Patient preference for biologic treatments of psoriasis in Japan

Psoriasis is a chronic autoimmune disease affecting skin which may also manifest in nails and joints. Several biologic treatments have been approved in Japan for psoriasis. Each biologic has a different profile for efficacy and safety, including different dosing regimens and co‐payment considerations which may complicate treatment decisions made by patients and physicians during short consultations. Elucidating patient preference is expected to contribute to shared decision‐making between patients and physicians to optimize treatment satisfaction and outcomes. However, the number of studies investigating this in Japan is very limited. The study used a discrete choice experiment methodology to elicit patient preferences for hypothetical options in an experimental framework. Participants were asked to choose their preferred treatment option from two hypothetical choices, defined by different levels of six attributes (i.e. early onset of efficacy, long‐term efficacy, sustained efficacy after drug withdrawal, dosing convenience, co‐payment and risk of serious infection). The survey included 16 treatment choice scenarios and was completed by 395 participants. Across all participants, the attribute regarded as most important was sustained efficacy after drug withdrawal, followed by dosing convenience, co‐payment, long‐term efficacy, early onset of efficacy and risk of serious infection. The study found that patients prefer treatments which have durable efficacy and lower treatment burden characterized as fewer injection frequency and lower co‐payment. These results may be helpful to understand patient preference for biologic treatments used for psoriasis in Japan and contribute to shared decision‐making between patients and physicians to improve patient satisfaction and treatment outcomes.     

Retrospective analysis of systemic treatments for psoriasis patients attending a Psocare center in Florence. Relevance of biological drugs use and comorbidities

Background Psoriasis is a chronic inflammatory skin condition associated with several risk factors and comorbidities. Methods The present study outlines patient and therapy profiles emerging from the analysis of 471 patients affected by plaque psoriasis or psoriatic arthritis (PsA). Results In our sample, the age of onset and first diagnosis of PsA is significantly higher than plaque psoriasis and about 65% of the patients are either smoker or ex‐smokers, while 79% are not drinkers. We also report a different distribution in the use of systemic treatments compared to the Psocare report 2007, with a tendency for a larger use of biologics over classical systemic drugs and in particular etanercept is the main treatment for PsA, and efalizumab for plaque psoriasis. All biological treatments used in the study significantly reduced PASI score. The main comorbidity associated both with plaque psoriasis and with PsA was hypertension, while hyperlipidaemia was frequently present in patients under biologics treatment. Finally, a strong association between type II diabetes and PsA was also reported. Conclusions Current treatments have to consider general health conditions and patients habits. In this picture, biological drugs are emerging as the therapy of choice for their good efficacy in the long term management of psoriasis.     

Nail psoriasis: a retrospective study on the effectiveness of systemic treatments (classical and biological therapy)

Background Nail psoriasis represents a challenge for specialists. There is no comparative study of systemic treatment’s effectiveness at this site. Objective: Evaluate the response of nail psoriasis to classical and biological therapy and to compare the effectiveness and safety of the different treatments. Methods We performed a retrospective study of 84 patients with moderate–severe psoriasis seen at our Department between January 2006 and January 2009. Results Psoriasis was severe in 53.4%. In 75% of cases, the fingernails were affected, and the mixed form was the most frequently subtype. The mean baseline scores on the PASI and the NAPSI were 23.12 and 14.7 respectively; the correlation between the two scores fell at weeks 12 and 24 but had risen again at week 48. The baseline NAPSI score tended to be lower in women and significantly higher in patients over 65 years of age, family history of psoriasis, severe psoriasis and nail matrix involvement. In our series, 58.3% received classical treatment (acitretin, methotrexate, cyclosporin, PUVA, NUVB, REPUVA, RENUVB) and 41.7% received biological treatment (infliximab, efalizumab, etanercept, adalimumab).Significant reductions were found (P < 0.05) in the mean NAPSI scores at 12, 24 and 48 weeks with all the antipsoriatic agents except NUVB; significantly greater with cyclosporine (P < 0.01) and biological as infliximab and adalimumab at 12 and 24 weeks (differences between treatments disappeared at 48 weeks). Conclusion The response to treatment is slower in the nail lesions than in the skin lesions. The improvement of nail psoriasis is significant both with the classical treatments significantly higher in cyclosporin; and biological treatment (infliximab and adalimumab at 12 and 24 weeks).     

Biologic treatments for elderly patients with psoriasis

The number of elderly patients with psoriasis is increasing in Japan. However, biologic treatment is generally considered to be challenging in elderly patients, due to their increased risk of complications compared with younger patients. Our retrospective study aimed to evaluate the safety profile and efficacy of biologics in senior elderly patients (≥75 years old) with psoriasis. The study involved a cohort of 27 patients aged 75–88 years who were being treated with biologics over a period of more than 1 year. Initial biologics administrated to were adalimumab (five cases) and ustekinumab (22 cases). Eight patients discontinued treatment: two developed cancer; one was transferred to hospital; and five others experienced either bone fracture, interstitial pneumonia, cerebral hemorrhage resulting in death, decrepitude or developed hepatopathy following prophylactic tuberculosis treatment. Efficacy, evaluated by the percentage of patients achieving 75% reduction of Psoriasis Area and Severity Index score, was 76.9% at week 16 (n = 26), 88.0% at week 24 (n = 25) and 90.5% at week 52 (n = 21). Biologic treatments thus show clear efficacy in elderly patients with psoriasis, however, the increased frequency of adverse events requires rigorous patient observation.     

妊娠期银屑病治疗进展

银屑病是一种免疫相关的慢性炎症性疾病。大部分女性患者在育龄期发展为银屑病。目前,传统药物和生物制剂在治疗银屑病方面取得了良好的效果,但它们均有可能导致妊娠不良事件的发生。本综述旨在讨论用于治疗妊娠期银屑病的主要药物包括传统药物和生物制剂的疗效以及安全性,以及既往报道的妊娠期银屑病的治疗的研究,为临床决策提供参考。     

Clinical characteristics of Japanese pustular psoriasis: A multicenter observational study

Generalized pustular psoriasis (GPP) is a rare and severe subtype of psoriasis. Because of its rarity, GPP studies with a large sample size have been scarce. We studied the characteristics of GPP and pustular psoriasis using data from the West Japan Psoriasis Registry that had been registered until the end of December 2020. The dataset included 104 patients with pustular psoriasis and 1290 patients with other subtypes of psoriasis. Multivariate analysis revealed a significantly greater number of female patients, a significantly lower mean body mass index, and a significantly lower ratio of habitual drinkers in pustular psoriasis, compared to other subtypes of psoriasis. Of the 104 patients, 102 had GPP, including 88 von Zumbusch, 10 juvenile-onset, and four annular pustular psoriasis. Although the male : female ratio of GPP with psoriasis vulgaris (GPP+PsV) (47/20) was similar to that of psoriasis in Japan, the GPP without PsV (GPP?PsV) group highlighted a female predominance (13/22). The mean age at GPP onset was 45.3 years, and the mean interval from PsV onset to GPP onset was 12.5 years. Four of nine patients with GPP had an IL36RN gene mutation. Infection, medicine, and pregnancy were the precipitating factors for GPP. A family history of psoriasis was present in eight (7.8%) patients with GPP. Twenty-four patients with GPP had psoriatic arthritis. Biologics were used in 76.5% of patients with GPP, followed by etretinate (37.3%), cyclosporine (24.5%), methotrexate (13.7%), apremilast (8.8%), and granulocyte and monocyte adsorption apheresis (6.9%). Etretinate was used in 17 (51.5%) of 33 patients with GPP with less than 10-year history. Thus, etretinate remains a good treatment option for GPP even in the era of biologics. Hypertension was the most commonly identified comorbidity, followed by diabetes. We believe that the characteristics revealed in this study can further contribute to effective GPP management.     

脓疱型银屑病的生物制剂治疗

脓疱型银屑病是银屑病中比较严重、治疗困难、可危及患者生命的类型。目前治疗方法主要包括系统使用阿维A酸、环孢素和甲氨喋呤，以及光化学疗法和局部治疗。但一些患者对上述治疗效果不佳，最近国际上报道了一些生物制剂治疗脓疱型银屑病的临床研究。本文对这些研究进行了综述。     

Infliximab for severe, treatment-resistant psoriasis: a prospective, open-label study

BACKGROUND: Infliximab, a mouse-human chimeric monoclonal antibody directed against tumour necrosis factor-alpha, has been shown to be effective for moderate to severe psoriasis, but there are few data published on its use in recalcitrant, treatment-resistant disease or in combination with other antipsoriatic therapies. OBJECTIVES: To report our experience with infliximab in the treatment of patients attending a tertiary referral service with severe recalcitrant disease. METHODS: All patients attending a tertiary referral service for severe psoriasis who were treated with infliximab between 2002 and July 2005 were entered into a prospective, open-label study. Details on disease phenotype, clinical course and adverse events were recorded together with measures of disease severity [Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index, clinical photography] at baseline, weeks 2 and 6, and then at 2-monthly intervals throughout the treatment period. RESULTS: Twenty-three patients were treated with infliximab during the study; one patient had pustular psoriasis and was therefore excluded from statistical analysis. All had severe disease (baseline PASI 26.5+/-6.7, mean+/-SD, n=22) and had received at least two systemic therapies for psoriasis in the past; 16 were taking one or more concomitant therapies at the time of treatment initiation. At week 10, 95% had achieved a 50% or greater improvement in baseline PASI (PASI 50), and 77% had achieved a 75% or greater improvement (PASI 75). Efficacy was sustained in the longer term, with eight of 10 patients on treatment for more than 11 months maintaining at least a PASI 50. Only one patient had treatment withdrawn due to lack of efficacy, two suffered severe systemic infections including extrapulmonary tuberculosis (splenic abscess) and cellulitis, and six have discontinued due to adverse effects including infusion reactions (two), severe thrombocytopenia (one), hepatitis (one) and malignancy (two). CONCLUSIONS: Data from this open-label study suggest that infliximab is a rapidly effective treatment for patients with severe, treatment-resistant disease, although approximately 25% of patients had to discontinue therapy due to the development of serious adverse effects. Long-term follow-up, continued pharmacovigilance, and further controlled comparative studies will be required to evaluate fully the risks associated with infliximab in the context of this already difficult to treat population.     

Patient satisfaction and efficacy of calcipotriol plus betamethasone dipropionate gel in plaque psoriasis patients with poor adherence

Poor adherence to treatment makes achievement of expected therapeutic outcomes more difficult, especially in chronic disorders like psoriasis. There are several critical factors that affect adherence, including therapeutic efficacy, patient satisfaction, patient treatment preferences and ease of application, especially in topical therapy. The fixed combination of calcipotriol plus betamethasone dipropionate in a gel formulation (Cal/BDP gel) has been recommended as a first-line topical treatment for mild to moderate plaque. To examine whether Cal/BDP gel can effectively improve treatment adherence, we investigated the effects of once-daily Cal/BDP gel on factors affecting adherence at weeks 4, 8 and 12 in patients with plaque psoriasis who had poor adherence. A total of 46 subjects were enrolled and 41 subjects (26 men, 15 women; mean age, 50.5 years) were included in the analysis. The following items were evaluated: Patient Preference Questionnaire, nine-item Treatment Satisfaction Questionnaire for Medication, Physician’s Global Assessment (PGA), modified Psoriasis Area and Severity Index (m-PASI), body surface area (BSA), pruritus, medication adherence and application time. In patients with poor adherence, many preferred treatment with Cal/BDP gel and evaluated its convenience as “excellent” at weeks 4 and 12. At week 12, the proportion of “clear”/”very mild” ratings using PGA reached 20.5%, the change from baseline on m-PASI was −61.3% and the change from baseline on BSA was −39.8%, suggesting that the skin symptoms of psoriasis had improved greatly. In most patients, the longer they used Cal/BDP gel, the greater their preference and satisfaction and the higher the therapeutic effect, which increased markedly over 12 weeks. These results suggest that Cal/BDP gel can effectively improve treatment adherence. Conversely, high adherence to Cal/BDP gel must enhance the therapeutic effect. Therefore, we expect that Cal/BDP gel could become the mainstay of topical psoriasis treatment in patients with poor adherence.     

Efficacy and tolerability of biologic and nonbiologic systemic treatments for moderate-to-severe psoriasis: meta-analysis of randomized controlled trials

Background The comparative efficacy and tolerability of conventional and biologic treatments for moderate‐to‐severe plaque psoriasis are unknown. Objectives To perform a systematic review and meta‐analysis of randomized controlled trials (RCTs) reporting efficacy of systemic treatments approved for moderate‐to‐severe psoriasis by means of the Psoriasis Area and Severity Index (PASI). Methods We identified relevant articles by systematic electronic searches (Cochrane Library, Medline, Embase, Scopus). Efficacy was defined as proportion of participants with ≥ 75% decrease in PASI (PASI‐75) at primary efficacy measurement (week 8–16). PASI‐75 response rates of double‐blind placebo‐controlled trials were summarized as risk differences (RDs) and pooled using random effects models. Tolerability was assessed from rates of withdrawals and adverse events. Results Twenty‐four RCTs totalling 9384 patients were analysed qualitatively. Sixteen double‐blind placebo‐controlled trials were eligible for meta‐analysis. Infliximab was significantly superior to all other interventions [RD 77%, 95% confidence interval (CI) 72–81%]. Adalimumab (RD 64%, 95% CI 61–68%) was superior to ciclosporin (RD 33%, 95% CI 13–52%), efalizumab (RD 24%, 95% CI 19–30%), etanercept 50 mg twice weekly (RD 44%, 95% CI 40–48%) and etanercept 25 mg twice weekly (RD 30%, 95% CI 25–35%). Efalizumab was significantly less efficacious than fumaric acid esters (RD 48%, 95% CI 32–64%). Rates of withdrawals due to adverse events were highest for methotrexate and fumaric acid esters. Conclusions The efficacy of systemic agents approved for moderate‐to‐severe psoriasis differs considerably both within and between biologics and nonbiologics. Infliximab is most efficacious, followed by adalimumab. Patients receiving infliximab have an excess chance of 77% over placebo to achieve PASI‐75 response. Published evidence questions regulatory guidelines that recommend biologics as second‐line therapy for moderate‐to‐severe plaque psoriasis.     

Japanese guidance for use of biologics for psoriasis (the 2013 version)

The clinical use of adalimumab and infliximab, human anti‐tumor necrosis factor (TNF)‐α monoclonal antibodies, for psoriasis began in January 2010. In January 2011, ustekinumab, a human anti‐interleukin‐12/23p40 (IL‐12/23p40) monoclonal antibody, was newly approved as the third biologic with an indication for psoriasis. While all of these biologics are expected to exhibit excellent therapeutic effect for psoriasis and to contribute to the improvement of quality of life in patients, these drugs require careful safety measures to prevent adverse drug reactions, such as serious infections. The new guidance, an English version prepared by revising the Japanese Guidance/Safety Manual for Use of Biologics for Psoriasis 2011 (in Japanese), is intended to provide up‐to‐date, evidence‐based recommendations and safety measures on the use of biologics, and describes the optimal use of the three biologics, medical requirements for facilities for using biologics, details of safety measures against reactivation of tuberculosis and hepatitis B virus infection, and recommendable combination therapies with biologics.     

Economic evaluation of systemic therapies for moderate to severe psoriasis

Background New biologics have dramatically changed therapeutic options for psoriasis, albeit at additional cost. Objectives To determine the cost‐effectiveness and optimal treatment sequence for moderate to severe psoriasis. Methods Psoriasis Area and Severity Index (PASI) response rates from 22 randomized controlled trials evaluating biologic (adalimumab, efalizumab, etanercept, infliximab) and nonbiologic systemic (methotrexate, ciclosporin) agents were considered. Short‐term efficacy was based on relative probabilities of achieving PASI response (50/75/90) in a meta‐analysis of trials. Published evidence and assumptions were used to predict long‐term efficacy. Treatment benefits were determined by the relationship between PASI response and the EuroQOL 5D health utility measure. Costs included therapy, administration, monitoring and hospitalization. Incremental cost‐effectiveness ratios (ICERs) were calculated and treatments ranked relative to supportive care. Results Infliximab provided the most incremental quality‐adjusted life‐years (QALYs) vs. supportive care (0·18 QALYs; 95% confidence interval, CI 0·13–0·24), followed by adalimumab (0·16 QALYs; 95% CI 0·11–0·22). Methotrexate and ciclosporin were less beneficial (0·13 and 0·08 QALYs, respectively) but were cost saving and considered the first two treatments in the optimal sequence. Comparing biologics, adalimumab was most cost effective (ICER £30 000 per QALY), followed by etanercept (£37 000 per QALY), efalizumab (£40 000 per QALY) and infliximab (£42 000 per QALY). Conclusions Methotrexate and ciclosporin are cost effective but require monitoring for toxicities. Of the biologics, adalimumab was most cost effective following conventional systemic treatment failure or inadequate response. Payers and policymakers will have to decide how to utilize their budgets effectively for treating patients with moderate to severe psoriasis.     

Use of TNF‐inhibitors and ustekinumab for psoriasis during pregnancy: A patient series

From 2002 to 2016 a total of seven women with severe refractory psoriasis were exposed to the TNF‐inhibitors infliximab and adalimumab or to the IL12/23 inhibitor ustekinumab during one or more pregnancies. Maternal, fetal or teratogenic toxicity were not detected during pregnancy and puerperium. All pregnancies were uneventful and resulted in delivery of 10 healthy children in total, one of the women is due February 2017. Postpartum, five of the women were lactating, but none of the women or newborns developed adverse reactions. Data on safety of treatment during breastfeeding are sparse, but so far appears to be safe due to the lack of absorption across the gastrointestinal lining. Currently biological therapy with either TNF‐inhibitors or ustekinumab is not recommended during pregnancy, however in selected women with severe psoriasis these treatment modalities may be considered.