Psoriasis has a prevalence of approximately 1–2% in the U.K., which translates to as many as 1·2 million affected individuals, and is associated with significant morbidity and consequent economic burden to the health service and society as a whole.1–3 An estimated 25% of patients require secondary care management by a dermatologist1 where treatment options include episodic inpatient admission, day treatment for complex topical therapy, phototherapy and standard systemic therapy (methotrexate, ciclosporin, acitretin). More recently, biologic therapy has become established as an important treatment option in patients with severe psoriasis,3 and now forms part of the standard management paradigm in more than 75% of units in the U.K.4 Biologic therapy is significantly more expensive in terms of drug costs than traditional treatment options, and a shortfall in funding is cited as a major obstacle to prescribing in approximately 40% of dermatology units recently surveyed.4 However, relatively little is known about the total healthcare cost of treating severe psoriasis in daily clinical practice and what the budgetary impacts of such high-cost drugs are when compared with standard systemic therapy. This paucity of information has been identified by the National Institute for Health and Clinical Excellence (NICE)5,6 as an area deserving further research. To address this, we have investigated healthcare resource use in a cohort of patients with severe psoriasis before and after the introduction of biologic therapy at St John’s Institute of Dermatology. This single centre serves a population of 8 million,7 with a tertiary service for patients with moderate to severe psoriasis seeing approximately 150 new patients per year.
Summary Background Biologic therapy has become established as an important treatment option in patients with severe psoriasis, but is significantly more expensive in terms of drug costs than traditional treatment options. Relatively little is known about the total healthcare cost of treating severe psoriasis in daily clinical practice and what the budgetary impacts of such high-cost drugs are when compared with standard systemic therapy.
Objectives To describe the impact of biologic therapy introduction on the use of medical resources, costs and where available, outcomes in patients with moderate to severe psoriasis.
Methods Data were extracted from case notes of a sequential patient cohort with psoriasis attending a tertiary referral severe psoriasis service and initiated on biologics (adalimumab, efalizumab, etanercept or infliximab) for treatment of their psoriasis. Data on hospital resource use (inpatient, outpatient, day ward, accident and emergency visits and phototherapy sessions) and drug usage (systemic nonbiologic and biologic psoriasis therapies and supportive drugs) were collected for 12 months prior to, and at least 6 months following initiation of biologic therapy. Outcome was measured using the Psoriasis Area and Severity Index (PASI). Differences in resource use and associated costs and outcomes, between 12 months before and after initiation of biologic therapy, were tested using Wilcoxon paired sign tests for continuous data and the McNemar test for categorical data. Confidence intervals (CI) around treatment costs were constructed using a 5000-sample bootstrap analysis.
Results The primary analysis population comprised 76 patients completing 12 months of biologic therapy: 71% males; mean age at time of study 47·3 years (range 23–74); mean duration of psoriasis 24·7 years (range 5·3–45·5). Significant reductions (P < 0·05) in the year following initiation of biologic therapy were observed for all hospital resource use categories, with mean annual costs reduced by £1682 (95% CI −3182 to −182·2; P = 0·05). Mean annual drug costs increased by £9456 (95% CI 8732–10 182; P < 0·001). Mean PASI fell by 8·9 points from 18·7 to 9·8 (95% CI −10·8 to −7·1; P < 0·001).
Conclusions Total healthcare costs associated with treatment of severe psoriasis with biologic therapy are significantly greater than with traditional systemic therapy. However, some of these are offset by substantial reductions in the number and length of hospital admissions and use of photo- and systemic therapy, and result in significantly improved patient outcome (as inferred by improvement in PASI).
Materials and methods
This was a retrospective observational review of patients with plaque psoriasis who had been initiated on biologic therapy. The primary objective of the study was to compare healthcare resource use and associated costs in patients with plaque psoriasis for a 12-month period prior to, and for up to 12 months following commencement of first biologic therapy. Secondary outcome measures included comparisons of quality of life (QoL) and disease severity before and after the initiation of biologic therapy.
All patients with psoriasis initiated on a biologic therapy who had attended the specialist psoriasis clinic at St John’s Institute were identified either during clinic attendances and/or from the clinic’s biologics database. To qualify for inclusion, patients had to be aged ≥ 18 years, and been initiated on a biologic therapy for the treatment of psoriasis at least 6 months prior to the commencement of data collection. Patients who had received their biologic therapy as part of a clinical trial were excluded as the purpose of the study was to establish data representative of clinical practice.
All data were captured from the patients’ notes, electronic patient records, pharmacy records and other relevant databases within the Guy’s and St Thomas’ Hospitals NHS Trust. The data collected comprised patient demographics; treatment history (systemic therapy, including biologic therapy, phototherapy, supportive or related therapies); weight at initiation of biologic therapy and last recorded weight; and hospital resource use related either directly or indirectly to psoriasis disease, including management of any treatment-related toxicities [outpatient visits; day ward admissions; inpatient admissions; intensive care unit (ICU) admissions; accident and emergency (A&E) admissions]. Co-morbidities occurring at any time prior to study enrolment were classified according to the British Association of Dermatologists’ Biologic Interventions Register.8 Treatment history and hospital resource use data were collected for 12 months prior to, and 12 months following, the initiation of biologic therapy. For those patients who had received at least 6 months but less than 12 months of biologic therapy, the available treatment history and hospital resource use data were collected. Details of individual data items collected in the study are reported in Table 1. Baseline severity of psoriasis, on initiation of the first biologic, and response to treatment were measured using the Psoriasis Area and Severity Index (PASI). Prior to 2006, the PASI score was not routinely collected and on the day of initiation of biologic therapy, only 16 of 76 patients had a recorded score. Therefore, the PASI score on the nearest date (but not more than 6 months) prior to initiation was taken as the initial score. An average PASI score was then calculated for the period following initiation of biologics. QoL data were measured using the Dermatology Life Quality Index (DLQI). The periods prior to and following initiation of biologics were designated in the same way as for the PASI score. Data were entered directly into a database built in Microsoft Access and checked for accuracy by clinical staff at the St John’s Institute of Dermatology.
|Date of diagnosis|
|Treatment history of systemic therapy, including biologic therapy|
|Dose information (only for drugs received in the year before and year after commencement of first biologic therapy)|
|PASI, assessment dates and scores (only those recorded during the year before and the year after commencement of first biologic therapy)|
|Reason for discontinuation|
|Treatment history of phototherapy|
|Episode of phototherapy|
|Type of phototherapy|
|Number of sessions|
|PASI score before phototherapy|
|Reason for discontinuation|
|Treatment history of supportive or related therapies (e.g. antihypertensive treatment for ciclosporin-induced hypertension)|
|Name of drug|
|Outpatient resource use 12 months before commencement of biologic therapy|
|Outpatient visit number|
|Date of visit|
|Reasons for visit|
|Standard tests and other procedures during visit|
|Day ward resource use 12 months before commencement of biologic therapy|
|Day ward admission|
|Date of admission|
|Reasons for admission|
|Standard tests and other procedures during admission|
|A&E visit resource use 12 months before commencement of biologic therapy|
|A&E visit number|
|Reasons for admission|
|Standard tests and other procedures during A&E visit|
|Inpatient admission resource use 12 months before commencement of biologic therapy|
|Date of admission|
|Date of discharge|
|Reasons for admission|
|Standard tests and other procedures during inpatient admission|
|ICU admission resource use 12 months before commencement of biologic therapy|
|Date of admission|
|Date of discharge|
|Reasons for admission|
|Standard tests and other procedures during inpatient admission|
|Resource use 12 months after commencement of biologic therapy|
|The same resource use data were collected for resource use 12 months after commencement of biologic therapy (or 6 months as appropriate-see methods)|
The study was conducted in accordance with the principles of the Helsinki Declaration (Tokyo Amendment 2004)9 and local research ethics guidelines. The study was approved by St Thomas’ Hospital Research Ethics and Research and Development Committees (EC 08H0802-40).
A sample size of 100 patient records was calculated to be sufficient to detect differences in hospitalization rates before and after biologic treatment at the 5% significance level. This sample size estimate was based on assumed hospitalization rates of approximately 30% for patients on standard systemic therapies and approximately 10–15% for those on biologic therapies. Missing data were coded as such at the data entry stage and the analyses were based only on available data. The data analyses comprised the following:
- 1 Descriptive statistics (means, SDs, etc.) were used to describe frequency of hospitalizations, medical resource utilization (nonbiologic psoriasis drugs, biologic psoriasis drugs and supportive drugs), hospital visits, and associated costs, as well as quality of life and disease severity scores.
- 2 Inferential statistics were used to test differences in resource utilization and associated costs and disease severity between the periods 12 months before and 12 months following initiation of biologic treatment. Because the samples were not independent, paired t-tests were used for continuous normally distributed data, nonparametric Wilcoxon paired signed tests for continuous non-normally distributed data, and McNemar tests for binary data.
- 3 Changes in weight categories between the periods 12 months before and 12 months following the initiation of biologic treatment were tested using the χ2 test.
- 4 A bootstrap analysis was performed on total hospital costs, total drug costs and overall costs for patients with 12 months of data before and after initiation of biologic therapy. Results are based on a bootstrap sample of 5000 repetitions.
The primary analysis population comprised those patients who had complete data for 12 calendar months following commencement of biologic therapy. A secondary analysis was carried out including patients who had completed between 6 and 12 months following commencement of biologic therapy. Because the results and conclusions of this analysis do not differ materially from the primary analysis population, they are not discussed further in this paper but the results for the secondary analysis population are presented in the BJD online appendix (see Supporting information).
Resource use and costs
Costs were estimated from the perspective of the public sector health service in the U.K., using NHS Reference Costs10 and British National Formulary11 unit prices. The costs of home care delivery services provided for adalimumab, efalizumab and etanercept are included in their respective unit costs. Costs are presented in 2008 GBP, and where necessary, inflated to 2008 values using a health-specific inflation factor (using the health-specific consumer price index of 3% representing the annual percentage change in the price of outpatient and inpatient health services between June 2007 and June 200812). Average per patient costs 1 year before and 1 year after commencing biologic therapy were estimated by multiplying resource use reported in the study by the relevant unit costs.
Ninety-six patients met the study inclusion criteria, and 94 records were evaluable. Seventy-six patients had completed records for ≥ 12 months of biologic treatment and these were used for the primary analysis. All analysis results reported hereafter refer to the primary analysis population. Table 2 summarizes demographics and patient characteristics of the primary analysis population. The mean disease duration since diagnosis was 24·7 years, ranging from 5·3 to 45·5 years; the mean time from psoriasis diagnosis to first biologic was 22·1 years; 71% of the study patients were male, with a mean age of 47·3 years.
|Male, n (%)||54 (71)|
|Age, mean (SD, range)||47·3 (11·9, 23–74)|
|Duration from diagnosis to first biologic (in years), mean (SD, range)||22·1 (10·2, 2·7–42·1)|
|Overall disease duration in years (from diagnosis to data collection date), mean (SD, range)||24·7 (10·2, 5·3–45·5)|
Patients had significant co-morbidities. The most frequent co-morbidity was hypertension (64%), followed by psoriatic arthritis (55%), dyslipidaemia (42%), depression (26%) and liver disease (22%). Twelve per cent of patients with psoriasis had diabetes and 10% had skin cancer [squamous cell carcinoma (3%); basal cell carcinoma (7%)].
The majority of patients weighed between 71 kg and 100 kg at their last recorded weight and at the time of first biologic use. There was a statistically significant shift (P < 0·001) towards the higher weight categories between initiation of biologics and the last recorded value (Fig. 1). Twenty per cent of patients weighed more than 100 kg at the date of first biologic use, with 28% weighing more than 100 kg at last recorded weight.
Drug use and associated costs
Table 3 summarizes the number of patients and days of treatment on the systemic therapies before and after commencing biologic therapy, while Table 4 summarizes the number of patients and days of treatment on biologic therapies for 12 months after initiation. Mean treatment days for both the whole analysis population (e.g. mean days on etanercept across all patients) and for those patients receiving the specified biologic only (e.g. for patients receiving etanercept, the mean number of days on etanercept) are reported. In the year following initiation of biologic therapy there was a significant reduction in the number of patients and days of treatment of the nonbiologic, systemic therapies [e.g. ciclosporin, fumaric acid esters (Biogen, Maidenhead, UK) and acitretin]. Use of methotrexate did not decrease significantly, either in number of patients receiving the drug, or in mean number of days of treatment. There was no significant difference in the usage of supportive drugs (such as antivirals, antibiotics and steroids) before and after the initiation of biologic therapy, and the costs associated with supportive drugs were small.
|Systemic drug||Units||Mean resource units (± SE) per patient in the 12 months before initiation||Mean resource units (± SE) per patient in the 12 months after initiation||P-value|
|Acitretin||Number of patients||18||1||< 0·001a|
|Number of days on treatment per patient||58·0 (13·9)||7·6 (5·5)||< 0·001b|
|Ciclosporin||Number of patients||36||17||< 0·001a|
|Number of days on treatment per patient||119·5 (17·3)||36·9 (10·8)||< 0·001b|
|Fumaric acid esters or Fumaderm®c||Number of patients||19||3||< 0·001a|
|Number of days on treatment per patient||45·7 (10·8)||2·9 (1·7)||< 0·001b|
|Hydroxycarbamide||Number of patients||5||0||0·063a|
|Number of days on treatment per patient||15·1 (7·5)||–||–|
|Methotrexate||Number of patients||31||27||0·481a|
|Number of days on treatment per patient||104·3 (17·2)||100·2 (17·3)||0·603b|
|Mycophenolate mofetil||Number of patients||3||0||0·250a|
|Number of days on treatment per patient||2·6 (1·8)||–||–|
|Biologic therapy||Units||Mean days on treatment (± SE) per patient in the 12 months after initiation|
|All patientsa||Patients treated with the specified biologic|
|Adalimumab||Number of patients||6|
|Number of days on treatment per patient||15·9 (7·5)||201·0 (56·0)|
|Efalizumab||Number of patients||9|
|Number of days on treatment per patient||18·5 (8·3)||156·0 (52·8)|
|Etanercept||Number of patients||54|
|Number of days on treatment per patient||229·3 (18·6)||322·8 (10·9)|
|Infliximab||Number of patients||24|
|Number of days on treatment per patient||82·2 (16·1)||260·4 (25·5)|
Table 5 details the costs associated with all classes of drug therapies prescribed 12 months before and 12 months after the initiation of biologic therapies. Overall drug costs increased significantly, by approximately £9500 (P < 0·001) following the initiation of biologic therapy. There was a significant decrease in costs associated with systemic and supportive therapies between the 12 months before and 12 months after the initiation of biologic therapy. This contributed a modest cost offset of approximately £1000 against the additional cost of biologic drug therapy.
|Resource||Daily cost of treatment (£)||Unit cost per mga (£)||Mean cost £ (± SE) per patient in the 12 months before initiation||Mean cost £ (± SE) per patient in the 12 months after initiation||P-value|
|Total biologics||–||10 423·3 (370·4)|
|Acitretin||1·90||0·04||81·0 (20·3)||10·1 (7·7)||< 0·001c|
|Ciclosporin||5·25||0·02||628·9 (97·5)||212·5 (67·7)||< 0·001c|
|Fumaric acid esters||14·82||0·021||509·5 (150·6)||43·8 (25·7)||< 0·001c|
|Methotrexate||0·07||0·05||15·5 (3·4)||11·9 (6·2)||0·144c|
|Mycophenolate mofetil||10·07||0·003||10·8 (7·2)||–|
|Total systemic drugs||1249·4 (179·5)||278·2 (70·9)||< 0·001c|
|Flucloxacillin||–||0·004||0·74 (0·74)||4·63 (2·96)||0·314c|
|Prednisolone||–||0·01||0·15 (0·12)||0·18 (0·17)||1·000c|
|Rifinah 300®d||–||0·0009||–||0·28 (0·28)|
|Total supportive drugs||1·14 (0·77)||5·50 (3·29)||0·744c|
|Total||1250·5 (179·5)||10 707·0 (396·2)||< 0·001c|
Hospital resource use and associated costs
Figure 2 summarizes hospital admissions by ward type, and Table 6 details the associated costs, 1 year before and 1 year after the initiation of biologic therapy. Inpatient admissions were significantly less frequent (P < 0·035) and significantly less costly (P < 0·005) in the 12 months after the initiation of biologic therapy. Furthermore, the average length of inpatient stay was significantly longer in the 12 months preceding biologic therapy initiation, than in the 12 months following first treatment (P = 0·005). There was no difference in the frequency of outpatient admissions in the 12 months before and after the first biologic therapy. However, day ward admissions were more frequent (P < 0·001) in the 12 months after biologic therapy initiation. Ninety-one per cent of day ward admissions following initiation of biologic therapy were in patients receiving infliximab at the time. Conversely, the number of phototherapy sessions was significantly less frequent in the 12 months after the first biologic therapy. There were no ICU or high dependency unit admissions. For day ward admissions and phototherapy, there was a significant difference in the cost 1 year before and 1 year after biologic therapy initiation. For day ward admissions there was a significant increase in cost (P < 0·001), and for phototherapy a significant decrease in cost (P = 0·033). Overall, mean hospital costs decreased by £1625 in the year following initiation of biologic therapy (P = 0·028).
|Resource||Unit cost (£)||Mean cost £ (± SE) per patient in the 12 months before initiation||Mean cost £ (± SE) per patient in the 12 months after initiation||P-value|
|Inpatient admissions||291 per day||1887·7 (578·4)||451·8 (206·3)||0·005a|
|ICU admissions||1072 per day||–||–|
|HDU admissions||676 per day||–||–|
|A&E visits||86 per visit||2·26 (2·26)||3·39 (2·52)||0·569a|
|Outpatient visits||72 per visit||232·1 (8·0)||234·0 (6·8)||0·726a|
|Day ward admissions||441 per admission||63·8 (22·9)||510·6 (98·1)||< 0·001a|
|Phototherapy||283 per session||770·8 (336·0)||74·5 (74·5)||0·033a|
|Totalb||2956·7 (758·8)||1274·3 (240·2)||0·028|
Figure 3 provides a summary of mean hospital and drug costs 12 months prior to, and 12 months following biologic therapy initiation. There was a significant reduction in costs associated with hospital use (P = 0·028), but a significant increase in drug costs (P < 0·001). Overall, there was a significant increase in mean cost per patient of £7774 in the 12 months after biologic therapy initiation.
Impact of biologic therapy on disease severity and quality of life
Overall, the mean PASI score fell by 8·9 points from 18·7 to 9·8 (P < 0·001) (Table 7). A lower PASI score indicates lower severity of disease, and therefore a significant improvement in mean PASI score was observed following the initiation of biologic therapy. Because DLQI data were not collected routinely for much of the data collection period, there were insufficient data to conduct a meaningful analysis.
|Period||n||Mean PASI||95% CI||P-valuea|
|Difference||69||–8·9 (0·9)||–10·8 to –7·1||< 0·001|
This study evaluates medical resource use patterns in a patient population being treated in a tertiary level clinic for severe psoriasis. Our data indicate that the overall costs associated with psoriasis treatment significantly increased after the introduction of biologic therapy, and that most of this increased cost related to drug costs. However, this increase in cost was offset by significantly reduced costs associated with major changes in the pattern of healthcare delivery. Notably, the introduction of biologic therapy more than halved the number of patients requiring inpatient admission, and reduced the mean number of inpatient days by more than 75%. Reductions in the use of nonbiologic systemic drugs, particularly ciclosporin and fumaric acid esters, and in phototherapy sessions, were also observed. Importantly, biologic therapy delivered a significant improvement in disease severity in our patient cohort. While the degree of improvement was less than that reported in randomized controlled trials (RCTs), this may reflect a relatively treatment-resistant group (failed prior systemic therapy) and/or differences between real life and highly controlled clinical trial settings. Furthermore, a proportion of patients were maintained successfully on ciclosporin and methotrexate but were switched to biologic therapies because of toxicity. For these patients, the benefit of biologic therapy is successful control of psoriasis disease without, for example, the impact on renal function associated with ciclosporin, which would not be reflected in an improvement in PASI score. In addition, the data were not accrued in a prospective manner and included a historical cohort (prior to 2006) where PASI scores were not routinely recorded. Likewise, QoL data were only sporadically collected and it was therefore not possible to evaluate any potential QoL benefits alongside the observed improvements in disease severity.
The patterns of biologic drug use we observed reflect the availability of each drug during the time period of data collection (2003–08). Our data also indicate that in general, etanercept is used continuously, rather than, as indicated by the license until very recently, intermittently. This reflects the fact that patients with chronic severe disease require ongoing, long-term disease control, with evidence from use of infliximab and etanercept that improvement in QoL and satisfaction with treatment is greater with continuous vs. intermittent therapy.13,14 While the conclusions that can be drawn regarding the shift in weight distribution are limited, the findings are of interest, one interpretation being that tumour necrosis factor antagonist therapy leads to an increase in weight, and are consistent with previous observations.15,16
Psoriasis is associated with significant morbidity and economic burden to the health service.1–3 While there may be periods of spontaneous remission for varying periods of time, in general the disease is chronic and persistent.3 Indeed, in the current study, mean time since diagnosis until initiation of biologic treatment was 22 years, with a maximum of 42 years. The high prevalence of co-morbidities observed in this patient cohort appears consistent with findings from other groups, indicating a patient group representative of severe psoriasis patients in general.17 The prevalence of liver disease (22%) is also consistent with methotrexate therapy18 and perhaps more importantly the increased prevalence of nonalcoholic fatty liver disease in patients with severe psoriasis that is linked to the metabolic syndrome.19
This study does have some important limitations. The retrospective observational design limited data collection to what were available in the patient records. Also, the data relate to a single tertiary level setting, and may not be generalizable to other care settings. Furthermore, the study evaluates data from relatively soon after the introduction of biologic therapy in psoriasis, where patient selection may have resulted in a cohort that has necessarily been exposed to multiple, prolonged traditional systemic therapy. Initiation of biologic therapy in current cohorts may occur earlier in the treatment pathway than previously, given the wider provision of funding following NICE approval and increasing clinical experience and familiarity with biologic treatments among dermatologists.
This study did not attempt to estimate the wider impact on improvements in psoriasis disease severity on nonmedical resources and society, for example, those associated with improved employment opportunities. Productivity has been observed to improve in patients receiving biologic treatment in a RCT population.20 Further research is warranted to evaluate such societal costs and outcomes in a real-world patient population. The related, equally important question from a health economics point of view is whether these new biologic therapies offer real value for money. The data accrued in our study include only limited information on outcomes and thus preclude formal health economic analysis, but will enable future evaluations to include more robust data on baseline treatment costs.
In conclusion, this study has provided detailed information on the use of medical resources in a moderate to severe psoriasis population not receiving biologic therapy. This will be of value in cost-effectiveness evaluations of biologic therapies and examination of optimal treatment pathways for patients with this condition. Furthermore, the study demonstrates a reduction in hospital and nonbiologic systemic drug use associated with improvement in disease severity following use of biologic drugs in a severe psoriasis cohort. While acquisition costs of biologic drugs are high in comparison with conventional systemic therapies, some cost offsets are achieved due to the significant impact of these new treatments on psoriasis disease severity and reduction in hospital resource use.
What’s already known about this topic?
• Biologic therapy is an established treatment option in patients with severe psoriasis, and forms part of the standard management paradigm in more than 75% of units in the U.K.
• It is significantly more expensive in terms of drug costs than traditional treatment options, and funding is cited as a significant obstacle to prescribing in approximately 40% of dermatology units recently surveyed.
What does this study add?
• This study will be of value in cost-effectiveness evaluations of biologic therapies and examination of optimal treatment pathways for patients with psoriasis.
• The study demonstrates a reduction in hospital and nonbiologic systemic drug use associated with improvement in disease severity following use of biologic drugs in a cohort of patients with severe psoriasis.
The authors acknowledge financial support from the Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy’s and St Thomas’ NHS Foundation Trust in partnership with King’s College London and King’s College Hospital NHS Foundation Trust. This study was sponsored by Janssen Cilag Limited. The authors thank Christina Donatti and Aurea Duran of IMS Health for their support in editing the manuscript.