Efficacy, safety, and cost of Goeckerman therapy compared with biologics in the treatment of moderate to severe psoriasis

Psoriasis is a chronic inflammatory dermatosis that affects about 0.6–4.8% of the general population.1,2 It has a substantial impact on the quality of life, comparable with that of other major medical illnesses, such as cancer, diabetes, and heart disease.3 The original Goeckerman therapy described by Dr Goeckerman in 1925 has undergone modifications over the years without compromising the safety profile.4,5 The classic regimen currently used at our institution includes dermal application of 2% crude coal tar three times daily and exposure to incremental doses of broad-band ultraviolet B (UVB) radiation, 7 days a week, as described previously.6,7 There are a broad range of other treatments available from topical therapies to oral immunomodulating agents, such as retinoids, methotrexate, and cyclosporin.1,8,9 Most agents can be used alone or in combination.8 The goal of all treatments is to induce and maintain remission with minimal side-effects from therapy. The introduction of new monoclonal antibodies directed towards a variety of inflammatory cytokines, including tumor necrosis factor-α (TNF-α) inhibitors, referred to generally as biologic agents,10 has further revolutionized our treatment of this chronic disease. These agents have been developed from an understanding of the molecular basis of the disease by targeting specific molecules in the inflammatory process.11 Although they target a specific molecule in the inflammatory process, the targeted molecule itself is not specific for psoriasis as a disease. Unfortunately, there is still no magic cure for psoriasis or even for long-term remission. The approval for the use of a drug in the treatment of psoriasis is based on efficacy using the Psoriasis Area and Severity Index (PASI), and not on head-to-head comparisons with well-known safe and efficacious treatments. Little attention is given to the duration of remission in these clinical trials. Efficacy in a chronic disease such as psoriasis, should not be based solely on the induction of remission, but should also depend on the ability of any course of treatment to maintain that remission. When considering therapy for any chronic disease, three criteria need to be addressed by the treating physician, namely safety, efficacy, and cost. The aim of this study is to compare the efficacy of Goeckerman treatment, using the duration of remission as the main criterion, with published reports on the duration of remission of biologic agents. As a secondary objective, the safety and annual cost of Goeckerman therapy are compared with the data reported for biologics. All patients who underwent Goeckerman treatment were identified from an existing database over a 25-month period from May 2005 to May 2007. The study was approved by the Mayo Clinic Institutional Review Board. The history was reviewed retrospectively and data were extracted with regard to the number and type of previous treatments, age and sex of the patients, and whether or not they had home UVB. The duration of remission, defined as the duration of response off treatment, was obtained from the history if the patient had received previous Goeckerman treatment(s), or by a phone call after completion of Goeckerman therapy. This was calculated in months from the time of discharge to the time of re-flare of psoriasis to the moderate to severe level [> 10% body surface area (BSA)]. If the patient was started on another course of Goeckerman therapy or any systemic treatment for psoriasis, that time was considered to be the end of remission. Fifty-one patients were selected who fitted the criteria for inclusion. All patients had moderate to severe psoriasis (> 10% BSA) according to the criteria for admission to the Goeckerman treatment program. All patients underwent 3 weeks of Goeckerman treatment with 2% crude coal tar and daily broad-band UVB, given in a general “8” with a Hanovia lamp, as described previously in detail.7 According to the criteria for the endpoint of discharge from Goeckerman therapy, all patients needed to show a 100% response (clear), with no evidence of scale, plaque elevation, or erythema. Patients with a few residual resistant erythematous or mildly elevated plaques were counted as “almost clear” and designated as > 90% BSA improvement in their global scale at discharge. Patients were not on any other antipsoriasis medications, except topical steroids or emollients, prior to, during, or after the initiation of Goeckerman treatment. If the patients continued on outpatient UVB as a maintenance program, this was noted in the results. A follow-up questionnaire and/or phone call was performed if the information was not available in the history. A review of electronic databases up to January 2008 was performed to determine the duration of remission of various biologics from the literature.12–30 Fifty-one patients (34 females and 17 males) were included in the study, selected on the basis of the criteria stated in the “Methods.” The age range was 9–86 years. Table 1 shows that the average duration of remission was 9.5 months for all 51 patients. The median was 12 months and the range was 1–24 months. As shown in Table 2, the patients were divided into five groups according to the treatments received in addition to Goeckerman therapy. Group 1 included patients with no previous systemic treatment, group 2 included patients who underwent Goeckerman therapy after failing systemic treatment, group 3 included patients who did not continue home UVB after discharge from Goeckerman therapy, group 4 included patients who continued with home UVB after discharge from Goeckerman therapy, and group 5 included patients who received no previous systemic treatments and continued home UVB after discharge. The mean and median durations of remission were highest in groups 4 and 5 at 12.4 and 11.7 months for the mean and 12 months for the median, respectively. The lowest duration for remission was in group 2, in patients who had failed previous systemic treatments. The duration of remission in this group was 6 months for the median and 8 months for the mean. There was no statistically significant difference between comparable groups. Psoriasis is a chronic skin disorder that has a tremendous impact on the lives of patients, affecting them physically, psychologically, and socially, and often requires long-term systemic treatments. The three major criteria to be considered by the treating physician for a chronic disease like psoriasis are safety, efficacy, and cost. Two measures are used to assess the efficacy of therapeutic agents in psoriasis, namely the induction of remission, as assessed by the PASI score, and the duration of this remission until re-flare, which is the goal of this study. The approval of new agents generally relies on acute efficacy as measured by the PASI score;12–30 in general, a decrease in severity of 75% (PASI 75) is the standard measure. The efficacy of Goeckerman therapy in inducing remission, as measured by the decrease in PASI, in comparison with other psoriasis treatments is well documented in the literature. Leon et al.2 recently reviewed the efficacy and safety of the most scientifically acceptable clinical trials published for psoriasis therapy from 1986 to 2006. The percentage PASI 75 reduction at week 12 obtained by Goeckerman therapy and retinoid plus psoralen plus UVA (Re-PUVA) was 100%, compared with 49% and 34% for etanercept 50 mg twice weekly and 25 mg twice weekly, respectively, 31.4% for efalizumab, and 21% for alefacept. The authors concluded that the risk–benefit was more favorable for Goeckerman therapy and Re-PUVA. In another study, Lee and Koo,5 using a modified “ultra” Goeckerman therapy with narrow-band UVB, showed that this treatment was effective for psoriasis resistant to both prebiologic therapies, such as cyclosporin, methotrexate, or phototherapy, and biologic treatments. The authors compared their results with both biologics and immunemodulators, with PASI 75 as the criterion for efficacy, and showed the superiority of the modified Goeckerman procedure in the induction of remission. For many patients with psoriasis, however, the length of disease-free interval off medication or treatment is just as important a factor in deciding treatment options. Although the decrease in PASI is well documented in the literature, the duration of remission is not, and is the primary objective of this study. Remission rates for Goeckerman treatment from our institution have been reported to be 1.7–1.8 years.6 The treatment itself has not changed appreciably, except that patients are now treated as outpatients in a daycare center, rather than as inpatients, and with 7 days of tar and UVB instead of six. Our results show that the average remission rate of up to 1 year, with some patients, is less than our previous experience of 1.8 years, possibly related to the change from inpatient to outpatient. Other reports in the literature have shown that Goeckerman therapy induces remission for a minimum of 6–8 months,31–33 or up to a year or longer in 75% of 300 patients from two US medical centers.33 Our study showed a similar remission of 9.5 months, with 51% of patients remaining clear for 1 year or longer (only 29% received home UVB). The mean remission in our patients was highest, 12 months, in patients who had received no previous systemic therapies and who underwent home UVB as maintenance, with many patients sustaining this remission for 2 years. Goeckerman therapy can also be used to treat patients who have become resistant to biologic agents.33 In our group, 15 of 51 patients (29%) who had failed biologics responded to Goeckerman treatment. Remission off treatment for biologics has been sporadic in the literature within the context of clinical trials.13–30 Langley and Gordon12 extracted the remission rates from all available clinical trials and summarized them very succinctly in their article. They described in detail the difficulties of comparing off-treatment response between clinical trials because of the different criteria used in each trial. These criteria used endpoints, including a 50% decrease in the previously determined PASI 75 improvement, a 25% decrease, and a global score, the complexity of which need not be repeated here. Despite this, they were able to compare these remissions, and showed that alefacept had the highest length of response duration off treatment at 7–8 months after a 12-week course with patients who started with a percentage BSA similar to that of Goeckerman therapy: “clear” or “almost clear.” This was followed by infliximab at 5 months’ duration, and efalizumab and etanercept at 2–3 months’ duration. For most biologics, long-term continuation of therapy or repeat courses are recommended to maintain remission.12,21,34–38 In addition, studies are emerging with regard to the rebound of psoriasis during treatment, specifically with efalizumab,39 an observation also noted in our patients. The most frequent side-effects of Goeckerman regimens are contact dermatitis and mild local burning as a result of tar hypersensitivity, and the potential for environmental contamination with a tar mutagen.41 The most serious risk after prolonged UVB treatment is the increased potential of skin cancers42 and melanoma, although these remain quite low.40 In a review of the literature from 1966 to June 2002, it was noted that UVB phototherapy was a very safe treatment modality.5,40 Specifically, Pittelkow et al.40 showed that the incidence of skin cancer was not appreciably increased above the expected incidence for the general population. The long-term safety of biologic agents is still unknown. The use of biologics has risks and not all adverse effects are harmless.2,43 There have been reports of the potential to trigger opportunistic infections,43,44 reactivate tuberculosis despite receiving chemoprophylaxis,44 reactivate autoimmune diseases, induce antinuclear antibody (ANA) and anti-DNA antibodies,45 and increase the risk for lymphoma compared with the general population.43 Rare cases of aplastic anemia, pancytopenia, vasculitis, demyelination, and congestive heart failure have been noted.46 In spite of these concerns, they have been used satisfactorily over the past several years;47 however, in contrast with Goeckerman therapy, the longitudinal risks of the continuous administration of biologics remain largely unknown. The Goeckerman procedure is used by many of our patients as a once-yearly treatment, usually in the fall or winter. A 3-week course of Goeckerman treatment costs about $10,000–12,000. This once-yearly therapy can be supplemented with a home UVB treatment which adds $2000 to the cost. When used properly by experienced patients, home UVB can help maintain remission for up to 2 years. The range of cost for an average course of a biologic is between $22,000 and $59,700 per year. Etanercept at 50 mg/mL twice weekly for 3 months, and once per week thereafter as maintenance dose (for 1 year), costs about $25,548 average wholesale price (AWP). Alefacept costs approximately $11,940 for one course of 12 weeks. A second 12-week course leads to a total cost of about $23,880 per year AWP. Because of the expense of biologics and the lack of long-term remissions and the risk of side-effects from immunosuppressants, Goeckerman treatment is becoming a more attractive modality for many patients with moderate to severe psoriasis. One of the main disadvantages of Goeckerman treatment is the time commitment for patients. In our institution, a course of Goeckerman therapy lasts about 3 weeks, requiring close proximity to a major medical center and potential out-of-pocket expenses for patients. Another disadvantage is the decreased disbursement for Goeckerman therapy by insurance companies, which has led to the closure of many such programs nationwide in favor of other, potentially less safe, treatment options. Guidelines in our department, which take into consideration efficacy, safety, and cost, place phototherapeutic options, including Goeckerman treatment, as first-line treatment for moderate to severe psoriasis prior to immunosuppressants or biologics (Fig. 1). The choice of either an immunosuppressant or a biologic is left to the discretion of the physician and patient. These guidelines are similar to the consensus of the Canadian Psoriasis Expert Panel48 and other recommendations in the literature. The guidelines of the Dutch Society of Dermatology and Venereology are more stringent, and state that the use of biologics may be considered when a patient cannot tolerate or is unresponsive to conventional systemic treatment (including phototherapy), or has an increased risk of side-effects.49 Goeckerman treatment is still the first-line therapy for psoriasis in the Czech Republic because of its low cost and long-term efficacy.50 Algorithm for treatment of moderate to severe psoriasis (10% body surface area). BBUVB, broad-band ultraviolet B; NBUVB, narrow-band UVB; PUVA, psoralen plus UVA In conclusion, using standards of efficacy, safety, and cost, the Goeckerman regimen emerges as a standard for psoriasis treatment. It is superior in all criteria of safety and efficacy, in addition to a significant cost benefit.51,52 In answer to those who have asked the question, “Where has Goeckerman gone,”53 we would reply that it is alive and well at our institution. The main objections to Goeckerman therapy remain the time spent in treatment for the patient and the labor-intensive nature of the program for the provider. We recognize that our data have several limitations related to the inherent nature of a retrospective study, namely the subjective information on BSA obtained via a phone call, which did not permit us to calculate PASI scores. Because of the different BSA criteria and different global assessment scales to measure remission in different studies, it is difficult to compare results in the literature. Standardization of these parameters would assist in comparative studies in the future. Finally, a well-designed prospective study of a head-to-head comparison of the cost-effectiveness of biologics and the Goeckerman regimen is needed to validate our data. The authors thank Jane Link, LPN, for her assistance with this study.

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