, we quantified hospitalizations for psoriasis and other reasons among the PUVA Follow-up Study cohort. We used National Hospital Discharge Survey data to determine national trends in hospitalization rates. RESULTS: In 2 decades, national rates of hospitalization primarily for psoriasis decreased more than 80%. Among our cohort of persons with severe psoriasis, the age-adjusted rate of hospital days for psoriasis decreased more than 60% during this period. CONCLUSION: Currently, hospitalization in acute care hospitals is seldom used to care for persons with psoriasis.

Oral retinoid use reduces cutaneous squamous cell carcinoma risk in patients with psoriasis treated with psoralen-UVA: a nested cohort study.

BACKGROUND: Small open studies of patients at high risk for squamous cell carcinoma (SCC) of the skin suggest that oral retinoid use reduces the risk of these tumors. Among patients at lower risk, randomized trials of low doses of retinoids did not demonstrate significant chemopreventive effects. Patients with psoriasis treated with oral psoralen-UVA have a high risk of SCC development. Oral retinoids are used to treat psoriasis. We performed a nested cohort study to assess whether oral retinoids reduce skin cancer risk among patients with psoriasis exposed to psoralen-UVA. METHODS: From 1985 to 2000, 135 patients (11.3% of surviving patients in our cohort) used retinoids for at least 26 weeks in 1 year or more. For these 135 patients, we compared each person's SCC and basal cell carcinoma incidence during years of substantial oral retinoid use and other years. We used Poisson regression models to adjust for potential confounders. RESULTS: In a paired analysis, which compared each patient's own tumor experience while using and not using retinoids, retinoid use was associated with a 30% reduction in SCC incidence (196 SCCs/1000 and 302 SCCs/1000 years of use and no use, respectively; P =.002). After adjusting for other factors associated with SCC risk, the incidence of SCC was significantly decreased during years of substantial retinoid use (incidence rate ratio = 0.79; 95% confidence interval = 0.65, 0.95). Oral retinoid use and basal cell carcinoma incidence were not significantly associated. CONCLUSION: In patients with psoriasis treated with psoralen-UVA, systemic retinoid use reduced SCC risk but did not significantly alter basal cell carcinoma incidence.

The increased risk of skin cancer is persistent after discontinuation of psoralen+ultraviolet A: a cohort study.

Psoralen+ultraviolet A-treated psoriasis patients are at increased risk for nonmelanoma skin cancer. To assess the persistence of cancer risk among patients who have discontinued psoralen+ultraviolet A and the risk of a first tumor with the passage of time, we prospectively studied the incidence in a cohort of 1,380 psoriasis patients treated with psoralen+ultraviolet A. We observed a total of 27,840 person-years of which 59.4% were considered years without psoralen+ultraviolet. No significant decrease in risk was noted during the first 15 years after psoralen+ultraviolet A was discontinued. Subsequently, the risk of squamous cell carcinoma was reduced (incidence rate ratio=0.79; 95%CI=0.62, 1.01 on treatment vs >15 years off). After 25 years, about 7% of patients with < or =200 psoralen+ultraviolet A treatments and more than half of the patients with > or =400 treatments develop at least one squamous cell carcinoma. After 25 years, almost one third of the patients exposed to > or =200 treatments developed at least one basal cell carcinoma. In conclusion, substantial exposure to psoralen+ultraviolet A dramatically increases the risk of nonmelanoma skin cancer and prior exposure to psoralen+ultraviolet A remains an important issue in the management of patients because the cancer risk associated with psoralen+ultraviolet A is persistent.

Actinic degeneration and pigmentary change in association with psoralen and UVA treatment: a 20-year prospective study.

BACKGROUND: Changes in the appearance of the skin including actinic degeneration and pigmentary changes have been noted in patients treated with psoralen and UVA (PUVA). OBJECTIVE: Our purpose was to quantify risk factors for increased extent and progression of actinic degeneration and pigmentary changes in the skin of patients treated with PUVA. METHODS: On the basis of standardized dermatologic examination conducted in 1977 and 1998 of patients enrolled in the PUVA Follow Up Study, we assessed the prevalence of and changes in the extent of actinic degeneration and pigmentary abnormalities on the hands and buttocks. RESULTS: From 1977 to 1998, the prevalence of moderate or severe actinic degeneration increased from 15.6% to 60.5% on the hands and from 2.2% to 21.3% on the buttocks. During this same period, the prevalence of pigmentary changes of this degree increased from 15.6% to 58.6% on the hands and 12.6% to 24.7% on the buttocks. Extent of exposure to PUVA was the strongest predictor of an increased extent of clinical actinic degeneration or pigmentary change. CONCLUSION: Long-term exposure to PUVA is associated with persistent increases in actinic degeneration and pigmentary abnormalities of the skin on both usually sun-exposed and sun-protected sites.

p53 mutation in nonmelanoma skin cancers occurring in psoralen ultraviolet a-treated patients: evidence for heterogeneity and field cancerization.

A combination of psoralens and ultraviolet A radiation is widely used to treat psoriasis. Long-term, high-dose exposure to psoralen + ultraviolet A is associated with an increased risk of nonmelanoma skin cancer, particularly squamous cell carcinoma. In this study, we used p53 mutations as a molecular marker to determine the separate contributions of psoralen + ultraviolet A and other ultraviolet exposures, such as ultraviolet B for skin cancer development in psoralen + ultraviolet A-treated psoriasis patients. The results indicated that of 69 tumors analyzed, 37 (54%) tumors had one or more p53 mutations. Of 37 tumors with mutations, 17 (46%) tumors had only ultraviolet-type mutations, two (5%) tumors had only psoralen + ultraviolet A-type mutations, and 18 (49%) tumors had both types of mutations. Interestingly, psoralen + ultraviolet A-type p53 mutations were more frequent than ultraviolet type in tumors arising in patients with high-dose exposure to psoralen + ultraviolet A. Field cancerization and tumor heterogeneity appeared to occur frequently in the same patient and even in the same tumor. This study's data suggest that psoralen + ultraviolet A-induced p53 mutations may play an important part in the development of nonmelanoma skin cancer in psoralen + ultraviolet A-treated patients, but these mutations are likely to act in concert with the effects of other carcinogenic exposures, particularly ultraviolet B, in the development of skin cancer.