Comparison of Treatment Goals between Users of Biological and Non-Biological Therapies for Treatment of Psoriasis in Japan
1
Department of Dermatology, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan
2
Eli Lilly Japan K.K., Akasaka Garden City 13F, 4-15-1 Akasaka, Minato-ku, Tokyo 107-0052, Japan
3
Crecon Medical Assessment Inc., 2-12-15 Shibuya, Shibuya-ku, Tokyo 150-0002, Japan
4
Eli Lilly Japan K.K., Lilly Plaza One Bldg., 5-1-28, Isogamidori, Chuo-ku, Kobe 651-0086, Japan
5
Department of Dermatology, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke 329-0498, Tochigi-ken, Japan
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2021, 10(24), 5732; https://doi.org/10.3390/jcm10245732
Submission received: 12 November 2021
/
Accepted: 29 November 2021
/
Published: 7 December 2021
(This article belongs to the Special Issue Psoriasis and Psoriatic Arthritis: How to Treat in the Era of Biologics and Small Molecule Inhibitors?)
Abstract
:Background: Previously, our cross-sectional observational study in Japan revealed high (68%) discordance within treatment goals between psoriasis patients and their physicians. Objective: This secondary analysis aimed to determine whether patient and physician users of biologics have higher treatment goals than users of non-biologics. Methods: A survey for both patients and physicians on background characteristics, disease severity, treatment goals, treatment satisfaction, and health-related quality of life was conducted at 54 sites. Association between treatment goals and biologic/non-biologic users was assessed using ordinal logistic regression models. Results: In total, 449 patient-physician pairs agreed to participate; 425 completed the survey and were analyzed. More biologic users than non-biologic users reported complete clearance (Psoriasis Area and Severity Index 100) as a treatment goal (patient-reported: 23.6% vs. 16.1%; physician-reported: 26.9% vs. 2.2%). Biologic users were significantly associated with higher treatment goals than non-biologic users (patient-reported: 1.8 (1.15–2.87) (odds ratio (9 5% CI)), p = 0.01; physician-reported: 11.0 (5.72–21.01), p < 0.01). Among biologic users, higher treatment goals were associated with higher treatment satisfaction (patient- and physician-rated); lower treatment goals were associated with back lesions and increasing patient age (patient-rated) and higher disease severity (physician-rated). Conclusion: Use of biologics among patients with psoriasis was associated with higher treatment goals. Further use of biologics contributed to treatment satisfaction. Appropriate treatment goals that are shared among patients and their physicians may improve treatment outcomes.
1. Introduction
Psoriasis is an immune-mediated skin condition that commonly manifests as inflamed, scaly skin lesions [1,2]. Severe symptoms associated with psoriasis are a major contributor to patients’ health-related quality of life (HRQOL) [3,4,5,6]. Biological therapies have emerged as an effective class of treatment for patients with psoriasis that have a significant effect on disease severity [7,8] and are associated with higher levels of treatment satisfaction compared with other therapies [7]. In Japan, the use of biologics is recommended for patients with poor Health Related Quality of Life, HRQOL (Dermatology Life Quality Index (DLQI) score ≥10) [9].
Establishment of treatment goals for patients with psoriasis is considered critical for setting treatment expectations and improving management practices [10]. However, the treatment goals currently recommended in treatment guidelines for psoriasis focus on clinical measures of disease severity and do not take into account other factors such as treatment satisfaction and HRQOL [10,11]. Treatment goals that are aligned between patients and their physicians have the potential to improve treatment outcomes, adherence, and satisfaction [12,13]. Despite this, treatment goals for psoriasis appear to vary widely between patients and their physicians [13,14].
Recently, we conducted a nationwide, cross-sectional observational study in Japan to assess the alignment of treatment goals between patients with psoriasis and their physicians [14]. There was a high level (68%) of discordance of treatment goals between the patient-physician pairs. Factors that contributed most to the discordance were high expectations by patients for complete clearance, and physicians’ perceptions that patients had a low understanding of their treatment options. In addition, we found that more patients in the misaligned group than in the aligned group had not received a prescription for a biologic within the past 2 to 3 weeks (78.3% vs. 66.2%, p = 0.008), suggesting that patient and physician biologic users are more aligned in their treatment goals.
For this secondary analysis, we hypothesized that patient and physician users of biologics have higher treatment goals than non-biologic users. To test this hypothesis, we examined the associations between treatment goals among paired patients and physicians who used biological therapies to treat psoriasis versus those who did not.
2. Materials and Methods
2.1. Study Design
This nationwide, multicenter, cross-sectional observational study was conducted between October 2015 and May 2016 at 54 sites in Japan [14]. The sites included general practitioners, clinics, university hospitals, and private and public hospitals. The study protocol was reviewed and approved by the Ethics Committee of Jichi Medical University, the Central Institutional Review Board of Medical Corporation Ganka-Koseikai, and the relevant local institution ethics committees of each participating hospital. The study protocol was implemented in accordance with the Declaration of Helsinki (2013), the Guidelines for Good Pharmacoepidemiology Practices (2015), the Ethical Guidelines Concerning Medical Studies in Human Subjects in Japan [15], and ethical principles based on the relevant statutes/standards in Japan.
All treatment decisions and clinical assessments were made at the discretion of the treating physicians. Patients who participated in the study gave written informed consent for the collection and use of their information to be included in this study. Informed consent was obtained from patients after physicians had explained the study protocol to the recruited patients. Only patients who gave their informed consent were given the surveys.
2.2. Study Population
Study participants were patients with physician-reported moderate-to-severe psoriasis and a history of systemic treatments, including biological drugs, and their treating physicians. Dermatologists with experience in oral or biological treatments for psoriasis patients were included. Patients were not included in the study if they were participating in a clinical trial, had completed a clinical trial less than 6 months before the current study, or had pustular psoriasis, erythrodermic psoriasis, or psoriatic arthritis.
2.3. Study Survey
As previously reported [14], the survey comprised 52 questions for patients and 31 questions for physicians. The questions were categorized into background characteristics of patients and physicians, disease severity (Patient Global Assessment (PtGA), Physician Global Assessment (PGA)), treatment goals (same question for both patients and physicians), and treatment satisfaction and HRQOL. Measures used for treatment satisfaction and HRQOL included the Treatment Satisfaction Questionnaire for Medication (TSQM) [16], the Treatment Satisfaction scale (numerical rating scale 0 to 10), the DLQI [17], and the Itch Numeric Rating Scale (Itch NRS) [18]. A DLQI score ≥ 10 was considered as one of the measures for moderate-to-severe psoriasis [19,20]. Treatment goals were categorized from 1 (highest goal) to 7 (lowest goal) where 1 = complete clearance (Psoriasis Area and Severity Index (PASI) 100) [21], 2 = almost complete clearance (PASI 90 to <100), 3 = complete clearance at specific sites (nails, head, genitals, other), 4 = improvement from previous treatment but without complete or almost complete clearance, 5 = relief from itchiness, 6 = other goals, and 7 = no particular goal set.
The ordinal scale for understanding of disease and treatment choice ranged from not at all, to does not understand very well, neither, somewhat understands, understands very well.
Patients who qualified for inclusion were recruited into the study by their physicians. Patients were sent a paper-based survey within 2 weeks of enrollment and returned the surveys by mail. Each patient and their treating physician completed the surveys independently. To minimize the potential for selection bias by physicians, patients were enrolled consecutively.
2.4. Statistical Analysis
Variables for each patient-physician pair were grouped into users of biological therapies (biologic users) and those who did not use biological therapies (non-biologic users), and were examined for associations with treatment goals. Biologic users were defined as patients (and their paired physicians) who were currently using a biological drug for treatment of psoriasis or who had used a biological drug within 3 weeks of completing the survey. Analyses comprised the following: Step 1, variables selected from the survey were categorized into biologic user and non-biologic user groups and were evaluated for differences. Categorical variables were evaluated using the chi-square test; continuous variables were evaluated using the Wilcoxon rank-sum test or Student’s t test. Step 2, variables selected from the survey were evaluated by ordinal logistic regression to evaluate any correlations with treatment goals. Step 3, variables that were statistically significant (p < 0.05) in Steps 1 and Steps 2 were included as covariates. Step 4, of the variables identified in Step 3, only one variable was selected for the same survey question and included in the final covariates for the further analyses. A clinician was asked to review the variables and select one variable that made the most clinical sense. The reasons for setting this rule were: (1) to avoid too many covariates in a stepwise multivariate model; and (2) to avoid including multiple answers from the same question in the multivariate analyses which would be difficult to interpret.
The ordinal logistic regression models assessed the association between treatment goals (outcome variable) and biologic users and non-biologic users (explanatory variables), and were adjusted for covariates. Associations between treatment goals and use of biological therapies were reported as odds ratios (OR) and 95% CIs. Differences between groups were regarded as statistically significant for p < 0.05.
All statistical analyses were performed using SAS® Version 9.4 (SAS Institute Inc., Cary, NC, USA).
3. Results
3.1. Variable Selection
The variables used in the patient-reported analyses included lesion site—symptom on “back” (yes/no), TSQM score (ordinal scale), and DLQI scores (ordinal scale) for daily activities, leisure, and personal relationships. The variables included in the physician-reported analyses included lesion site—symptom on “upper limb” (yes/no), physician’s specialty—psoriasis (yes/no), physician’s workplace (categorical scale), physician’s experience with biologics (ordinal scale), physician’s perspective on the patient’s understanding of their disease (ordinal scale) and treatment choice (ordinal scale), PGA disease severity (0 to 5 scale), and Treatment Satisfaction (0 to 10 scale). Patient age was included in both patient- and physician-reported models because of its clinical importance. Physicians and patients with missing data for treatment goal or who responded that the treatment goal was “other” or “no setting” were excluded from these analyses. Physicians and patients with missing data for the selected covariates were excluded.
3.2. Study Population
Of the 449 patient-physician pairs that agreed to participate in the study, 425 (94.7% response rate) completed the survey and were analyzed. Of the included patients, most were male and had a reasonably long disease duration (mean, 18.8 years) (Table 1). For most patients, psoriasis predominantly affected the head, neck, and lower limbs, and most had at least 3% of their body surface area (BSA) affected (Table 1). Most patients were currently being treated with topical medication, and 25.6% of patients were being treated with biologics at the time the survey was conducted. Of the included physicians, most had considerable experience treating patients with psoriasis; 69.6% specialized in psoriasis, 86.8% had 10 or more years’ experience treating patients with psoriasis, and 75.0% saw 20 or more patients per month (Table 2). Treatment Satisfaction and assessment of disease severity (PtGA, PGA) were similar between patients and physicians (Table 1 and Table 2).
Results by Biologic vs. Non-Biologic Users
When patients and their paired treatment physicians were compared by biologic versus non-biologic users, we found the following results. There were statistically significant differences between biologic users and non-biologic users for both patient-reported and physician-reported characteristics (Table 3). Biologic users had significantly higher treatment satisfaction based on TSQM (global satisfaction score; 68.6 vs. 57.3, p < 0.001) and significantly higher HRQOL scores (lower DLQI scores) than non-biologic users (Table 3). Physicians treating biologic users had significantly greater Treatment Satisfaction (7.8 vs. 6.0, p < 0.001) and significantly lower physician-rated disease severity (PGA disease severity 2.0 vs. 2.7, p < 0.001) (Table 3). Significantly more physician biologic users were psoriasis specialists, who worked in university hospital settings and had more years’ experience than non-biologic user physicians.
Biologic users contributed to a small proportion (13.8%, 8/58) of the total number of patients with DLQI score ≥ 10 (one of the criteria for “moderate-to-severe” psoriasis). For patients with a DLQI score ≥ 10, non-biologic users had more severe disease (3.18 vs. 2.25, PGA disease severity) and lower treatment satisfaction (4.50 vs. 5.88, patient treatment satisfaction) than biologic users. For physicians of patients with a DLQI score ≥ 10, non-biologic users had less experience with biologics than biologic users (36% vs. 12.5% of physicians with ≤2 years of experience).
3.3. Treatment Goals by Biologic vs. Non-Biologic Users
Most patients and physicians reported that their treatment goals were to achieve almost complete clearance, irrespective of whether or not they were biologic users (Figure 1). However, patient and physician biologic users had higher treatment goals than non-biologic users (Figure 1). The percentage of patients reporting complete clearance (PASI 100) as a treatment goal was 23.6% for biologic users and 16.1% for non-biologic users. The percentage of physicians reporting complete clearance (PASI 100) as a treatment goal was 26.9% for biologic users and 2.2% for non-biologic users.
3.4. Factors Associated with Treatment Goals by Biologic vs. Non-Biologic Users
Findings from the ordinal analyses showed that patient and physician biologic users were significantly associated with higher treatment goals than their non-biologic user counterparts (Table 4). For patient-reported analyses, biologic users had 1.8-fold higher odds of having higher treatment goals than non-biologic users (OR 1.820 (95% CI 1.154, 2.868), p = 0.01). Higher treatment goals were significantly associated with higher patient-rated TSQM scores (global satisfaction) (Table 4). In contrast, lower treatment goals were significantly associated with the presence of back lesions and increasing patient age (Table 4).
For the physician-reported analyses, biologic users had 11.0-fold higher odds of having higher treatment goals than non-biologic users (OR 10.967 (95% CI 5.723, 21.014), p < 0.001). Higher treatment goals among biologic users were significantly associated with higher physician-rated Treatment Satisfaction, whereas lower treatment goals were associated with higher PGA disease severity (Table 4).
4. Discussion
In our previous primary analysis, which focused on treatment goal alignment and showed that there is a high level of discordance between Japanese patients with psoriasis and their physicians, we showed that patients tended to set higher treatment goals than their physicians and had a greater desire for “complete clearance”, irrespective of treatment received [14]. We also found that there was more treatment goal misalignment (n = 220, 78.3%) than alignment (n = 88, 66.2%) among non-biological users (i.e., patients who had not had a prescription for a biological drug within the previous 2 to 3 weeks) (p = 0.008) [14]. Hence, we extend these findings to show the characteristics of biologic users and non-biologic users and to examine the treatment goals for both patient and physician biologic users versus non-biologic users, adjusted for other factors. In this subgroup analysis of biologic users versus non-biologic users, complete clearance (PASI 100) was reported as a treatment goal for 23.6% and 26.9% of patient and physician biologic users, respectively, compared with 16.1% and 2.2% of patient and physician non-biologic users, respectively. Both patients and physicians who were biologic users set higher treatment goals than non-biologic users. The results of these secondary analyses may explain the difference in treatment goal alignment and misalignment among recent non-biologic users found in the previous primary analysis. Since the introduction of biologics for treating psoriasis, clinicians’ expectations for a successful treatment outcome with biological therapies have increased to “complete” or “almost complete clearance” (PASI > 90) [13]. In addition, patients treated with biologics have greater success achieving their treatment goals [22] and have higher treatment satisfaction compared with other therapies [7,23]. Therefore, given the experience of patients and physicians with biologics, it is likely that both patients and their physicians have higher expectations for treatment success with biologics than with non-biologics.
In our study, there was a larger percentage of male than female patients with psoriasis. In Japan, the higher percentage of males is consistent with the real-world report [1,2,24]. As for how our sample has an even higher percentage of males, it is not known. Although physicians assess the severity of psoriasis based on symptoms and the body area affected, patients can be more focused on the effects of psoriasis on their HRQOL [10,11,25]. Our findings are consistent with this focus on HRQOL in that treatment goals were associated with disease severity and treatment satisfaction for both patient and physician biologic users. At the time this survey was conducted, both patient- and physician-rated disease severity (PtGA, PGA) was lower and treatment satisfaction was higher among biologic users than non-biologic users. This suggests that as disease severity decreases with the use of biologics, treatment satisfaction increases and the clinical improvement experienced by patients translates to greater patient HRQOL.
In the current study, we found that patient biologic users contributed a small proportion (13.8%) of the total number of patients with DLQI scores ≥10, a criterion to be recommended for biological therapies in Japan [9]. Many patients who used non-biologics in our study had high DLQI scores ≥10 and tended to be less satisfied with their treatment than biologic users. In addition, their physicians tended to have less experience with biologics. Together, these data suggest a large number of patients with psoriasis may be undertreated in Japan, despite being eligible for biological therapy.
In the additional analysis in this study focusing on treatment satisfaction misalignment between patient and physician, we reported that “not changing the treatment goal from start of treatment” was a factor in a patient’s treatment satisfaction being higher than that evaluated by the physician [26]. Hence, the importance of the treatment goal leading to satisfactory treatment outcomes would need to be discussed and emphasized.
As this was a nationwide, multicenter, cross-sectional study conducted in real-world clinical practice, the findings are representative of general Japanese patients and their treating physicians. However, there are a few limitations worthy of mention. First, the interpretation of the findings should take into account the cross-sectional design of the study, which limits the strength of any observed associations, the potential for selection bias arising from consecutive enrollment of patients. In a cross-sectional setting, we cannot make an inference on the causal-effect relationships between outcomes of disease state versus setting a high goal and biologics usage. The patient disease state at the time of the survey could have been a result of prior medical interventions. Second, along with setting PASI scores as the treatment goal target, PASI scores would need further validation as a clinically meaningful treatment goal in the future. Although both physicians and patients may consider biologics to have a higher chance of achieving complete or almost complete response, this perspective could be more dominant among physicians. Patients may simply consider the results satisfactory, even being far from complete clearance. Third, as this was a secondary analysis that focused on a comparison between biologic users and non-biologic users, the sample size for some comparisons may not have been sufficiently powered to detect differences between groups. Fourth, since our sample is derived from the Japanese population within the Japanese health care setting, the study should take into consideration that biologics prescribers in Japan are limited to only hospitals or clinics accredited by the Medical Society. Therefore, although patients and their physicians may have higher treatment goals, some prescribers are limited in the use of biologics by this unique Japanese guideline unless there is a solid referral system. In this study, our analysis was to compare “biologic users versus non-biologic users”, and not “biologic accredited versus non-accredited institutions”. We recognized this Japanese health care situation. Therefore, without including the analyses in the main results, we also looked at how the treatment goals performed in the accredited medical institutions versus those in the non-accredited medical institutions. We found that, similar to results in our previous report (5) and in this report, patients and doctors who were biologics users had higher treatment goals (almost complete or complete clearance) than the non-biologic users even when compared only within the accredited institutions (patients: 73% vs. 52%; doctors: 91.4% vs. 41%). In addition, the treatment goal misalignment was higher among pairs of patients and their treating doctors who were not treated with biologics (75%) vs. those treated with biologics (57%) within the accredited institutions. The rate of misalignment among non-biologic users in the accredited institutions (75%) was comparable to the non-biologic users in the non-accredited institutions (69%). Although we found similar trends of treatment goals when comparing the results by categories of biologic accredited institutions, we did not perform in-depth analyses to control the intended associations with other factors due to sample size limitations. Further studies would be needed to further address the differences of treatment goals by health care settings. Finally, while the patient-centric treatment approach is ideal in clinical settings, we should note that treatment satisfaction related to the use of biologics has financial implications to the patients and the health care system or vice versa. This can be a limitation in some health care systems.
In summary, we found that there were differences between biologic users and non-biologic users such as disease severity, physicians’ experience and workplace, and physicians’ perspectives on their patients’ understanding of disease and treatment options. Patients with psoriasis and their physicians who were users of biological therapies shared higher treatment goals after adjustment for contributing factors. Better understanding of treatment goals between patients and their physicians has the potential to contribute to the development of patient-centered goals that can improve treatment outcomes. The results indicate that availability and experience with biologic treatment are elevating treatment goals for both physicians and patients and are addressing unmet treatment needs.
Author Contributions
All authors (Y.O., A.C.T., S.I., H.T.-I. and M.O.) participated in the interpretation of study results and in the drafting, critical revision, and approval of the final version of the manuscript. Y.O. and A.C.T. were involved in development of the study design, Y.O. and M.O. were investigators in the study and were involved in data collection, and S.I. was involved in data collection and conducted the statistical analysis. All authors have read and agreed to the published version of the manuscript.
Funding
This study was sponsored by Eli Lilly Japan K.K., manufacturer of ixekizumab. Medical writing assistance was provided by Serina Stretton, PhD, CMPP of ProScribe–Envision Pharma Group, and was funded by Eli Lilly Japan K.K. ProScribe’s services complied with international guidelines for Good Publication Practice (GPP3). Eli Lilly Japan K.K. was involved in the study design, data collection, data analysis, and preparation of the manuscript.
Institutional Review Board Statement
The study protocol was implemented in accordance with the Declaration of Helsinki (2013), the Guidelines for Good Pharmacoepidemiology Practices (2015), the Ethical Guidelines Concerning Medical Studies in Human Subjects in Japan [15], and ethical principles based on the relevant statutes/standards in Japan.
Informed Consent Statement
Patients who participated in the study gave written informed consent for the collection and use of their information to be included in this study. Informed consent was obtained from patients after physicians had explained the study protocol to the recruited patients. Only patients who gave their informed consent were given the surveys.
Acknowledgments
The authors would like to thank all patients and physicians from the clinics and hospitals across Japan (Appendix A) who generously shared their time to participate in this study.
Conflicts of Interest
Y. Okubo has been a consultant, scientific advisor and/or investigator for Eli Lilly K.K., Kyowa Hakko Kirin Co. Ltd., Mitsubishi Tanabe Pharma Corporation, Maruho Co. Ltd., Celgene K.K., Janssen Pharmaceutical K.K., AbbVie GK, Eisai Co. Ltd., Torii Pharmaceutical Co. Ltd., Leo Pharma A/S, MSD K.K., Boehringer Ingelheim Japan, Inc., Novartis AG, Taiho Pharmaceutical CO., Ltd., and Bristol-Meiers Squibb Company. M. Ohtsuki has been paid as a consultant to AbbVie GK, Boehringer-Ingelheim Japan, Inc., Celgene K.K., Eisai Co. Ltd., Janssen Pharmaceutical K.K., Kyowa Hakko Kirin Co. Ltd., LEO Pharma A/S, Eli Lilly and Company, Maruho Co. Ltd., Novartis AG, Pfizer Inc., Mitsubishi Tanabe Pharma Corporation, Torii Pharmaceutical Co. Ltd., Taiho Pharmaceutical CO., Ltd., Amgen Inc., Sun Pharma Japan Ltd., UCB Japan Co. Ltd., and Bristol-Myers Squibb Company. S. Inoue is an employee of CRECON Medical Assessment Inc.; CRECON Medical Assessment Inc. was paid to conduct the analyses for this report. A.C. Tang is an employee of Eli Lilly K.K. Japan. H. Torisu-Itakura is an employee of Eli Lilly K.K. Japan and is an Eli Lilly stock holder.
Appendix A. List of Participating Institutions
- Department of Dermatology, Asahikawa Medical University
- Department of Dermatology, Jichi Medical University
- Department of Dermatology, Tokyo Women’s Medical University
- Department of Dermatology, School of Medicine, Teikyo University
- Department of Dermatology, Tokyo Medical University
- Department of Dermatology, School of Medicine, Tokai University
- Department of Dermatology, Graduate School of Medicine, Gifu University
- Graduate School of Medical Sciences, Nagoya City University
- Department of Dermatology, School of Medicine, Kindai University
- Department of Dermatology, Graduate School of Medicine, Osaka City University
- Department of Dermatology, Kawasaki Medical School
- Department of Dermatology, Faculty of Medicine, Fukuoka University
- Department of Dermatology, Tokyo Teishin Hospital
- Department of Dermatology, St Luke’s International Hospital
- Department of Dermatology, Yokohama Chuo Hospital
- Public Interest Incorporated Foundation Jiai-kai, Branch of Imamura Hospital
- Department of Dermatology, Ina Central Hospital
- Department of Dermatology, Iida Municipal Hospital
- Department of Dermatology, Osaka Kaisei Hospital
- Medical Corporation Kojin-kai, Sapporo Dermatology Clinic
- Medical Corporation Kojin-kai, Fukuzumi Dermatology Clinic
- Kobayashi Skin Clinic
- Department of Dermatology, EST Clinic
- Sugawara Dermatology Clinic
- Medical Corporation Subaru-kai, Sugai Dermatology Park Side Clinic
- Hattori Dermatology Clinic
- Medical Corporation Koten-kai, Iidabashi Clinic
- Medical Corporation Shohei-kai, Niki Dermatology Clinic
- Clinic of Dermatology, Ningyocho
- Dr. Mariko Skin & Dermatology Clinic
- Tsujimoto Skincare Clinic
- Shirosaki Dermatology & Neurology Clinic
- Kato Dermatology
- Hou Dermatology
- Machino Skin Clinique
- Yasumoto Dermatology Clinic
- Takagi Dermatology Clinic
- Fushimi Skin Clinic
- Omorimachi Dermatology
- Hayashibe Derma Clinic
- Hasegawa Dermatology Clinic
- Medical Corporation Kojin-kai, Ario Sapporo Dermatology Clinic
- Atago Dermatology
- Medical Corporation Shotoku-kai, Hino Clinic
- Nomura Dermatology Clinic
- Zoshiki Dermatology Clinic
- Nakatsu Dermatology Clinic
- Saruwatari Dermatology Clinic
- Kusuhara Dermatology Clinic
- Medical Corporation Shimizu Dermatology Clinic
- Kokubu Clinic, Abashiri Dermatology Clinic
- Nishide Skin Clinic
- Kazama Skin Clinic
- Shimizu Skin Clinic
References
- Kubota, K.; Kamijima, Y.; Sato, T.; Ooba, N.; Koide, D.; Iizuka, H.; Nakagawa, H. Epidemiology of psoriasis and palmoplantar pustulosis: A nationwide study using the Japanese national claims database. BMJ Open 2015, 5, e006450. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ito, T.; Takahashi, H.; Kawada, A.; Iizuka, H.; Nakagawa, H. Epidemiological survey from 2009 to 2012 of psoriatic patients in Japanese Society for Psoriasis Research. J. Dermatol. 2018, 45, 293–301. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hirabe, M.; Hasegawa, T.; Fujishiro, Y.; Kigawa, M.; Fukuchi, O.; Nakagawa, H. Factors associated with quality of life among patients with psoriasis. Comparison between psoriasis-specific QOL measures and generic QOL measures. Nihon Koshu Eisei Zasshi 2008, 55, 65–74. [Google Scholar]
- Mabuchi, T.; Yamaoka, H.; Kojima, T.; Ikoma, N.; Akasaka, E.; Ozawa, A. Psoriasis affects patient’s quality of life more seriously in female than in male in Japan. Tokai J. Exp. Clin. Med. 2012, 37, 84–88. [Google Scholar] [PubMed]
- Okubo, Y.; Arai, K.; Fujiwara, S.; Amaya, M.; Tsuboi, R. Assessment of the quality of life of patients with psoriasis using Skindex-16 and GHQ-28. Jpn. J. Dermatol. 2007, 117, 2495–2505. [Google Scholar]
- Okubo, Y.; Natsume, S.; Usui, K.; Amaya, M.; Tsuboi, R. Low-dose, short-term ciclosporin (Neoral®) therapy is effective in improving patients’ quality of life as assessed by Skindex-16 and GHQ-28 in mild to severe psoriasis patients. J. Dermatol. 2010, 38, 465–472. [Google Scholar] [CrossRef] [PubMed]
- Florek, A.G.; Wang, C.J.; Armstrong, A.W. Treatment preferences and treatment satisfaction among psoriasis patients: A systematic review. Arch. Dermatol. Res. 2018, 310, 271–319. [Google Scholar] [CrossRef] [PubMed]
- Armstrong, A.W.; Betts, K.A.; Signorovitch, J.E.; Sundaram, M.; Li, J.; Ganguli, A.X.; Wu, E.Q. Number needed to treat and costs per responder among biologic treatments for moderate-to-severe psoriasis: A network meta-analysis. Curr. Med. Res. Opin. 2018, 34, 1325–1333. [Google Scholar] [CrossRef] [PubMed]
- Ohtsuki, M.; Terui, T.; Ozawa, A.; Morita, A.; Sano, S.; Takahashi, H.; Komine, M.; Etoh, T.; Igarashi, A.; Torii, H.; et al. Japanese guidance for use of biologics for psoriasis (the 2013 version). J. Dermatol. 2013, 40, 683–695. [Google Scholar] [CrossRef] [PubMed]
- Armstrong, A.W.; Siegel, M.P.; Bagel, J.; Boh, E.E.; Buell, M.; Cooper, K.D.; Duffin, K.C.; Eichenfield, L.F.; Garg, A.; Gelfand, J.M.; et al. From the Medical Board of the National Psoriasis Foundation: Treatment targets for plaque psoriasis. J. Am. Acad. Dermatol. 2017, 76, 290–298. [Google Scholar] [CrossRef] [Green Version]
- Mrowietz, U.; Kragballe, K.; Reich, K.; Spuls, P.; Griffiths, C.E.M.; Nast, A.; Franke, J.; Antoniou, C.; Arenberger, P.; Balieva, F.; et al. Definition of treatment goals for moderate to severe psoriasis: A European consensus. Arch. Dermatol. Res. 2011, 303, 1–10. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Radtke, M.A.; Reich, K.; Spehr, C.; Augustin, M. Treatment goals in psoriasis routine care. Arch. Dermatol. Res. 2015, 307, 445–449. [Google Scholar] [CrossRef] [PubMed]
- Brezinski, E.A.; Armstrong, A.W. Strategies to maximize treatment success in moderate to severe psoriasis: Establishing treatment goals and tailoring of biologic therapies. Semin. Cutan. Med. Surg. 2014, 33, 91–97. [Google Scholar] [CrossRef] [PubMed]
- Okubo, Y.; Tsuruta, D.; Tang, A.C.; Inoue, S.; Torisu-Itakura, H.; Hanada, T.; Ohtsuki, M. Analysis of treatment goal alignment between Japanese psoriasis patients and their paired treating physicians. J. Eur. Acad. Dermatol. Venereol. 2018, 32, 606–614. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ministry of Education, Culture, Sports, Science and Technology. Ethical Guidelines Concerning Medical Studies in Human Subjects. 2015. Available online: http://www.lifescience.mext.go.jp/files/pdf/n1500_02.pdf (accessed on 18 April 2018).
- Atkinson, M.J.; Sinha, A.; Hass, S.L.; Colman, S.S.; Kumar, R.N.; Brod, M.; Rowland, C.R. Validation of a general measure of treatment satisfaction, the Treatment Satisfaction Questionnaire for Medication (TSQM), using a national panel study of chronic disease. Health Qual. Life Outcomes 2004, 2, 12. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Finlay, A.Y.; Khan, G.K. Dermatology Life Quality Index (DLQI)—A simple practical measure for routine clinical use. Clin. Exp. Dermatol. 1994, 19, 210–216. [Google Scholar] [CrossRef] [PubMed]
- Kimball, A.B.; Naegeli, A.N.; Edson-Heredia, E.; Lin, C.Y.; Gaich, C.; Nikaï, E.; Wyrwich, K.; Yosipovitch, G. Psychometric properties of the Itch Numeric Rating Scale in patients with moderate-to-severe plaque psoriasis. Br. J. Dermatol. 2016, 175, 157–162. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Finlay, A.Y. Current severe psoriasis and the rule of tens. Br. J. Dermatol. 2005, 152, 861–867. [Google Scholar] [CrossRef]
- Okubo, Y. Hands-on practice manual-illustrations & visual- 46: Plaque psoriasis. Clin. Derma. 2011, 13, 3–6. Available online: http://www.tokyo-med.ac.jp/derma/content/files/topics_okubo_2011clinicalderma.pdf (accessed on 17 June 2018). (In Japanese).
- European Medicines Agency (EMEA); Committee for Medicinal Products for Human Use (CHMP). Guideline on Clinical Investigation of Medicinal Products Indicated for the Treatment of Psoriasis. 2004. Available online: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003329.pdf (accessed on 19 April 2018).
- Lambert, J.; Ghislain, P.D.; Lambert, J.; Cauwe, B.; Van den Enden, M. Treatment patterns in moderate-to-severe plaque psoriasis: Results from a Belgian cross-sectional study (DISCOVER). J. Dermatol. Treat. 2017, 28, 394–400. [Google Scholar] [CrossRef]
- Ichiyama, S.; Ito, M.; Funasaka, Y.; Abe, M.; Nishida, E.; Muramatsu, S.; Nishihara, H.; Kato, H.; Morita, A.; Imafuku, S.; et al. Assessment of medication adherence and treatment satisfaction in Japanese patients with psoriasis of various severities. J. Dermatol. 2018, 45, 727–731. [Google Scholar] [CrossRef] [PubMed]
- Kamiya, K.; Oiso, N.; Kawada, A.; Ohtsuki, M. Epidemiological survey of the psoriasis patients in the Japanese Society for Psoriasis Research from 2013 to 2018. J. Dermatol. 2021, 48, 864–875. [Google Scholar] [CrossRef] [PubMed]
- Strohal, R.; Prinz, J.C.; Girolomoni, G.; Nast, A. A patient-centred approach to biological treatment decision making for psoriasis: An expert consensus. J. Eur. Acad. Dermatol. Venereol. 2015, 29, 2390–2398. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Okubo, Y.; Torisu-Itakura, H.; Hanada, T.; Aranishi, T.; Inoue, S.; Ohtsuki, M. Evaluation of treatment satisfaction misalignment between Japanese psoriasis patients and their physicians—Japanese psoriasis patients and their physicians do not share the same treatment satisfaction levels. Curr. Med. Res. Opin. 2021. epub ahead of print. [Google Scholar] [CrossRef] [PubMed]
Figure 1.
Patient- and physician-reported treatment goals. Goal 1 = complete clearance (Psoriasis Area and Severity Index (PASI) 100) [21], Goal 2 = almost complete clearance (PASI 90 to <100), Goal 3 = complete clearance at specific sites (nails, head, genitals, other), Goal 4 = improvement from previous treatment, but without “complete” or “almost complete clearance”, Goal 5 = relief from itchiness, Goal 6 = other goals, and Goal 7 = no particular goal set. (a) A larger number of patient (23.6% vs. 16.1%) and (b) physician (26.0% vs. 2.2%) among biologic users had higher treatment goals of achieving complete clearance.
Figure 1.
Patient- and physician-reported treatment goals. Goal 1 = complete clearance (Psoriasis Area and Severity Index (PASI) 100) [21], Goal 2 = almost complete clearance (PASI 90 to <100), Goal 3 = complete clearance at specific sites (nails, head, genitals, other), Goal 4 = improvement from previous treatment, but without “complete” or “almost complete clearance”, Goal 5 = relief from itchiness, Goal 6 = other goals, and Goal 7 = no particular goal set. (a) A larger number of patient (23.6% vs. 16.1%) and (b) physician (26.0% vs. 2.2%) among biologic users had higher treatment goals of achieving complete clearance.
Table 1.
Patient characteristics.
| Variable | Value (n = 414) 5 |
|---|---|
| Male, % | 74.9% |
| Age (range), y | 56.2 ± 13.9 (20.0–93.0) |
| BMI (range), kg/m2 | 24.3 ± 4.6 (16.0–54.9) |
| Age at disease onset (range), y | 37.2 ± 16.2 (0.0–81.0) |
| Age at disease diagnosis (range), y | 40.0 ± 16.2 (4.0–81.0) |
| Disease duration from onset (range), y | 18.8 ± 11.7 (0.0–65.0) |
| Body part affected (top 3 nominated) | |
| Lower limbs | 78.0% |
| Head | 70.8% |
| Back | 67.1% |
| Body surface area affected 1 | |
| <1% | 24.4% |
| 1–2% | 22.0% |
| 3–10% | 37.0% |
| >10% | 16.5% |
| Current treatment received 2 | |
| Topical | 82.4% |
| Oral | 53.6% |
| Ultraviolet light | 19.1% |
| Biologic | 25.6% |
| Other | 1.4% |
| Treatment Satisfaction 3 | 6.75 ± 2.27 |
| PtGA disease severity 4 | 2.54 ± 1.26 |
1 Palm size is equivalent to 1%; 2 multiple answers were allowed; 3 0 = lowest treatment satisfaction, 10 = highest treatment satisfaction; 4 0 = lowest, 5 = highest severity, all values are mean ± standard deviation unless otherwise indicated. BMI, body mass index; PtGA, Patient Global Assessment; y, year. 5 Out of the total sample (n = 425), 9 pairs were excluded where patient treatment goal information was missing and 2 pairs were excluded where physician treatment goal information was missing.
Table 2.
Physician characteristics.
| Variable | Value 5 (n = 70) |
|---|---|
| Male, % | 64.3% |
| Age (range), y | 50.6 ± 11.7 (30.0–80.0) |
| Specialty 1 Psoriasis Allergy Other | 69.6% 40.6% 41.8% |
| Treatment experience with psoriasis 2 <2 y 2 ≤ 4 y 4 ≤ 6 y 6 ≤ 8 y 8 ≤ 10 y ≥10 y | 0.0% 2.9% 5.9% 4.4% 0.0% 86.8% |
| Number of patients seen per month 2 <5 5–9 10–14 15–19 ≥20 | 1.5% 5.9% 10.3% 7.4% 75.0% |
| Treatment Satisfaction 3 | 6.46 ± 2.08 |
| PGA disease severity 4 | 2.51 ± 1.15 |
1 Multiple answers were allowed; 2 physician responses with obvious errors and inconsistencies were excluded from the analyses; 3 0 = lowest treatment satisfaction, 10 = highest treatment satisfaction; 4 0 = lowest severity, 5 = highest severity. 5 The total number of physicians (n = 70) paired to 425 patients. All values are mean ± standard deviation (range) unless otherwise indicated. PGA, Physician Global Assessment; y, year.
Table 3.
Comparison of patient- and physician-reported characteristics between biologic users and non-biologic users.
Table 3.
Comparison of patient- and physician-reported characteristics between biologic users and non-biologic users.
| Characteristic 1 | Biologic Users | Non-Biologic Users | p 2 |
|---|---|---|---|
| Patient-reported | n 1 = 104 | n 1 = 292 | |
| Patient age, y | 56.3 ± 15.1 | 55.9 ± 13.4 | 0.807 |
| Lesion site, back, n (%) | 54 (51.9) | 211 (72.3) | <0.001 |
| TSQM score (global satisfaction) | 68.6 ± 19.6 | 57.3 ± 17.1 | <0.001 |
| DLQI | |||
| DLQI total score | 3.2 ± 5.0 | 5.0 ± 5.3 | <0.001 |
| Daily activities | 0.5 ± 1.3 | 1.0 ± 1.5 | <0.001 |
| Leisure | 0.5 ± 1.1 | 0.7 ± 1.3 | 0.044 |
| Personal relationships | 0.2 ± 0.9 | 0.4 ± 1.1 | 0.028 |
| Physician-reported | n 2 = 107 | n 2 = 309 | |
| Patient age, y | 56.9 ± 15.2 | 56.4 ± 13.8 | 0.709 |
| Location of lesion (upper limb), n (%) | 42 (39.3) | 229 (74.1) | <0.001 |
| Physician’s specialty—psoriasis, n (%) | 99 (92.5) | 231 (75) | <0.001 |
| Physician’s workplace, n (%) | <0.001 | ||
| Clinic | 35 (32.7) | 202 (65.4) | |
| University hospital | 47 (43.9) | 81 (26.2) | |
| Other | 25 (23.4) | 26 (8.4) | |
| Physician’s experience—biologics, n (%) | <0.001 | ||
| None | 0 (0.0) | 77 (24.9) | |
| <1 y | 0 (0.0) | 10 (3.2) | |
| 1 ≤ 2 y | 9 (8.4) | 25 (8.1) | |
| 2 ≤ 3 y | 4 (3.7) | 14 (4.5) | |
| 3 ≤ 4 y | 13 (12.2) | 19 (6.2) | |
| 4 ≤ 5 y | 35 (32.7) | 58 (18.8) | |
| >5 y | 46 (43) | 106 (34.3) | |
| Physician’s perspective on patient’s understanding of disease, n (%) | 0.001 | ||
| Understands very well | 42 (39.3) | 64 (20.7) | |
| Somewhat understands | 55 (51.4) | 215 (69.6) | |
| Neither | 7 (6.5) | 27 (8.7) | |
| Does not understand very well | 3 (2.8) | 3 (1.0) | |
| Does not understand at all | 0 (0.0) | 0 (0.0) | |
| Physician’s perspective on patient’s understanding of treatment choice, n (%) | <0.001 | ||
| Understands very well | 45 (42.1) | 69 (22.3) | |
| Somewhat understands | 49 (45.8) | 209 (67.6) | |
| Neither | 10 (9.4) | 27 (8.7) | |
| Does not understand very well | 3 (2.8) | 4 (1.3) | |
| Does not understand at all | 0 (0.0) | 0 (0.0) | |
| PGA disease severity | 2.0 ± 1.5 | 2.7 ± 1.0 | <0.001 |
| Treatment Satisfaction (0–10 scale) | 7.8 ± 1.7 | 6.0 ± 2.0 | <0.001 |
1 From the total 425, the number of biologic and non-biologic user pairs that remained in patient-reported analyses was n = 396. (The following were excluded: 9 pairs with missing patient treatment goal information, 20 pairs with patients who reported treatment goal as “other” or “no setting”). 2 From the total 425, the number of biologic and non-biologic user pairs in physician-reported analyses was n = 416. (The following were excluded: 2 pairs with missing information on treatment goal and 7 pairs who reported that the treatment goal was “other” or “no setting”). Categorical variables were compared using the chi-square test and continuous variables were compared using the t test or Wilcoxon rank-sum test. Data are mean (standard deviation) unless otherwise indicated. DLQI, Dermatology Life Quality Index; PGA, Physician Global Assessment; TSQM, Treatment Satisfaction Questionnaire for Medication; y, years.
Table 4.
Regression analysis of factors associated with treatment goals.
| Variables 1,2 | Odds Ratio (95% CI) | p |
|---|---|---|
| Patient-reported variables v 3 | n = 383 | |
| Biologic vs. non-biologic | 1.820 (1.154, 2.868) | 0.010 |
| Age, y | 0.983 (0.970, 0.997) | 0.016 |
| Lesion site, back | 0.544 (0.358, 0.825) | 0.004 |
| TSQM score (global satisfaction) | 1.014 (1.002, 1.026) | 0.021 |
| DLQI score | ||
| Daily activities | 1.106 (0.900, 1.360) | 0.336 |
| Leisure | 1.132 (0.886, 1.446) | 0.321 |
| Personal relationships | 1.085 (0.858, 1.373) | 0.497 |
| Physician-reported variables 4 | n = 413 | |
| Biologic vs. non-biologic user | 10.967 (5.723, 21.014) | <0.001 |
| Patient age, y | 1.003 (0.989, 1.017) | 0.664 |
| Location of lesion (upper limb) | 0.870 (0.549, 1.377) | 0.552 |
| Physician’s specialty—psoriasis | 1.042 (0.602, 1.803) | 0.884 |
| Physician’s workplace | ||
| University hospital | 0.696 (0.429, 1.128) | 0.141 |
| Other | 0.663 (0.342, 1.284) | 0.223 |
| Physician’s experience—biologics | 1.096 (0.991, 1.212) | 0.073 |
| Patient’s understanding of disease (physician perspective) | 1.390 (0.839, 2.303) | 0.202 |
| Patient’s understanding of treatment choice (physician perspective) | 0.631 (0.386, 1.032) | 0.067 |
| PGA disease severity | 0.720 (0.584, 0.887) | 0.002 |
| Treatment Satisfaction | 1.285 (1.139, 1.449) | <0.001 |
1 From the n = 396 of Table 3, 383 remained in the analyses (13 pairs that had missing covariate information were excluded). 2 From the n = 416 of Table 3, 413 remained in the analyses (3 pairs that had missing covariate information were excluded). 3 p values for differences in treatment goals between biologic and non-biologic users were calculated using an ordinal logistic regression model adjusted for age (y), lesion site—back (yes/no), TSQM score (ordinal scale), and DLQI scores (ordinal scale). 4 p values for differences in treatment goals between biologic and non-biologic users were calculated using an ordinal logistic regression model adjusted for age (y), lesion site—upper limb (yes/no), Physician’s specialty—psoriasis (yes/no), Physician’s workplace (yes/no), Physician’s experience with biologics (ordinal scale), Physician’s perspective of patient’s understanding of disease (ordinal scale) and treatment choice (ordinal scale), Physician GA severity (0–5 scale), and Treatment Satisfaction (0–10 scale). DLQI, Dermatology Life Quality Index; PGA, Physician Global Assessment; TSQM, Treatment Satisfaction Questionnaire for Medication; y, years.
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
MDPI and ACS Style
Okubo, Y.; Tang, A.C.; Inoue, S.; Torisu-Itakura, H.; Ohtsuki, M. Comparison of Treatment Goals between Users of Biological and Non-Biological Therapies for Treatment of Psoriasis in Japan. J. Clin. Med. 2021, 10, 5732. https://doi.org/10.3390/jcm10245732
AMA Style
Okubo Y, Tang AC, Inoue S, Torisu-Itakura H, Ohtsuki M. Comparison of Treatment Goals between Users of Biological and Non-Biological Therapies for Treatment of Psoriasis in Japan. Journal of Clinical Medicine. 2021; 10(24):5732. https://doi.org/10.3390/jcm10245732
Chicago/Turabian StyleOkubo, Yukari, Ann Chuo Tang, Sachie Inoue, Hitoe Torisu-Itakura, and Mamitaro Ohtsuki. 2021. "Comparison of Treatment Goals between Users of Biological and Non-Biological Therapies for Treatment of Psoriasis in Japan" Journal of Clinical Medicine 10, no. 24: 5732. https://doi.org/10.3390/jcm10245732
APA StyleOkubo, Y., Tang, A. C., Inoue, S., Torisu-Itakura, H., & Ohtsuki, M. (2021). Comparison of Treatment Goals between Users of Biological and Non-Biological Therapies for Treatment of Psoriasis in Japan. Journal of Clinical Medicine, 10(24), 5732. https://doi.org/10.3390/jcm10245732
Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.
