Predictors of time to relapse following ustekinumab withdrawal in patients with psoriasis who had responded to therapy: An 8-year multicenter study.

BACKGROUND: Data on predictors and time to relapse in patients with psoriasis who discontinue therapy in a real-world setting are scarce. OBJECTIVE: To investigate predictors of relapse after withdrawal of ustekinumab in patients with psoriasis. METHOD: This study screened 500 patients with psoriasis who received ustekinumab (669 treatment episodes) between 2011 and 2018. Overall, 202 patients (accounting for 304 treatment episodes) who had responded to therapy and were withdrawn from ustekinumab treatment were included. RESULTS: The cumulative probabilities of being relapse-free at 6, 12, 18, 24, and 36 months after withdrawal from ustekinumab treatment were 49.3%, 12.6%, 5.3%, 4.7%, and 1.6%, respectively. Multivariate regression analyses with a generalized estimating equation showed that after adjustments, biologic-naive status, maximum improvement in Psoriasis Area and Severity Index during ustekinumab treatment, time to achieve a 50% improvement in baseline Psoriasis Area and Severity Index score after initiation of ustekinumab, family history of psoriasis, chronic kidney disease, and immunosuppressant use while not taking ustekinumab were significant predictors of time to relapse following discontinuation of ustekinumab. LIMITATION: Nonrandomized allocation of duration of treatment and follow-up. CONCLUSION: Given the high rates of relapse, withdrawal of ustekinumab from patients with well-controlled psoriasis cannot be recommended.

Predictors of hepatitis B and C virus reactivation in patients with psoriasis treated with biologic agents: a 9-year multicenter cohort study.

BACKGROUND: The increasing use of biologics is accompanied by a risk of hepatitis B (HBV) and C virus (HCV) reactivation. OBJECTIVE: To determine the predictors of HBV and HCV reactivation in patients with psoriasis receiving biologics. METHODS: This study screened 2060 patients with psoriasis (3562 treatment episodes) who were taking biologics from 2009 to 2018. There were 359 patients with psoriasis with HBV (561 treatment episodes) and 61 with HCV infection (112 treatment episodes). RESULTS: During 8809 and 1522 person-months of follow-up, 88 treatment episodes for HBV involved HBV reactivation, and 14 episodes of HCV involved reactivation. The reactivation rate was significantly higher in treatment episodes of chronic HBV infection than in that of occult HBV (34.3% vs 3.2%, P = .001) and resolved HBV (34.3% vs 5.0%, P < .001). The multivariate analysis revealed that being hepatitis B surface antigen seropositive, being hepatitis B e-antigen seropositive, and tumor necrosis factor-α-inhibitor therapy were risk factors for HBV reactivation, whereas antiviral prophylaxis was effective in reducing the risk of HBV reactivation. No predictors were significantly associated with HCV reactivation. LIMITATIONS: Observational design and a lack of a comparison group. CONCLUSION: Patients with psoriasis on biologics have a risk of HBV and HCV reactivations, particularly those who are seropositive for hepatitis B surface antigen and hepatitis B e-antigen and undergoing tumor necrosis factor-α-inhibitor therapy.

Recommendations for psoriatic arthritis management: A joint position paper of the Taiwan Rheumatology Association and the Taiwanese Association for Psoriasis and Skin Immunology.

In Taiwan, the incidence and prevalence of psoriatic arthritis (PsA) have risen significantly in recent years. Moreover, data from the Taiwan National Health Insurance Research Database (NHIRD) show that more than 85% of PsA patients are treated with just non-steroidal anti-inflammatory drugs (NSAIDs) and/or conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). Taiwanese clinicians have also expressed concerns regarding uncertainties in the diagnosis of PsA and the delayed, interrupted, and/or tapered use of biologics, as well as differences in therapeutic preferences between and within dermatologists and rheumatologists. To address these issues, the Taiwan Rheumatology Association and the Taiwanese Association for Psoriasis and Skin Immunology jointly convened a committee of 28 clinicians from the fields of rheumatology, dermatology, orthopedics, and rehabilitation, to develop evidence-based consensus recommendations for the practical management of PsA in Taiwan. A total of six overarching principles and 13 recommendations were developed and approved, as well as a treatment algorithm with four separate tracks for axial PsA, peripheral PsA, enthesitis, and dactylitis. Psoriasis (PsO) management was not discussed here, as the Taiwanese Dermatological Association has recently published a comprehensive consensus statement on the management of PsO. Together, these recommendations provide an up-to-date, evidence-based framework for PsA care in Taiwan.

Biologics switch in psoriasis.

Aim: No guidelines exist for biologic switch in psoriasis after treatment failure. Although, switching between TNF-α antagonists has been reviewed, switching information about newer biologics is limited. Materials & methods: We did a thorough systematic review from 'PubMed' and 'Embase', which includes new biologics such as IL-12/IL-23 antagonists, IL-17A antagonists and IL-23 antagonists. Results & conclusion: New biologics such as IL-17 antagonist or IL-23 antagonist show greater responses in bio-experienced patients and could even be used for patients in whom previous treatments failed.

Human leukocyte antigen and demographic characteristics in Chinese patients with active peripheral type psoriatic arthritis who had inadequate response to conventional disease-modifying antirheumatic drugs in a single dermatologic clinic.

BACKGROUND: Correlation between severity of psoriasis and psoriatic arthritis (PsA) is inconsistent. Also, human leukocyte antigen (HLA)-Cw6 was found to be underrepresented in severe psoriasis who failed conventional systemic therapies, but the effect of HLA polymorphism on PsA severity needs to be confirmed. OBJECTIVES: To describe the severity of psoriasis, demographic features and HLA polymorphism among Chinese patients with active peripheral type PsA who had inadequate response to conventional disease-modifying antirheumatic drugs. METHODS: We included all patients with PsA who had at least 3 tender and swollen peripheral joints despite at least two conventional non-biologic treatments in our clinic. Demographic results were compared with global pivotal studies of biologics for PsA. HLA-Cw and HLA-DRB1 genotyping was also analyzed. RESULTS: We identified 60 patients who met our inclusion criteria. The male to female ratio was 1.31:1. The majority of patients presented with psoriasis first (81.7%). The mean interval between psoriasis and PsA was 7.2 ± 8.1 years (mean ± SD). The baseline number of tender and swollen joints was 14.9 ± 10.7 and 11.3 ±10.2, respectively. In total, 41.7% subjects had more than 3% body surface area involvement of psoriasis. Genotyping of HLA-Cw and HLA-DRB1 was performed in 47 subjects. HLA-Cw*0702 was the most frequent allele (29.8%), followed by HLA-Cw*01 (26.6%). The frequency of HLA-Cw*0602 allele was similar to normal population. The most frequent HLA-DRB1 allele was HLA-DRB1*04 (20.2%), followed by HLA-DRB1*08 (16.0%). No cases carrying HLA-DRB1*13 were detected. CONCLUSIONS: Compared with Western population, our patients had less psoriasis and PsA burden. The frequencies of HLA-Cw*06, HLA-Cw*12, and HLA-DRB1*07 were not increased. In contrast, HLA-Cw*0702 and HLA-DRB1*08 allele frequencies were increased compared with psoriasis patients and normal population in Taiwan. Future studies are still needed to characterize the demographic and genetic features of high need PsA patients.

Safety Profile of Secukinumab in Treatment of Patients with Psoriasis and Concurrent Hepatitis B or C: A Multicentric Prospective Cohort Study.

Safety data for secukinumab in patients with psoriasis and viral hepatitis are lacking. The aim of this study is to investigate the risk of reactivation of hepatitis B virus (HBV)/hepatitis C virus (HCV) in patients with psoriasis who are receiving secukinumab therapy. This multicentre study screened 284 patients with psoriasis with available HBV and HCV serological data and 63 patients with concurrent HBV/HCV infection were enrolled. In the absence of antiviral prophylaxis, 7 of 46 (15.2%) patients with HBV exhibited HBV reactivation during secukinumab therapy. The risk of reactivation was significantly higher in HBsAg-positive patients, compared with HBsAg-negative/HBcAb-positive patients (24.0% vs. 4.17%, p = 0.047). One of 14 (7.1%) HCV patients showed enhanced replication of HCV with hepatitis. No virus reactivation occurred in patients receiving antiviral prophylaxis. HBsAg-positive and HBsAg-negative/HBcAb-positive psoriasis patients can develop virus reactivation during secukinumab therapy, thus necessitating close monitoring of viral load and considering an antiviral prophylaxis for all HBsAg-positive patients with psoriasis.

Tofacitinib in psoriatic arthritis.

Psoriatic arthritis is a heterogeneous disease that has been difficult to manage until the recent advent of biologics. However, there are still unmet medical needs for newer agents. Tofacitinib is a Janus family of kinases inhibitor approved for treating rheumatoid arthritis in many countries and psoriasis in Russia. We reviewed the evidences of tofacitinib in psoriatic arthritis treatment. The efficacy and safety profiles result from Phase III clinical trials (OPAL BROADEN and OPAL BEYOND) and one open-label extension study (OPAL BALANCE). Both tofacitinib 5 or 10 mg twice a day were superior to placebo for American College of Rheumatology 20% improvement criteria response at 3 months and showed significant improvement of skin, enthesitis and dactylitis. Tofacitinib is a promising treatment option for psoriatic arthritis.

Serial QuantiFERON-TB Gold testing in patients with psoriasis treated with ustekinumab.

BACKGROUND: There is increasing concern about the risk of latent tuberculosis infection (LTBI) reactivation during the use of biologics for psoriasis. Although ustekinumab had been documented with low risk of tuberculosis, the long-term follow-up of LTBI as determined by QuantiFERON-TB Gold (QFT-G) testing in patients treated with ustekinumab is limited. OBJECTIVES: This study aims to use serial QFT-G testing as a screening method for detecting LTBI in patients with psoriasis from an intermediate tuberculosis burden country. METHODS: This retrospective review investigated 134 psoriatic patients in whom ustekinumab was prescribed for at least one year between 2010 and 2016 in National Taiwan University Hospital. All patients underwent annular QFT-G testing during ustekinumab therapy. RESULTS: Among the 134 enrolled patients, baseline LTBI rate was 13.4% (18/134). Indeterminate QFT-G result was noted in 5.2% (7/134) of patients and 71.4% (5/7) of them turn to be QFT-G negative during the next testing. 81.3% (109/134) of patients had a negative QFT-G at baseline and the seroconversion rate was 7.3% (8/109) in the serial QFT-G. All the patients in the conversion group were referred to a pulmonologist for evaluation and 81.5% (22/27) of them underwent chemoprophylactic therapy while on ustekinumab. No active TB infection was noted during further follow-up with or without chemoprophylaxis. CONCLUSIONS: This study revealed that psoriatic patients receiving long-term ustekinumab therapy had a low QFT-G conversion rate (7.3%). The clinical significance of QFT-G conversion remains controversial and needs larger scale trials to investigate.

Managing Scalp Psoriasis: An Evidence-Based Review.

BACKGROUND: Scalp psoriasis is commonly the initial presentation of psoriasis, and almost 80 % of patients with psoriasis will eventually experience it. OBJECTIVE: Although several systematic reviews and guidelines exist, an up-to-date evidence-based review including more recent progress on the use of biologics and new oral small molecules was timely. METHODS: Of the 475 studies initially retrieved from PubMed and the 845 from Embase (up to May 2016), this review includes 27 clinical trials, four papers reporting pooled analyses of other clinical trials, ten open-label trials, one case series, and two case reports after excluding non-English literature. RESULTS: To our knowledge, few randomized controlled trials (RCTs) are conducted specifically in scalp psoriasis. Topical corticosteroids provide good effects and are usually recommended as first-line treatment. Calcipotriol-betamethasone dipropionate is well tolerated and more effective than either of its individual components. Localized phototherapy is better than generalized phototherapy on hair-bearing areas. Methotrexate, cyclosporine, fumaric acid esters, and acitretin are well-recognized agents in the treatment of psoriasis, but we found no published RCTs evaluating these agents specifically in scalp psoriasis. Biologics and new small-molecule agents show excellent effects on scalp psoriasis, but the high cost of these treatments mean they may be limited to use in extensive scalp psoriasis. CONCLUSIONS: More controlled studies are needed for an evidence-based approach to scalp psoriasis.

Epidemiology of psoriatic disease and current treatment patterns from 2003 to 2013: A nationwide, population-based observational study in Taiwan.

BACKGROUND: Recent global data show an increasing prevalence of psoriasis and psoriatic arthritis in western countries. OBJECTIVE: The current study analyzed the trend of prevalence rates of psoriasis and psoriatic arthritis in Taiwan and examined biologic prescription patterns by different specialties. METHODS: Data were accessed from the national payer National Health Insurance Research Database in Taiwan. This study protocol was approved by Joint Institutional Review Board established by Medical Research Ethics Foundation (No 13-S-001). RESULTS: Between 2003 and 2013, the prevalence of psoriasis and psoriatic arthritis increased by 41% (from 15.54 to 21.90 per 10,000 population) and 191% (from 0.45 to 1.31 per 10,000 population), respectively, while the prevalence of psoriatic arthritis among patients with psoriatic disease increased from 6.3% to 12.7%. Dermatologists are the main caregivers for patients with psoriasis and psoriatic arthritis; however, data suggest a decreasing trend in the proportion of dermatologists for psoriasis patients from 24.7% between 2003 and 2008 to 10.74% between 2008 and 2013, with a corresponding decrease in dermatologists for psoriatic arthritis patients from 62.30% to 44.65% during the same periods, respectively. In 2013, of the 51,191 patients with psoriasis, only 596 (1.16%) received biologics (73.3% by dermatologists and 25.8% by rheumatologists), while 1120 of the 7470 (14.99%) psoriatic arthritis patients received biologics (72.8% by rheumatologists and 22.3% by dermatologists). The proportion of biologics use was 1.12% and 7.75% among all patients with only psoriasis and 8.01% and 26.70% among all patients with psoriatic arthritis seen by dermatologists and rheumatologists, respectively. CONCLUSION: The prevalence of psoriasis and psoriatic arthritis is increasing in Taiwan. The use of biologics in patients with psoriatic arthritis was comparable to that reported in previous studies in the United States and Europe; however, the use of biologics remained low in patients with psoriasis in Taiwan.

Concomitant Sleep Disorders Significantly Increase the Risk of Cardiovascular Disease in Patients with Psoriasis.

BACKGROUND: The increased rates of cardiovascular morbidity and mortality in patients with psoriasis are not adequately explained by traditional risk factors. Whether concomitant sleep disorders (SDs) modify the risk of cardiovascular disease (CVD) in patients with psoriasis remains unknown. METHODS: Using the Taiwan National Health Insurance Research Database (NHIRD), we conducted a cohort study to investigate the association between concomitant SDs and CVD risk in patients with psoriasis. Data from 99,628 adults who received a psoriasis diagnosis during the period from 2004 to 2010 were analyzed. Cox proportional hazards regression analysis models were used to compare the risks of ischemic heart disease (IHD) and stroke between patients with and without SDs. RESULTS: Psoriasis patients with a concomitant SD had significantly higher risks of IHD (adjusted hazard ratio [aHR], 1.25; 95% confidence interval [CI], 1.22-1.28) and stroke (aHR, 1.24; 95% CI, 1.16-1.33) as compared with psoriasis patients without SDs. All psoriasis patient subgroups, including those with mild and severe psoriasis and those with and without arthritis, had increased HRs for IHD and stroke. The increases in IHD and stroke risks conferred by SDs were proportional to the dose of hypnotics used. The effect of SDs on the risks of IHD and stroke was greater in young adults than in middle-aged and older adults. CONCLUSIONS: The risks of IHD and stroke were higher for psoriasis patients with SDs than for those without SDs. Clinicians should carefully evaluate CVD risk, particularly in young patients with psoriasis.

Correlation of IL36RN mutation with different clinical features of pustular psoriasis in Chinese patients.

Different studies have reported various values for the percentage of patients with IL36RN mutations, and it has also been reported that the sites of these mutations differ among different ethnicities. The current study was a cross-sectional study conducted to investigate the risk factors predicting IL36RN mutation in Chinese patients with different clinical features of pustular psoriasis. 57 Han Chinese patients, including 32 with generalized pustular psoriasis, 14 with palmoplantar pustulosis, 9 with plaque-type psoriasis with pustules, and 2 with erythrodermic psoriasis, were enrolled between March 2013 and July 2014. Blood samples were collected, genomic DNA was extracted from leukocytes, and polymerase chain reaction (PCR)-based Sanger sequencing was used to analyze the coding exons and flanking introns of the IL36RN gene. The patients with generalized pustular psoriasis exhibited the highest IL36RN mutation rate (75 %) among the aforementioned patient types, with the subgroup consisting of those patients who had features of acrodermatitis continua of Hallopeau exhibiting the highest c.115+6T>C mutation rate (93.8 %). In addition, early onset, ever generalized pustular psoriasis (more than two attacks), ever acrodermatitis continua of Hallopeau, inverse psoriasis, and a family history of pustular psoriasis were associated with IL36RN mutation. The c.115+6T>C mutation was the most common and the most important variant in all subtypes of pustular psoriasis with IL36RN mutations among our sample of Chinese patients.

Risk Factor Analysis for the Immunogenicity of Adalimumab Associated with Decreased Clinical Response in Chinese Patients with Psoriasis.

Although anti-drug antibodies against biologics have been associated with decreased clinical efficacy, the immunogenicity of biologics seems to vary between drugs, diseases and ethnicities. This study aims to investigate the predictors for the formation of anti-adalimumab antibodies (AAA) and the clinical consequences of AAA formation. In 53 Chinese psoriatic patients treated with adalimumab, AAA was detected in 50.9%. Differences in Psoriasis Area and Severity Index 75 (PASI75) response rates among patients with and without AAA were significant (44.4% vs. 88.5%; p = 0.001). Patients with AAA had significantly lower trough concentrations of adalimumab than those without AAA. Risk factor analysis showed that treatment interruption, low trough adalimumab concentration, absence of concomitant methotrexate use and biologics switching were associated with a higher AAA titre. The treatment pattern of biologics influences the risk of AAA formation, thereby leading to reduced efficacy of adalimumab.

Cutaneous irritancy of water.

Abstract Water is an ubiquitous irritant that exerts its irritancy through different mechanisms. Water passage and optimal water content is a highly controlled process of human skin and changes in the water gradient may lead to skin diseases. The pH, osmolarity, and temperature of water can all be attributes of water irritancy. In addition, the irritancy of water is also determined by individual susceptibility.

Etanercept use for psoriasis in Taiwan: a case series study.

BACKGROUND: The reported efficacy and safety of some biologic agents for psoriasis vary between Caucasians and Asians. Few reports of etanercept exist in psoriasis patients within the Asia-Pacific region. OBJECTIVES: The study aims to report our clinical experience of etanercept in the treatment of patients with moderate-to-severe psoriasis in Taiwan. METHODS: A retrospective analysis of 59 patients with moderate-to-severe psoriasis who received etanercept was conducted in a tertiary referral center. RESULTS: Etanercept therapy resulted in a reduction of mean Psoriasis Area and Severity Index (PASI) of 47% at week 12 and 61% at week 24. After 12 weeks of treatment, 48%, 26%, and 3.4% of the patients achieved at least PASI50, 75 and 90 response, respectively. At week 24, the proportion of patients achieving at least PASI50, 75 and 90 response was 59%, 37%, and 14%, respectively. Etanercept efficacy in achieving PASI75 improvement was, however, lower than that reported in previous pivotal placebo-controlled trials. No cases of active tuberculosis, viral hepatitis or malignancies were observed during the observation period. CONCLUSION: Our case series demonstrated the efficacy and safety of etanercept for the management of moderate-to-severe psoriasis in Taiwan.

Intralesional therapy for psoriasis.

Localized resistant plaques of psoriasis often remain despite highly effective anti-psoriasis treatment. Intralesional therapy is often used to treat various malignant, infectious or inflammatory cutaneous diseases, including psoriasis. Despite the presence of many review articles on the treatment of psoriasis, no articles exist which review the use of intralesional therapy for psoriasis. In this article, we review the published literatures of intralesional therapy for psoriasis. Corticosteroids, methotrexate, cyclosporin, biologics, botulinum toxin type-A, 15-hydroxyeicosatetraenoic acid, and chemotherapy agents such as 5-fluorouracil are discussed. Also, agents which may be used intralesionally and have the potential to treat psoriasis will also be reviewed such as bleomycin, vincristine or vinblastine, mitomycin-C, aminophylline, 5-aminolevulinic acid, rituximab, bevacizumab and pentoxifylline are included.

Epidemiology and comorbidities of psoriasis patients in a national database in Taiwan.

BACKGROUND: Recent findings in psoriasis research have shown that psoriasis is frequently associated with systemic comorbidities. OBJECTIVES: This study aims to describe the epidemiology of psoriasis and the prevalence of comorbidities in patients with psoriasis in Taiwan. METHODS: Patients who had at least one outpatient visit or admission with ICD-9-CM diagnosis code 696.0-1 in the Taiwan National Health Insurance (NHI) claims database during 2006 were identified as psoriasis cases. The cases were further classified into moderate to severe psoriasis (sPsO) for those who had previously received systemic therapy during the study period and mild psoriasis (mPsO) for those who had not. The cases were matched in a 1:4 ratio with controls from a sample cohort of 997,771 enrolees representative of the Taiwan population. Matching variables included age, gender and residential area. Prevalence of comorbidities was assessed using prevalence relative risk (RR) based upon a Cox proportional regression model. RESULTS: 51,800 psoriasis cases were identified (prevalence=0.235%; mean age=46.4±18.6; male:female=1.6:1) and 17.5% of cases were sPsO type. Psoriasis was associated with a significantly increased prevalence ratio (RR; [95% confidence interval]) for hypertension (1.51; [1.47, 1.56]), diabetes (1.64; [1.58, 1.70]), hyperglyceridaemia (1.61; [1.54, 1.68]), heart disease (1.32; [1.26, 1.37]), hepatitis B viral infection (1.73; [1.47, 2.04]), hepatitis C viral infection (2.02; [1.67, 2.44]), rheumatoid arthritis (3.02; [2.68, 3.41]), systemic lupus erythematosus (6.16; [4.70, 8.09]), vitiligo (5.94; [3.79, 9.31]), pemphigoid (14.75; [5.00, 43.50]), pemphigus (41.81; [12.41, 140.90]), alopecia areata (4.71; [2.98, 7.45]), lip, oral cavity and pharynx cancer (1.49; [1.22, 1.80]), digestive organs and peritoneum cancer (1.57; [1.41, 1.74]), depression (1.50; [1.39, 1.61]), fatty liver (2.27; [1.90, 2.71]), chronic airways obstruction (1.47; [1.34, 1.61]), sleep disorder (3.89; [2.26, 6.71]), asthma (1.29; [1.18, 1.40]), and allergic rhinitis (1.25; [1.18, 1.33]). Conversely, psoriasis was not associated with an increased risk of Crohn's disease. CONCLUSIONS: Psoriasis was associated with a significantly increased risk of comorbidities, especially for those patients with moderate to severe disease. These health associations should be taken into consideration when evaluating the burdens of psoriasis and designing effective treatment plans.