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Comparative effectiveness of biological therapies on improvements in quality of life in patients with psoriasis

Summary Background Evidence of the comparative effectiveness of biological therapies for psoriasis on health‐related quality of life (HRQoL) in routine clinical practice is limited. Objectives To examine the comparative effectiveness of adalimumab, etanercept and ustekinumab on HRQoL in patients with psoriasis, and to identify potential predictors for improved HRQoL. Methods This was a prospective cohort study in which changes in HRQoL were assessed using the Dermatology Life Quality Index (DLQI) and EuroQoL‐5D (EQ‐5D) at 6 and 12 months. Multivariable regression models were developed to identify factors associated with achieving a DLQI of 0/1 and improvements in the EQ‐5D utility score. Results In total, 2152 patients with psoriasis were included, with 1239 patients on adalimumab, 517 on etanercept and 396 on ustekinumab; 81% were biologic naïve. For the entire cohort, the median (interquartile range) DLQI and EQ‐5D improved from 18 (13–24) and 0·73 (0·69–0·80) at baseline to 2 (0–7) and 0·85 (0·69–1·00) at 6 months, respectively (P < 0·001). Similar improvements were achieved at 12 months. At 12 months, multivariable regression modelling showed that female sex, multiple comorbidities, smoking and a higher DLQI or a lower EQ‐5D utility score at baseline predicted a lower likelihood of achieving a DLQI of 0/1 or improvement in the EQ‐5D. Compared with adalimumab, patients receiving etanercept, but not ustekinumab, were less likely to achieve a DLQI of 0/1. There was no significant difference between the biological therapies in EQ‐5D improvement. Conclusions In routine clinical practice biological therapies produce marked improvement in HRQoL, which is influenced by the choice of biological therapy, baseline impairment in HRQoL, lifestyle characteristics and comorbidities. These findings should help inform selection of optimal biological therapy for patients related to improvements in HRQoL.

• Earlier observational studies were either cross-sectional, thereby limiting the ability to compare changes in HRQoL, or cohort studies that have not taken into account important clinical factors that could influence treatment response, such as alterations in dosing regimens of biological therapies and the concomitant use of conventional systemic treatments for psoriasis.
What does this study add?
• This large prospective cohort study found that in routine clinical practice, the use of biological therapies for psoriasis was associated with marked improvements in HRQoL over 12 months.
• These improvements were influenced by the choice of biological therapy, baseline impairment in HRQoL, lifestyle characteristics and comorbidities.
• Compared with adalimumab, patients receiving etanercept were less likely to achieve a DLQI of 0/1, but there was no significant difference between ustekinumab and adalimumab in the proportion of patients achieving a DLQI of 0/1.
• There was no significant difference between the three biological therapies in level of improvement in the EQ-5D.
Psoriasis is a chronic immune-mediated inflammatory skin disorder, affecting approximately 0Á9-8Á5% of the population worldwide. 1 Many patients with psoriasis have moderate-tosevere disease that profoundly impacts their emotional wellbeing and health-related quality of life (HRQoL), 2,3 with levels of physical and mental disability comparable with those reported for other major medical disorders such as cancer, diabetes and cardiovascular disease. 4,5 Furthermore, patients with psoriasis have an increased risk of developing comorbid conditions such as psoriatic arthritis (PsA), which can also adversely affect their HRQoL. 6 Biological therapies have revolutionized the treatment of moderate-to-severe psoriasis. The impact of these therapies on HRQoL has been reported in large randomized controlled trials (RCTs). [7][8][9][10][11][12][13] However, there is a lack of head-to-head comparative RCTs assessing the longer-term impact of these therapies on improvements in HRQoL. 12,14 Several meta-analyses have compared the clinical efficacy of different biological therapies for psoriasis, but the results pertain largely to short-term outcomes and do not always reflect findings in clinical practice. [15][16][17][18][19][20][21] The effectiveness of biological therapies on disease activity in routine clinical practice has been demonstrated in several prospective observational cohort studies, with up to 80% of patients achieving at least a 75% improvement in the Psoriasis Area and Severity Index (PASI 75). [22][23][24][25][26][27][28][29] However, evidence of the effectiveness of biological therapies on HRQoL in routine clinical practice is limited to a few observational studies that were either cross-sectional, thereby limiting the ability to compare changes in HRQoL, 30,31 or cohort studies that did not take into account important clinical factors that could influence treatment response. 32,33 Such factors include alterations in dosing regimens of biological therapies over time and the concomitant use of conventional systemic therapies for psoriasis.
The British Association of Dermatologists Biologic Interventions Register (BADBIR) is a U.K. and Republic of Ireland prospective, longitudinal pharmacovigilance register of patients with psoriasis receiving either biological or conventional systemic therapies. Due to its large size, rigorous data collection process, detailed collection of patient demographic characteristics and treatment regimens, and high external validity through participation of 153 dermatology centres, 34 the register represents an ideal resource to assess the impact of biological therapies on HRQoL in patients with psoriasis in routine clinical practice. In this longitudinal observational study, we examined the comparative effectiveness of adalimumab, etanercept and ustekinumab on improvements in HRQoL in patients with psoriasis, and identified factors associated with these improvements.

Materials and methods
The BADBIR, established in September 2007, compares a cohort of patients with psoriasis on biological therapies to a similar cohort on conventional systemic therapies. Full details on the design of the BADBIR and the disease characteristics of its participants have been published previously. 34,35 Baseline assessment Baseline data were collected with patient consent and included patients' demographic characteristics and comorbidities, year of disease onset, standardized measures of health status using self-reported outcome measures [Dermatology Life Quality Index (DLQI) and EuroQoL-5D (EQ-5D)], and detailed information about the patients' current and previous treatment for psoriasis. Details of the comorbidities were classified using the Medical Dictionary for Regulatory Activities system. 36

Follow-up assessments
Data from patients were collected 6 monthly during the study period. Details of the biological therapies, including any change in the dose or therapy, and start and stop dates, were recorded. Information on any new concomitant systemic therapies for psoriasis and their start and stop dates were also captured. Patient questionnaires also recorded DLQI and EQ-5D at 6-and 12-month follow-up.

Study population
Subjects in this study were selected from the August 2015 data cut-off. Hence the study time-frame was from September 2007 to August 2015. Adult patients with chronic plaque psoriasis, receiving adalimumab, etanercept or ustekinumab with follow-up data of ≥ 6 months were included. The start of observation time was the start date of the index biological therapy (therapy received at enrolment). Only the first biological therapy started during registry participation was analysed. Patients were classified as either biologic na€ ıve or non-na€ ıve based on their previous exposure to biological therapies prior to registration into the BADBIR. Evaluations were limited to patients who had a valid baseline DLQI (no more than one question left unanswered) and/or EQ-5D questionnaire (fully completed) recorded within 6 months prior to the start of the index biological therapy and who had another completed questionnaire recorded within 4-8 months and/or 10-14 months (representing the 6-and 12-month follow-ups, respectively) after the start of the index biological therapy ( Fig. S1; see Supporting Information).

Outcome measures
The DLQI consists of 10 questions evaluating the impact of skin disease on six aspects of HRQoL: symptoms and feelings, daily activities, leisure, work or school performance, personal relationships and treatment. 37,38 The total score ranges from 0 to 30, with a score of 0-1 indicating no impairment in HRQoL and higher scores indicating greater impairment. 39 A decrease of ≥ 4 points is considered clinically meaningful. 40 The EQ-5D consists of five dimensions that define health: mobility, self-care, activities, pain/discomfort and anxiety/depression. 41 Responses to questions yield a utility score that ranges from -0Á59-1Á00, where 0 represents death, 1 represents full health, and negative values represent health states that are valued as worse than death, 42 with a change of 0Á05 points considered clinically meaningful. 43

Statistical analyses
The primary outcome measures were the change in (i) the DLQI total and individual domain scores and (ii) the EQ-5D profile and utility score from baseline to 6 and 12 months. The proportion of patients who achieved a DLQI of 0/1 at each time point was also assessed. Secondary outcomes included the proportion of patients who achieved an improvement of ≥ 4 and ≥ 0Á05 points in the DLQI and EQ-5D utility scores, respectively, at 6 and 12 months.
Patients were assigned to one of three unique biological cohorts based on their index biological therapy, and recorded as either biologic na€ ıve or non-na€ ıve. The Wilcoxon signedrank test was performed to examine differences in the DLQI total and domain scores and EQ-5D utility score between baseline and follow-up results. The McNemar v 2 -test was used to examine differences in the proportion of patients reporting any problems in EQ-5D dimensions between baseline and follow-up results.
Predictors of change in the EQ-5D utility score and likelihood of achieving a DLQI of 0/1 were identified at 6 and 12 months using linear and logistic regression models, respectively. An a priori list of covariates was determined to examine potential predictors of response (as presented in Table 5). Adalimumab (the most commonly prescribed biological therapy in the BADBIR) was used as the reference biological therapy to which the others were compared. 44 Concurrent use of methotrexate, ciclosporin and/or other conventional systemic therapies was analysed as a binary variable (ever exposed/ never exposed) throughout the study. Dosing patterns of biological therapy were examined using the time-trend method, which compares the annual cumulative dose patients received to the annual recommended cumulative dose according to product prescribing information. 45 The DLQI and EQ-5D analyses were conducted primarily on an intention-to-treat basis, using any questionnaire recorded at the appropriate time points after the start of the index biological therapy whether or not the patient was still taking the same biological therapy. Sensitivity analyses in which patients who remained on their index biological therapy when the questionnaires were recorded were also conducted (treatment completers only). Given the large cohort studied and multiple statistical tests, a threshold of P ≤ 0Á01 was considered to be statistically significant. All calculations were performed using Stata v.14Á0 (StataCorp, College Station, TX, U.S.A.).

Results
In total, 2152 patients with psoriasis (adalimumab 1239, etanercept 517 and ustekinumab 396) were included ( Fig. S1; see Supporting Information). The mean (AE SD) age of patients, and disease duration were 45Á2 AE 12Á4 years and 22Á4 AE 12Á1 years, respectively; 39Á4% were female. Mean body mass index (BMI) was 31Á1 AE 7Á3 kg m À2 , with 46Á9% having a BMI ≥ 30 kg m À2 . Overall, 73Á4% of patients had one or more comorbidities. Baseline demographic and disease characteristics are summarized in Table 1.
Significant improvements were also achieved within 6 months of treatment in all of the six DLQI domains (Fig. 1). Similar response rates were observed at 12 months. The median values of the DLQI total and individual domain scores for each biological cohort, over the 12 month follow-up period, are presented in Table 2.

Improvements in the EuroQol-5D
The median (IQR) EQ-5D utility score for the entire cohort improved from 0Á73 (0Á59-0Á80) at baseline to 0Á85 (0Á69-1Á00) at 6 months [median change 0Á07 (0-0Á273); P < 0Á001], with 54Á2% of patients achieving a clinically meaningful change of ≥ 0Á05 points. Similar response rates were found at 12 months (Table 4). The proportion of patients reporting any problems in the EQ-5D dimensions was significantly reduced from baseline at 6 months. The greatest decrease for the entire cohort was in the pain/discomfort dimension (from 74Á5% to 44Á6%; P < 0Á001), whereas the smallest was found in the self-care dimension (from 18Á0% to 12Á5%; P < 0Á001). Similar decreases in dimension scores were also found at 12 months (Fig. 2). The median values of the EQ-5D utility scores and the proportions of patients reporting any problems in the EQ-5D dimensions for each biological cohort over the 12month follow-up period are shown in Table 4. Data are presented as n (%) unless otherwise stated. BMI, body mass index; IQR, interquartile range; DLQI, Dermatology Life Quality Index; EQ-5D, EuroQol-5D. a Had a complete DLQI (only one question left unanswered) and/or EQ-5D (no question left unanswered) questionnaire recorded within 6 months prior to the start of the index biological therapy, as well as had another complete DLQI and/or EQ-5D questionnaire recorded within 4-8 months (representing the 6-month follow-up) and/or 10-14 months (representing the 12-month follow-up) after the start of the index biological therapy. b Ever used conventional systemic therapies concomitantly with a biological therapy throughout the study period of 12 months. c Includes any of acitretin, fumaric acid esters and hydroxycarbamide.

Sensitivity analyses
Sensitivity analyses were performed to investigate improvements in the DLQI and EQ-5D among patients who remained on their index biological therapy at the time the DLQI and/or EQ-5D questionnaires were recorded. In total, 1294 and 942 patients were included in the DLQI sensitivity analyses at 6 and 12 months, respectively; 1222 and 887 patients were included in the EQ-5D analyses. Compared with the intentionto-treat analyses, a total of 160 and 245 patients were excluded from the DLQI sensitivity analyses at 6 and 12 months, respectively; 136 and 221 patients were excluded from the EQ-5D analyses because they discontinued their index biological therapy at the time the questionnaires were recorded. Results from the sensitivity analyses did not change the main findings as the magnitude of the improvements observed in the DLQI (Table S1 and S2; see Supporting Information) and EQ-5D (Table S3; see Supporting Information) were consistent with the main analyses. Likewise, results from the multivariable regression models yielded similar predictors to the main findings (Table S4; see Supporting Information).

Discussion
This large prospective cohort study found that in routine clinical practice, the use of biological therapies for psoriasis is To alter the scale for each of the symptoms and feelings, daily activities, leisure and personal relationships domains, the score was divided by 6 (the maximum possible score), and for each of the work or school performance and treatment domains, the score was divided by 3 (the maximum possible score) (Intention-to-treat analysis). associated with marked improvements in HRQoL over 12 months. Improvements were influenced by several factors including the choice of biological therapy, baseline impairment in HRQoL, smoking and presence of comorbidities. Compared with adalimumab, patients receiving etanercept, but not ustekinumab, were less likely to achieve a DLQI of 0/1, but there was no significant difference between the three biological therapies in improvement in the EQ-5D. For the DLQI and the EQ-5D, a change of 4 and 0Á05 points, respectively, correlates with a minimum clinically important difference (MCID). 40,43 The median differences observed in this cohort study were greater than the MCID at both 6 and 12 months' follow-up.
Interestingly, we found that the effectiveness of biological therapies in patients in the BADBIR was less than their reported efficacy in RCTs. For example, the proportion of patients achieving a DLQI of 0/1 in RCTs was 54Á4% for etanercept and 57Á4% for ustekinumab, 7,46 compared with 29Á5% and 46Á8% of patients on etanercept and ustekinumab at 6 months in this cohort study. Furthermore, results from RCTs indicated that EQ-5D change was between 0Á12 and 0Á21, 7,47,48 compared with a change between 0Á07 and 0.11 for EQ-5D at 6 months in the present study. This is likely to be due to differences in demographic and disease characteristics of patients with psoriasis commencing biological therapies in routine clinical practice compared with those enrolled into a clinical trial. 35 Our findings are in line with those reported by Norlin et al., 32 who did not find significant differences in change in the EQ-5D between different biological therapies. However, by comparison, our study has important strengths: the sample size was much larger and we accounted for important clinical factors including smoking and the presence of comorbidities other than PsA. In contrast to our study, Gelfand et al. 30 and Takeshita et al. 31 reported that absolute differences in the DLQI were small and not statistically significant across adalimumab, etanercept and ustekinumab. However, the cross-sectional design of these studies limits the ability to assess changes in response to therapy. Strober et al. 33 reported that improvements in the DLQI from baseline to 6 and 12 months were significantly better in the ustekinumab group than that in the adalimumab and etanercept groups. However, this study did not adjust for important clinical factors that could influence treatment response, such Table 4 Values of the EuroQol-5D (EQ-5D) utility scores and proportions of patients reporting any problem in the EQ-5D dimensions in patients with psoriasis at different follow-up times (Intention-to-treat analysis) We have shown that patients on etanercept, but not ustekinumab, were less likely to achieve a DLQI of 0/1 compared with those on adalimumab. This finding aligns with other studies reporting that patients are more likely to discontinue etanercept due to ineffectiveness compared with adalimumab or ustekinumab. 44 Nevertheless, we found no significant difference between the three biological therapies in improvement in the EQ-5D. Compared with the EQ-5D, the DLQI is a dermatology-specific measure that is more relevant to psoriasis. Hence, the DLQI may have a greater ability to measure specific impairments resulting from the disease and detect smaller changes in health relative to the EQ-5D. 49 However, the use of a generic utility instrument (EQ-5D) allows comparison across different diseases and calculation of quality-adjusted life years, which will provide valuable data to support cost-effectiveness analysis. 50 To our knowledge, this is the first study that has reported on the impact of biological therapies on HRQoL assessed using both a dermatology-specific measure and a generic utility instrument.
We found that patients who discontinued their biological therapy were less likely to show improvements in HRQoL compared with those who continued therapy. This observation suggests that drug survival is an important proxy marker of effectiveness and real-world utility. 44,51 Our study also reports that patients with lower HRQoL (higher DLQI/lower EQ-5D) at baseline were significantly less likely to achieve a DLQI of 0/1 or show improvement in the EQ-5D. This finding acknowledges that the 'cumulative life course impairment' from living with psoriasis may be a selfperpetuating social disconnection and failure to achieve 'full life potential' in some patients, despite receiving effective therapy. 5,52 Hence, the devastating impact psoriasis can have on self-esteem and identity underscores the availability of patient support and psychological treatment as part of routine care. 53 Consistent with previous studies, 54 we found that being a current smoker was a predictor of poor improvement in HRQoL, whereas being an ex-smoker did not predict change in HRQoL, suggesting that smoking could influence response to biological therapies. As the BADBIR was established primarily as a pharmacovigilance register, there are some limitations to studying the impact of biological therapy on HRQoL that should be considered in interpreting our findings. Firstly, information on patients' adherence to treatment was not available. Furthermore, as data were collected on a 6-monthly basis, the study design prevents a more detailed analysis of the time to initial improvement in HRQoL. It has been suggested, in a Swedish Table 5 Multivariable regression analyses of potential factors associated with achieving a Dermatology Life Quality Index (DLQI) of 0/1 and changes in the EuroQol-5D (EQ-5D) utility score at 6 and 12 months (Intention-to-treat analysis) Achieving a DLQI of 0 or 1 a Change in the EQ-5D utility score b 6 months 12 months 6 months 12 months Demographics Age (years) c 0Á97 (0Á87-1Á09) 1Á04 (0Á92-1Á19) À0Á016 (À0Á029 to À0Á004)* -0Á015 (-0Á027 to -0Á002)* Female 0Á91 (0Á72-1Á15) 0Á71 (0Á54-0Á93)* À0Á019 (À0Á046 to 0Á008) 0Á005 (À0Á025 to 0Á035) Obesity status d Obese (BMI ≥ 30 kg m À2 ) 0Á76 (0Á60 to 0Á96)* 0Á78 (0Á60 to 1Á02) À0Á036 (À0Á062 to À0Á010)* À0Á012 (À0Á041 to 0Á018) Missing 1Á00 (0Á59 to 1Á71) 0Á99 (0Á58 to 1Á69) 0Á012 (À0Á048 to 0Á072) À0Á004 (À0Á075 to 0Á067) Smoking status e Ex-smoker 0Á94 (0Á70 to 1Á26) 0Á77 (0Á55 to 1Á07) À0Á019 (À0Á050 to 0Á012) 0Á006 (À0Á029 to 0Á041) Current smoker 0Á83 (0Á61 to 1Á13) 0Á61 (0Á43 to 0Á87)* À0Á047 (À0Á081 to À0Á012)* À0Á021 (À0Á061 to 0Á019) Missing 0Á80 (0Á56 to 1Á13) 0Á66 (0Á45 to 0Á98)* À0Á014 (À0Á053 to 0Á025) 0Á016 (À0Á029 to 0Á061) Comorbidities f Psoriatic arthritis 1Á15 (0Á86 to 1Á52) 1Á09 (0Á79 to 1Á49) À0Á049 (À0Á083 to À0Á014)* À0Á077 (À0Á120 to À0Á034)* 1-2 comorbidities 0Á84 (0Á64 to 1Á10) 0Á51 (0Á37 to 0Á70)* À0Á005 (À0Á023 to 0Á034) À0Á019 (À0Á051 to 0Á013) 3-4 comorbidities 0Á66 (0Á46 to 0Á95)* 0Á49 (0Á32 to 0Á75)* À0Á055 (À0Á100 to À0Á011)* À0Á057 (À0Á107 to À0Á007)* ≥ 5 comorbidities 0Á61 (0Á34 to 1Á11) 0Á39 (0Á20 to 0Á75)* À0Á158 (À0Á232 to À0Á084)* À0Á147 (À0Á217 to À0Á076)* Disease Disease duration (years) c 1Á14 (1Á02 to 1Á27)* 1Á12 (0Á99 to 1Á26) À0Á002 (À0Á014 to 0Á010) À0Á010 (À0Á024 to 0Á003) Baseline DLQI 0Á98 (0Á96 to 0Á99)* 0Á96 (0Á95 to 0Á98)* --Baseline EQ-5D g --0Á037 (0Á031 to 0Á043)* 0Á040 (0Á034 to 0Á046)* Biologic na€ ıve h 1Á23 (0Á91 to 1Á67) 1Á17 (0Á83 to 1Á64) 0Á055 (0Á016 to 0Á094)* 0Á014 (À0Á025 to 0Á053) Concomitant methotrexate i 0Á64 (0Á46 to 0Á88)* 0Á53 (0Á38 to 0Á75)* À0Á036 (À0Á073 to 0Á002) À0Á009 (À0Á046 to 0Á029) Concomitant ciclosporin i 0Á58 (0Á36 to 0Á94)* 0Á70 (0Á42 to 1Á15) 0Á002 (À0Á049 to 0Á054) 0Á004 (À0Á053 to 0Á061) Concomitant other systemics i,j 0Á64 (0Á35 to 1Á18) 0Á60 (0Á32 to 1Á10) À0Á006 (À0Á070 to 0Á058) À0Á007 (À0Á076 to 0Á062) Dosing pattern k CD > RCD 1Á03 (0Á63 to 1Á69) 0Á74 (0Á43 to 1Á29) 0Á026 (À0Á024 to 0Á075) À0Á035 (À0Á092 to 0Á022) CD < RCD 0Á65 (0Á38 to 1Á12) 0Á76 (0Á46 to 1Á26) À0Á070 (À0Á138 to À0Á001)* 0Á003 (À0Á055 to 0Á061) Missing 0Á92 (0Á57 to 1Á48) 0Á87 (0Á50 to 1Á52) 0Á048 (À0Á004 to 0Á099) 0Á028 (À0Á034 to 0Á090) Biological therapy l Etanercept 0Á37 (0Á28 to 0Á50)* 0Á39 (0Á28 to 0Á54)* À0Á031 (À0Á062 to 0Á001) 0Á0003 (À0Á034 to 0Á035) Ustekinumab 0Á86 (0Á59 to 1Á25) 0Á89 (0Á57 to 1Á37) À0Á026 (À0Á069 to 0Á016) À0Á030 (À0Á078 to 0Á019) Stopped index biological therapy m 0Á16 (0Á08 to 0Á32)* 0Á35 (0Á20 to 0Á60)* À0Á077 (À0Á151 to À0Á002)* À0Á059 (À0Á120 to 0Á002) BMI, body mass index; CD, cumulative dose; RCD, annual recommended cumulative dose. a Data are presented as odds ratio (95% confidence interval). b Data are presented as regression coefficient (95% confidence interval). c To evaluate odds ratios and regression coefficients for every 10-year increase in age and disease duration at enrolment into the register, baseline continuous variables of age and disease duration were transformed to age and disease duration divided by 10. At 6 and 12 months, older age at enrolment (by 10 years) was associated with lower improvement in EQ-5D values, and longer disease duration (by 10 years) was associated with higher odds of achieving a DLQI of 0/1. d Reference category: nonobese (BMI < 30 kg m À2 ). e Reference category: never smoker. f Reference category: no comorbidities (excluding psoriatic arthritis). g To evaluate regression coefficients for every 0Á1 point increase in the EQ-5D utility score, the baseline continuous variable of EQ-5D utility score was transformed to EQ-5D multiplied by 10. At 6 and 12 months, higher baseline EQ-5D utility score (by 0Á1 points) was associated with higher EQ-5D values. study of antitumour necrosis factor use in PsA, that utility improvements occur rapidly (within 2 weeks) and are maintained thereafter. 55 An inherent limitation in an observational study is nonrandomization that may introduce selection bias, and although this is partially negated by adjustment for clinically relevant covariates, the presence of unmeasured confounders cannot be discounted. Our results reflect current use of biological therapies for patients with psoriasis in the U.K. and Republic of Ireland, which should be considered in the context of guidelines published by the BAD 56 and the National Institute for Health and Care Excellence for the management of psoriasis. 57 Guidelines for the management of psoriasis are also similar in Scotland 58 and the Republic of Ireland. 59 Our findings also provide a more solid basis for health economic modelling compared with RCT data due to the greater external validity of the BADBIR. 60 Further work is required to investigate whether subsequent switching of biological therapies will predict HRQoL changes. Data from patients with PsA in Sweden suggest that improvements in HRQoL during the first and second courses of biological therapies are similar. 55 Equally important is the need to investigate whether improvements in HRQoL were associated with improvements in disease activity. An earlier study of the PsA cohort within the British Society for Rheumatology Biologics Register found that improvements in HRQoL were significantly associated with improvements in disease activity. 61 In summary, this large prospective cohort study provides novel insights into the extent of improvement in HRQoL in patients with psoriasis receiving treatment with biological therapies in routine clinical practice, and key determinants of treatment response, which are also of particular importance as they support the concept that lifestyle modifications, including smoking cessation, may enhance the effectiveness of biological therapies. These findings should be considered, along with the other known benefits and risks of biological therapies, when choosing the most appropriate treatment for patients with psoriasis.

Supporting Information
Additional Supporting Information may be found in the online version of this article at the publisher's website: Fig S1. Patient selection. Table S1. Values of the Dermatology Life Quality Index total and individual domain scores in patients with psoriasis at different follow-up times [Treatment completers analysis]. Table S2. Proportion of patients achieving a Dermatology Life Quality Index of 0/1 and a clinically meaningful improvement of ≥ 4 points from baseline at different followup times [Treatment completers analysis]. Table S3. Values of the EuroQol-5D (EQ-5D) utility scores and proportions of patients reporting any problem in the EQ-5D dimensions in patients with psoriasis at different follow-up times [Treatment completers analysis]. Table S4. Multivariable regression analyses of potential factors associated with achieving a Dermatology Life Quality Index of 0/1 and changes in the EuroQol-5D utility score at 6 and 12 months [Treatment completers analysis].