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Infliximab treatment improves productivity among patients with moderate-to-severe psoriasis

European Journal of Dermatology. Volume 17, Numéro 5, 381-6, September-October 2007, Investigative report

DOI : 10.1684/ejd.2007.0234

Summary

Auteur(s) : Kristian Reich, Frank O Nestle, Ying Wu, Mohan Bala, Debra Eisenberg, Cynthia Guzzo, Shu Li, Lisa T Dooley, Christopher EM Griffiths , Department of Dermatology, Georg-August University; Von-SieboldStrasse 3, 37075, Göttingen, Germany, St John’s Institute of Dermatology, King’s College London School of Medicine at Guy’s, King’s College & St Thomas’ Hospitals, Floor 8 Guy’s Tower, Guy’s Hospital, London SE1 9RT, United Kingdom, Centocor, Inc., 200 Great Valley Parkway, Malvern, PA 19355, United States, The Dermatology Centre, The University of Manchester, Hope Hospital, Stott Lane, Salford, Manchester, M6 8HD, United Kingdom.

Illustrations

ARTICLE

Auteur(s) : Kristian Reich¹, Frank O Nestle², Ying Wu³, Mohan Bala³, Debra Eisenberg³, Cynthia Guzzo³, Shu Li³, Lisa T Dooley³, Christopher EM Griffiths⁴

¹Department of Dermatology, Georg-August University; Von-SieboldStrasse 3, 37075, Göttingen, Germany
²St John’s Institute of Dermatology, King’s College London School of Medicine at Guy’s, King’s College & St Thomas’ Hospitals, Floor 8 Guy’s Tower, Guy’s Hospital, London SE1 9RT, United Kingdom
³Centocor, Inc., 200 Great Valley Parkway, Malvern, PA 19355, United States
⁴The Dermatology Centre, The University of Manchester, Hope Hospital, Stott Lane, Salford, Manchester, M6 8HD, United Kingdom

accepté le 18 Avril 2007

Psoriasis affects approximately 2% of the population. The affected individuals, many of who are of working age, experience severe physical discomfort and impaired quality of life. The psychological impact of psoriasis on patient quality of life has been well documented [1, 2]. Patients suffer from a variety of psychosocial burdens, including stigmatization, stress, depression, and other psychosocial co-morbidities [3]. The severity of depression may be significant, as highlighted by a recent study reporting that over 5% of patients had active suicidal ideation [4].As further evidence of the profound emotional and social impact of psoriasis, the perception of general health and social functioning was shown to be affected to a greater degree in individuals with moderate-to-severe psoriasis than in those with certain other chronic diseases, including hemophilia, hypertension, back pain, and arthritis [5]. In a survey conducted by the National Psoriasis Foundation, 79% of 6,194 patients with severe psoriasis reported that psoriasis had a negative impact on their lives [6]. Taken together, these findings underscore the significant psychosocial burden associated with psoriasis.The physical manifestations and psychological effects of psoriasis can result in missed days of work and decreased productivity at work. In a survey in the United Kingdom among patients with severe psoriasis, Finlay et al. found that 59.3% of those who were employed had missed an average of 26 workdays during the preceding year due to their psoriasis. Among patients who were not working, 33.9% attributed not working to their psoriasis [7]. An analysis of a nationwide survey in the United States (US), which included 1,127 psoriasis patients, found that psoriasis had a significant negative impact on work and productivity. Compared with matched controls, psoriasis patients were more likely to report missing more than one day of work, having impaired productivity at work, and having more impairment of activities other than work, all due to health reasons [8]. Other studies have also demonstrated a reduction in work productivity and social functioning in patients with mild, moderate, or severe psoriasis [9, 10].The clinical effectiveness of the tumor necrosis factor alpha (TNF-α) inhibitor, infliximab, in psoriasis has now been demonstrated [11-13]. Infliximab given at weeks 0, 2, and 6, and every 8 weeks thereafter significantly and rapidly improved signs and symptoms of psoriasis, as measured by the Psoriasis Area and Severity Index (PASI) [14, 15], and patient health-related quality of life (HRQoL) [16], as assessed by the disease-specific Dermatology Life Quality Index (DLQI) [17] and the generic 36-item Short Form Health Survey (SF-36) [18]. Work productivity in patients with psoriasis, however, has not been studied in a large, placebo-controlled study. We thus analyzed data from a large, randomised, double-blind, placebo-controlled, Phase III study (EXPRESS) to investigate the effects of infliximab therapy on patient productivity. As reported previously [14], data from EXPRESS showed that PASI 75 and PASI 90 responses (i.e., ≥ 75% or ≥90% improvement in PASI scores from baseline, respectively) at week 10 were achieved by significantly greater proportions of patients receiving infliximab compared with those receiving placebo (80.4% vs. 2.6% for PASI 75 and 57.1% vs. 1.3% for PASI 90; both p < 0.001). DLQI scores, physical component summary (PCS) scores, and mental component summary (MCS) scores (mean ± SD changes from baseline) also improved significantly at week 10 for patients receiving infliximab compared with placebo (10.3 ± 7.1 vs. 0.4 ± 5.7 for DLQI scores; 5.0 ± 8.3 vs. – 0.4 ± 7.7 for PCS; 6.3 ± 11.0 vs. – 0.8 ± 9.7 for MCS; p < 0.001 for all comparisons) [16]. Demonstrating improved work productivity in patients with psoriasis would be of value, particularly with regard to the impact of lost productivity on the indirect costs of this chronic disease [19].

Materials and methods

Study design and patients

Study design and eligibility criteria for the Phase III, multicentre, double-blind, placebo-controlled EXPRESS trial have been described elsewhere [14]. The trial was conducted at 32 centres (23 in Europe and 9 in Canada), with the approval of the Institutional Review Boards or Institutional Ethics Committees of all sites. All patients signed an informed consent form before undergoing any trial procedures. Briefly, the study enrolled 378 adult patients who had moderate-to-severe psoriasis and were candidates for phototherapy or systemic therapy. All patients were required to have a PASI score of at least 12 and at least 10% involvement of body surface area (BSA) with psoriasis. Patients were excluded if they had been treated previously with any TNF-α blocking agents or had a history or risk of serious infection, lymphoproliferative disease, or active or latent tuberculosis.

Eligible patients were randomised 4:1 at baseline to receive infliximab or placebo. The infliximab group received intravenous infusions of infliximab 5 mg/kg at weeks 0, 2, and 6, and then every 8 weeks thereafter through week 46. The placebo group received placebo infusions at weeks 0, 2, 6, 14, and 22, and then crossed over in a double-blind fashion to receive infliximab 5 mg/kg at weeks 24, 26, and 30 followed by 5 mg/kg every 8 weeks through week 46. In the infliximab group, placebo infusions were given at weeks 24 and 26 to maintain the blind. PASI was used to assess clinical response [20].

Productivity assessment

Productivity was measured based on several features, using a visual analog scale (VAS) as well as key productivity-related questions from the SF-36 and DLQI. Patients were asked to assess how psoriasis affected their productivity at work, school, or home. The VAS ranges from 0 cm, indicating that productivity was very much impacted by their disease, to 10 cm, indicating that their disease had no impact at all on productivity. The VAS has been used to assess productivity in studies of infliximab in other diseases, including ankylosing spondylitis and psoriatic arthritis [21, 22].

Additionally, the impact of physical health and emotional problems on work or daily activities was assessed using the role-physical and role-emotional domains of the SF-36 questionnaire. The SF-36 is widely used to assess patient HRQoL in several disease states. The SF-36 consists of 8 multi-item domains: physical functioning, role-physical, bodily pain, mental health, role-emotional, social functioning, vitality, and general health. Two summary components of the SF-36, the PCS and the MCS, are derived by aggregating the individual scale scores. The mean (± SD) for the PCS and the MCS scores in the general US population is 50 (± 10) [18]; scores in the European population are similar [23]. Higher scores on the SF-36 summary or domain scores represent better HRQoL.

The role-physical domain of the SF-36 assesses whether physical health in the past 4 weeks had impacted work and other regular daily activities, such as reducing the amount of time the patient spent at work or on other activities, accomplishing less than he/she would like, being limited in the kind of work or other activities, or having difficulty performing their work or other activities. The role-emotional domain assesses whether emotional problems, such as feeling depressed or anxious, in the past 4 weeks had an impact on these aspects of work or other activities.

The DLQI consists of 10 questions that assess the impact of skin disease on six different domains, with possible responses for each question ranging from 0 (“not at all”) to 3 (“very much”). Summing the scores for all questions produces a total DLQI score that ranges from 0 to 30, with lower scores indicating better HRQoL. A DLQI score above “10” indicates a very large effect on HRQoL [24]. Two questions of the DLQI assess the impact of the condition of the skin on working and studying. One question assesses whether the skin condition prevented the patient from working or studying (yes/no). If the answer is “no”, a follow-up question assesses how much the skin condition has been a problem at work or studying (a lot/a little/not at all). The responses to these questions were analyzed to further evaluate the impact of infliximab therapy on the patients’ ability to work or study.

Productivity VAS, SF-36, and DLQI scores were evaluated at baseline and at weeks 10, 24, and 50.

Statistical analysis

The changes from baseline in productivity VAS and SF-36 scores at week 10 and week 24 were compared between the infliximab and placebo groups using a 2-sample t-test on the van der Waerden normal scores. Note that for percent change from baseline in productivity, median (rather than mean) values were deemed the most appropriate summary statistic because the mean values were skewed by large percent changes observed in patients with low productivity scores at baseline. No data were imputed. All analyses were conducted based on available data. The bias resulting from this should be minimal, since few patients had missing data. Changes of a half of a standard deviation were considered clinically significant, where applicable [25]. Spearman’s correlation was used to assess the correlations between productivity VAS and clinical parameters in all patients. All statistical tests were two-sided at an alpha level of 0.05. Statistical analyses were performed using the SAS (Version 8, SAS Institute, Cary, NC).

Results

Baseline characteristics

Baseline clinical and demographic patient characteristics for the EXPRESS study have been reported elsewhere in detail [14]. Briefly, most study participants were male (70.9%), with a mean age of 42.8 years, mean percentage BSA involvement of 34.0%, and mean PASI score of 22.9 at baseline (table 1). All demographic and disease parameters were comparable between treatment groups. At baseline, the mean DLQI score for the study population was elevated at 12.5, and the mean SF-36 PCS and MCS scores were decreased at 45.6 and 45.7, respectively.

The average baseline SF-36 role-physical domain score was low, compared with the US average (65.8 versus 81.0) [26]; this was also true for the role-emotional domain score (72.1 versus 81.0). Baseline productivity data indicated impaired productivity (mean VAS: 5.9 cm), indicating the average self-reported productivity was about 40% below the maximal level of 10 cm (table 1).
Table 1 Baseline characteristics of psoriasis patients in the EXPRESS study

Characteristics	Placebo (n = 77)	Infliximab 5 mg/kg (n = 301)	Total (n = 378)
Age (yrs)
Mean ± SD	43.8 ± 12.6	42.6 ± 11.7	42.8 ± 11.9
Sex, n (%)
Male	61 (79.2)	207 (68.8)	268 (70.9)
Female	16 (20.8)	94 (31.2)	110 (29.1)
Race, n (%)
Caucasian	74 (96.1)	295 (98.0)	369 (97.6)
Black	1 (1.3)	1 (0.3)	2 (0.5)
Asian	2 (2.6)	2 (0.7)	4 (1.1)
Other	0 (0.0)	3 (1.0)	3 (0.8)
BSA (%)
Mean ± SD	33.5 ± 17.5	34.1 ± 19.0	34.0 ± 18.7
PASI score (0-72)
Mean ± SD	22.8 ± 8.7	22.9 ± 9.3	22.9 ± 9.2
DLQI score (0-30)
Mean ± SD	11.8 ± 7.5	12.7 ± 7.0	12.5 ± 7.1
SF-36 PCS (0-100)
Mean ± SD	47.2 ± 9.2	45.2 ± 11.1	45.6 ± 10.8
SF-36 MCS (0-100)
Mean ± SD	45.4 ± 12.5	45.8 ± 11.7	45.7 ± 11.9
SF-36 RP scores
Mean ± SD	69.8 ± 37.7	64.8 ± 41.1	65.8 ± 40.4
SF-36 RE scores
Mean ± SD	71.9 ± 38.6	72.1 ± 38.7	72.1 ± 38.7
Productivity VAS (0-10 cm)
Mean ± SD	6.3 ± 3.2	5.8 ± 3.4	5.9 ± 3.3

Patient disposition

Through week 24, of the 77 patients in the placebo group and 301 patients in the infliximab group, respectively, 3 (3.9%) and 20 (6.6%) discontinued the study agent due to adverse events and 5 (6.5%) and 2 (0.7%) due to unsatisfactory therapeutic effects. Through week 50, the study agent was discontinued in 8 (10.4%) and 34 (11.3%) patients due to adverse events and in 7 (9.1%) and 14 (4.7%) patients due to unsatisfactory therapeutic effects in the placebo crossover and infliximab groups, respectively.

Productivity

Productivity, as measured by the VAS, and the role-physical and the role-emotional domain scores of the SF-36 improved significantly from baseline at weeks 10 and 24 (table 2). At week 10, there was a statistically significant difference in mean change in VAS productivity when comparing the infliximab (2.7 cm increase) and placebo groups (0.1 cm decrease; p < 0.001); this difference was sustained through week 24 (a mean increase of 2.5 cm for infliximab compared with a mean decrease of 0.2 cm for placebo; p < 0.001).

The median percent increase in VAS productivity at week 10 was 22.5% for the infliximab group, as compared with a median percent decrease of 1.1% for the placebo group (p < 0.001). At week 24, the median percent increase was 23.6% for the infliximab group compared with no change for the placebo group (p < 0.001, figure 1).

Similar trends were observed in the SF-36 role-physical and role-emotional domain scores (table 2). Mean role-physical scores in the infliximab and placebo groups, respectively, were 64.8 and 69.8 at baseline, 85.8 and 64.6 at week 10, 83.7 and 67.2 at week 24, and 78.9 and 74.1 at week 50; mean role-emotional scores in the respective groups were 72.1 and 71.9 at baseline, 90.6 and 69.7 at week 10, 89.6 and 70.1 at week 24, and 83.3 and 77.1 at week 50. Detailed analysis of the role-physical and role-emotional domains showed a substantial impact on work or daily activities with infliximab treatment (table 3). The proportion of patients in the infliximab group who stated that physical health had an impact on work or daily activities (i.e., responded “yes” to at least one question in the role-physical scale) decreased from 49.7% at baseline to 20.6% at week 10. Similarly, the proportion of patients who stated that emotional problems affected work or daily activities decreased from 39.3% to 14.8% in the infliximab group through week 10, while modest changes were observed in the placebo group during this period.

At week 50, improvements in both productivity and role-emotional and role-physical scores were sustained with infliximab maintenance therapy (table 2). These changes were consistent regardless of gender. Improvement in these parameters for placebo patients who had crossed over to infliximab at week 24 approached that seen for those receiving infliximab maintenance therapy from baseline.

Based on responses to the DLQI questionnaire at baseline, 12.1% of patients in the infliximab group (n = 36) and 9.1% of those in the placebo group (n = 7) reported that their skin condition prevented them from working or studying at baseline. The proportion decreased to 1.4% (n = 4) at week 10 in the infliximab group, while a small increase (to 11.6%; n = 8) was observed in the placebo group. Among patients who stated that their skin condition prevented them from working at baseline, 84.9% of patients in the infliximab group (n = 28) stated that their skin condition no longer prevented them from working at week 10, compared with 42.9% of those in the placebo group (n = 3; p < 0.01).

Among patients who had stated that their skin condition did not prevent them from working or studying at baseline, 60.2% of those in the infliximab group (n = 133) and 47.3% of those in the placebo group (n = 26) still reported that their skin condition was a problem while working or studying. Among the subset of patients who had stated that their skin condition had been a problem while working or studying at baseline, 87.7% of those in the infliximab group (n = 107) stated that their skin condition was no longer a problem while working or studying at week 10, compared with 17.7% of those in the placebo group (n = 3; p < 0.001).
Table 2 Mean (± SD) improvement from baseline in productivity and SF-36 role-physical and role-emotional domain scores through week 50 by visit; randomised psoriasis patients in the EXPRESS study

	Placebo-Infliximab Crossover (n = 77)	Infliximab 5 mg/kg (n = 301)	p-value
Productivity VAS^a
Week 10	– 0.1 ± 2.9	2.7 ± 3.5	< 0.001
Week 24	– 0.2 ± 3.2	2.5 ± 3.5	< 0.001
Week 50	1.9 ± 3.6	2.0 ± 3.4	NA
SF-36 RP scores^a
Week 10	– 5.2 ± 35.0	20.6 ± 37.8	< 0.001
Week 24	– 2.6 ± 35.5	18.5 ± 39.8	< 0.001
Week 50	4.3 ± 36.7	13.5 ± 39.6	NA
SF-36 RE scores^a
Week 10	– 2.2 ± 28.3	18.2 ± 39.2	< 0.001
Week 24	– 1.7 ± 33.3	16.5 ± 38.0	< 0.001
Week 50	5.2 ± 41.9	10.8 ± 36.6	NA

^{^a}At weeks 0, 10, 24, and 50, respectively, productivity VAS scores were available for 374, 366, 352, and 352 patients and RE and RP scores were available for 375, 369, 353 and 356 patients.

Table 3 Detailed SF-36 role-physical and role-emotional response at week 10^a

Domain and questions	Placebo		Infliximab
Baseline	Week 10	Baseline	Week 10
Role-physical:
Impact of physical health on work or daily activities	46.8	45.1	49.7	20.6
Cut down time spent on work or other activities	20.8	22.5	29.2	11.3
Accomplished less than one would like	36.4	35.2	41.6	15.5
Limited in the kind of work or other activities	31.2	33.8	32.9	12.7
Had difficulty performing work or other activities	32.5	35.2	37.3	14.8
Role-emotional:
Impact of emotional problems on work or daily activities	40.3	39.4	39.3	14.8
Cut down time spent on work or other activities	23.4	26.8	23.5	8.6
Accomplished less than one would like	31.2	32.4	34.2	12.0
Didn’t do work or other activities as carefully as usual	29.9	21.1	25.8	7.2

^{^a}Values for specific questions are the percentages of patients who answered “yes”. Values for impact of physical health or emotional problems on work or daily activities are the percentages of patients who answered “yes” to at least one of the questions associated with that domain.

Correlation between VAS and clinical parameters

Significant correlations were observed in the change from baseline to week 10 between productivity VAS and both PASI (r = – 0.33; p < 0.001) and DLQI (r = –0.58; p < 0.001) scores. Figure 2 shows the decline in productivity with increasing PASI scores in all patients.

Discussion

Using data from patients with moderate-to-severe psoriasis from the large, Phase III EXPRESS study, we show that infliximab therapy is associated with significant improvement in patient productivity as measured by the 10-cm VAS and selected SF-36 domain scores and DLQI responses. The strengths of our study include the large sample size, the placebo-controlled design, and the comprehensive measurement of productivity by analysis of key productivity-related questions as well as productivity VAS data.

Although several biologics have been approved for treating psoriasis, this is the first study to demonstrate an association between reducing the signs and symptoms of moderate-to-severe psoriasis and improving patient productivity. Data generated from this study may have economic implications as we further investigate the financial burden of psoriasis. Few cost-of-illness studies have been conducted for psoriasis. Moreover, the cost estimates derived from published studies vary from approximately $1 billion to more than $4 billion per annum in the US. Several years ago, Krueger et al. estimated the combined cost of hospitalization and outpatient therapy to be approximately $1.6 billion [27]. A more recent cost-of-illness analysis of psoriasis in the US found that the direct medical cost of psoriasis was much lower, about $650 million [28]. A recently reported cost-of-illness study in Germany found that the mean total cost was euro 6,709 per patient per year; these patients had a mean PASI score of 18.2. These costs were higher in “high-need” patients (euro 8,831; PASI score of 22.2) [19]. The indirect costs of psoriasis, including the economic impact of work days lost and reduced productivity while at work, however, have not been well studied and can be substantial. Thus, the total cost of psoriasis to society could be much higher. In this study, we have confirmed the negative impact of psoriasis on patients’ work and productivity and have demonstrated that infliximab therapy significantly improved self-reported productivity among patients with moderate-to-severe psoriasis. Further studies are needed to evaluate the economic value of such improvement.

The productivity VAS used in this study has already been used in two infliximab studies in other indications. In ASSERT, a Phase III, randomised, placebo-controlled trial assessing the efficacy and safety of infliximab in patients with ankylosing spondylitis, van der Heijde et al. found that the productivity VAS increased significantly compared with placebo in patients who received infliximab 5 mg/kg at weeks 0, 2, 6, and every 6 weeks thereafter through week 24 [21]. Mean productivity (as measured by the VAS) in the infliximab group increased from 4.2 at baseline to 6.4 at week 24, compared with an increase from 4.3 to 5.1 in the placebo group. In IMPACT 2, a large clinical trial involving patients with psoriatic arthritis, a similar improvement in productivity was observed [22].

At week 50, improvements in productivity and role-emotional and role-physical scores were sustained with infliximab maintenance therapy. For placebo patients who had crossed over to infliximab at week 24, improvements in productivity and role-emotional and role-physical scores approached those seen in patients who had received infliximab maintenance therapy from baseline. These scores improved after initially worsening relative to baseline at weeks 10 and 24 but remained lower in the placebo crossover patients compared with infliximab-randomised patients at week 50. With continued infliximab therapy, the scores in placebo-randomised patients would be expected to improve to levels similar to those of infliximab-randomised patients.

The current data provide further support for the association between disease severity and the productivity VAS. Among patients with more severe psoriasis (PASI >15), the negative impact on productivity was more pronounced when compared with those who had less severe disease (figure 2). However, an impaired productivity was also noted in patients with a PASI of 5 or less, suggesting that maximal clearance of psoriasis is an important treatment goal. Results of this investigation and those reported from the IMPACT 2 study [22] confirm that infliximab therapy not only improves skin and joint symptoms, but also at least partially normalizes productivity in patients with psoriasis or psoriatic arthritis.

It may be regarded as a limitation of the study that productivity was assessed using self-reported parameters such as the VAS and role-physical and role-emotional domains of the SF-36. However, previous studies provide support for construct validity and sensitivity to change of the productivity VAS [21, 22]. These studies found a strong correlation between the productivity VAS and parameters of clinical disease severity and quality of life, supporting the validity of this instrument in assessing productivity. The correlation between the productivity VAS and both PASI response and DLQI results in this study further support the validity of the VAS. Not only did the VAS correlate with disease severity in the current study, but the magnitude of the correlation fell within the range of patient-reported productivity scores in previous studies [29, 30]. Furthermore, the role-emotional and role-physical scores of the SF-36 have been shown to correlate with employment outcomes [31].

In examining the improvement in productivity scores observed in this study, it is important to assess whether these changes are clinically meaningful. The improvement in productivity VAS exceeds half the baseline standard deviation, which has been found to correspond to the threshold for meaningful change for patient reported outcomes. Further, the percent improvement from baseline of 22.5% also allows us to interpret the magnitude of benefit. Changes in the role-emotional and role-physical scales were also clinically meaningful based on the change of approximately 1/2 of the baseline standard deviation [25]. Further studies that attempt to directly observe productivity improvements will be needed to confirm the observation of this study, although such studies are both challenging to undertake and methodologically complex.

In summary, using data from a large clinical trial, we found that productivity was impaired in a large sample of patients with active moderate-to-severe plaque psoriasis and significantly improved during treatment with infliximab, parallel to the reduction in psoriasis signs and symptoms and the improvement of HRQoL parameters. The beneficial effect of infliximab on patients’ productivity was observed at week 10 and largely sustained during maintenance therapy for up to one year. Because loss of productivity is an important contributor to the indirect costs of psoriasis, our findings may be relevant for the pharmacoeconomic assessment of treatments such as infliximab. However, more research is needed to quantify the economic burden of psoriasis, including the impact of diminished work productivity, and to more fully understand the effect of therapeutic intervention.

Acknowledgements

Financial Support: Centocor and Schering-Plough Corp. supported this study. Conflicts of Interest: Employment: Drs. Bala, Wu, Guzzo, and Dooley and Ms. Li and Ms. Eisenberg (Centocor, a Johnson & Johnson company), Dr. Guzzo (previous employee of Merck), and Dr. Wu (previous employee of Bristol-Meyers Squibb); Consultancies: Dr. Reich (Abbott, Biogen-Idec, Centocor, Schering-Plough, Essex, Serono, Wyeth), Dr. Nestle (Centocor, Schering-Plough, Serono, Biogen-Idec, Genentech, Galderma), and Dr. Griffiths (Abott, Serono, Biogen, Novartis, Centocor, Schering-Plough, Wyeth, Novo Nordisk, Astra-Zeneca, UCB-Celltech, Galderma); Honoraria: Dr. Reich (Abbott, Biogen-Idec, Centocor, Schering-Plough, Essex, Serono, Wyeth), Dr. Nestle (Centocor, Schering-Plough, Serono, Biogen-Idec, Genentech, Galderma), and Dr. Griffiths(Schering A.G., Essex Pharma, Stiefel, Amgen, Serono, Wyeth, Syngento); Stock ownership or options: Drs. Wu, Bala, Guzzo, and Dooley and Ms. Li (Johnson & Johnson) and Dr. Guzzo (Merck); Expert testimony: Dr. Griffiths (Serono); Grants: Dr. Reich (Biogen-Idec), Dr. Nestle (Schering-Plough, Biogen-Idec), Dr. Griffiths (Serono, Wyeth, Schering-Plough, Novartis, Leo, Galderma, Stiefel, Biogen, Genmab, Syngenta); Patents: Dr. Guzzo (a method for treating pediculosis capitis infestation); Patent applications: None; Royalties: None.

Editorial support: We are indebted to C. Arnold and J. Barrett, of Centocor.

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