Guselkumab: A Review in Moderate to Severe Plaque Psoriasis

Guselkumab (Tremfya^®) is a human immunoglobulin G1 λ (IgG1λ) monoclonal antibody (mAb) that blocks the interleukin-23 (IL-23)-mediated signalling pathway and is the first in its class to be approved in adults with moderate to severe plaque psoriasis in several countries, including the USA and EU. In the VOYAGE trials, guselkumab was superior to placebo and to adalimumab at week 16 in terms of the proportion of patients achieving an Investigator Global Assessment (IGA) score of 0/1 and ≥ 90% improvement from baseline in Psoriasis Area and Severity index score (PASI 90 response), with benefits of guselkumab over adalimumab maintained at week 24. To date, the beneficial effects of guselkumab treatment in these trials were maintained for up to 2 years. Inadequate responders to ustekinumab who were then randomized to guselkumab in NAVIGATE showed better responses than those randomized to ustekinumab between weeks 28–40, with a significantly greater mean number of visits at which patients had IGA 0/1 and ≥ 2-grade improvement in IGA score, as well as higher proportions of patients achieving PASI 90 and PASI 100 at week 52. Treatment with guselkumab improved health-related quality of life (HR-QOL) and patient-reported outcomes in all trials and was generally well tolerated. Guselkumab, administered by subcutaneous injection, is a useful new option for patients with moderate to severe plaque psoriasis.     

Clinical Efficacy of Efalizumab in Patients With Chronic Plaque Psoriasis: Results From Three Randomized Placebo-Controlled Phase III Trials: Part I

Background

Effective psoriasis therapies are needed for long-term symptom control.

Objective

Assess efalizumab (Raptiva®) efficacy in a large cohort of psoriasis patients.

Methods

Data from three Phase III, randomized, double-blind, parallel-group, placebo-controlled, multicenter studies were pooled. Patients (n = 1,651) with moderate to severe plaque psoriasis received 12 weeks of subcutaneous efalizumab 1 or 2 mg/kg/wk or placebo.

Results

All efficacy measures reached statistical significance within each of the individual studies (p < 0.001) and overall. More efalizumab-treated patients achieved ≥ 75% and ≥ 50% Psoriasis Area and Severity Index (PASI) improvement at week 12 than did placebo-treated patients (27.8% vs 3.8% [p < 0.001] and 56.1% vs 14.6% [p < 0.001], respectively). Significant PASI improvements occurred as early as week 2 (12.5% vs 7.9%, p =0.0001). Adverse events were generally mild to moderate.

Conclusion

Efalizumab resulted in early and significant improvement for all efficacy endpoints and was well tolerated in patients with moderate to severe chronic plaque psoriasis.     

Which Areas Are Still Left in Biologics Responsive Korean Patients with Moderate to Severe Plaque Psoriasis

BackgroundPsoriasis localized to certain body areas, such as the scalp, nails, palms, soles, intertriginous regions, and genital regions, is reportedly difficult to treat.ObjectiveTo investigate the biologics-resistant areas in South Korean patients with psoriasis treated with biologics.MethodsThe study included 50 patients with chronic moderate to severe plaque psoriasis from the Pusan National University Hospital and Chosun University Hospital between October 2019 and September 2020. The patients had at least one psoriatic lesion, were treated with biologics for more than six months, and exhibited a partial or good response (reaching a Psoriasis Area and Severity Index [PASI] score of 1~5 after biologics treatment).ResultsA total of 50 patients with psoriasis (32 male, mean±standard deviation 47.8±11 years), with a median PASI score of 1.8, were included. The most common biologics-resistant areas were the anterior lower leg (56.0%), followed by the knee (48.0%) and posterior lower leg (42.0%). The proportion of biologics-resistant areas were obtained for body regions traditionally considered as difficult-to-treat entities, including the fingernails (10.0%), toenails (14.0%), scalp (38.0%), palm (12.0%), sole (14.0%), and genital areas (10.0%).ConclusionThis study determined the biologics-resistant areas in South Korean patients, successfully treated with biologics, in a real-world clinical setting.     

Efficacy and Safety of Adalimumab among Patients with Moderate to Severe Psoriasis with Co-Morbidities

Background: Psoriasis is associated with a variety of major physical and mental co-morbidities. Objective: To assess the incremental burden of co-morbidities on patient-reported outcomes and evaluate the efficacy and safety of adalimumab in psoriasis patients with co-morbidities. Study Design: Data were obtained from the initial 16-week, double-blind treatment period of REVEAL (Randomized controlled EValuation of adalimumab Every other week dosing in moderate to severe psoriasis triAL), a randomized, multicenter, phase III clinical trial. Intervention: Patients with moderate to severe psoriasis were randomized in a 2 : 1 ratio to receive adalimumab 80 mg (two 40 mg injections administered subcutaneously) at baseline followed by one 40 mg injection every other week from week 1 to week 15 or placebo. Main Outcome Measures: Clinical severity (Psoriasis Area and Severity Index [PASI]) and patient-reported outcomes (Dermatology Life Quality Index [DLQI], Short Form 36 [SF-36] health survey, Work Productivity and Activity Impairment [WPAI] questionnaire) were assessed during the trial. The effect of selected co-morbidities (i.e. hypertension, psoriatic arthritis, hyperlipidemia, obesity, depression, other forms of arthritis, diabetes mellitus, and other cardiovascular diseases) on patient-reported outcomes was evaluated using multivariate analysis of covariance models. Subgroup analyses were performed by co-morbidity type to statistically compare the clinical efficacy, patient-reported outcome benefits, and safety of adalimumab with placebo in the presence of these conditions. Results: Study co-morbidities were each independently associated with significantly greater impairment on at least one general patient-reported outcome measured at baseline (all p < 0.05), with the exception of hyperlipidemia. During the 16-week study, adalimumab patients demonstrated significantly greater PASI 75 response rates (defined as a reduction of at least 75% in PASI scores from baseline) compared with placebo patients for all co-morbidity subgroups. Adalimumab provided consistent improvements in DLQI, SF-36 Physical Component Summary and Mental Component Summary scores, and WPAI total scores from baseline to week 16 within co-morbidity subgroups. Rates of serious adverse events (AEs), serious infectious AEs, and AEs leading to discontinuation were comparable between adalimumab and placebo for patients with co-morbidities. Conclusions: Co-morbidities were associated with additionally impaired health-related quality of life and work productivity in patients with psoriasis. Adalimumab significantly improved efficacy and patient-reported outcomes and was well tolerated in patients with co-morbidities.     

Spotlight on Ustekinumab in Moderate To Severe Plaque Psoriasis

Ustekinumab (Stelara?) is a human monoclonal antibody that binds to the p40 subunit common to both interleukin (IL)-12 and IL-23. It is indicated in the US for use in adult patients with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy. In the EU, it is indicated for those who failed to respond to, have a contraindication to, or are intolerant of other systemic therapies or phototherapy. In well designed, randomized clinical trials, regimens of subcutaneous ustekinumab 45 or 90?mg provided a rapid and durable improvement in Psoriasis Area and Severity Index scores for patients with moderate to severe plaque psoriasis. Treatment with ustekinumab 45 or 90?mg also improved health-related quality-of-life scores from baseline. More limited data indicate that ustekinumab also improves the symptoms of arthritis in patients with plaque psoriasis and psoriatic arthritis. Subcutaneous ustekinumab was generally well tolerated in clinical trials; most adverse events were mild in intensity and did not require dosage adjustment. A pooled analysis of clinical trial data indicated no specific patterns of infection for recipients of ustekinumab and that infection rates remained stable following cumulative exposure to the agent. Thus, subcutaneous ustekinumab provides an effective and well tolerated alternative for the symptomatic treatment of patients with moderate to severe plaque psoriasis.     

The Long-Term Safety of Adalimumab Treatment in Moderate to Severe Psoriasis

Background: A favorable benefit-risk profile has been established for adalimumab, with up to 5 years of treatment in 13 clinical trials in patients with moderate to severe chronic plaque psoriasis. Objective: The aim of this analysis was to assess the long-term safety of all adalimumab exposure in all psoriasis clinical trials. Methods: A total of six sets of data were analyzed as follows: (i) all cumulative safety data from all exposure for all adalimumab-treated patients in the 13 clinical trials in moderate to severe psoriasis (All Adalimumab Treatment Population) through April 2007, November 2008, and November 2009, respectively; (ii) longitudinal data for 1403 patients treated with adalimumab 40mg every other week (eow) dosing (Every Other Week Population) through June 2007 and April 2010; and (iii) data from placebo-controlled periods of clinical trials. Adverse events that occurred up to 70 days after the final dose of adalimumab were analyzed. Results: During placebo-controlled periods, a total of 572 patients had 173.0 patient-years (PYs) of exposure to placebo and 1188 patients had 370.5 PYs of exposure to adalimumab. Adverse event incidence rates, expressed as events per 100 PYs (events/100 PYs), for placebo- and adalimumab-treated patients for serious adverse events were 7.52 and 8.64, and for serious infectious adverse events were 2.89 and 2.43, respectively. In the 2007, 2008, and 2009 All Adalimumab Treatment Population there were, respectively, 1819 patients (2424.7 PYs), 2197 patients (4351.9 PYs), and 3010 patients (4844.7 PYs), with serious adverse event incidence rates of 6.51, 7.22, and 8.36 events/100 PYs, and serious infectious adverse event rates of 1.32, 1.38, and 1.65 events/100 PYs. In the 2007 and 2010 Every Other Week Population (n = 1403), there were 1883.5 and 2854.1 total PYs of exposure, respectively, with serious adverse event incidence rates of 6.32 and 6.87 events/100 PYs, and serious infectious adverse event rates of 1.33 and 1.37 events/100 PYs, respectively. Conclusions: Multiple lines of evidence from a total of six sets of safety data, with treatment for up to 5 years, including results from all adalimumab-treated patients, and a subset of patients treated with 40mg eow dosing, did not show evidence of cumulative toxicity, and showed adverse event rates that were generally stable or decreased with increased mean per-patient exposure.     

Alefacept Is Well Tolerated in Patients with Chronic Plaque Psoriasis

Traditional systemic treatments for moderate to severe chronic plaque psoriasis are often poorly tolerated and are associated with safety concerns that restrict their long-term use. Alefacept is a fully human fusion protein that selectively targets memory T cells, and it is expected to provide enhanced safety over traditional nonselective agents. The safety and tolerability profile of alefacept is reviewed using data from the clinical development program. The most common adverse events were similar among alefacept and placebo groups. As expected from its mechanism of action, alefacept reduced the number of CD4⁺ and CD8⁺ T cells, with selectivity for the memory subsets. This reduction was not associated with an increase in the incidence of infections. Alefacept was not immunogenic. Patients have received up to 6 courses of alefacept therapy and the safety and tolerability profile over multiple courses is similar to that of a single course. Alefacept offers hope for a safer means to provide long-term management of psoriasis.     

Efalizumab Therapy for Psoriasis in Patients with Inadequate Responses to Etanercept

Efalizumab is a recombinant humanized monoclonal antibody approved for the treatment of adult patients with moderate-to-severe chronic plaque psoriasis. We present six cases of favorable response to efalizumab therapy in patients with psoriasis who demonstrated inadequate response or who were nonresponders to treatment with etanercept, a tumor necrosis factor-α-binding fusion protein. The subsequent response of these patients suggests that efalizumab may be a viable treatment option for patients with psoriasis who respond poorly to etanercept.     

阿维A对中、重度斑块状银屑病患者Th17细胞相关因子的影响

目的探讨阿维A治疗中、重度斑块状银屑病的疗效以及对银屑病患者血清Th17细胞相关因子IL-17,IL-22及IL-23的影响,进一步阐明阿维A治疗寻常性银屑病的作用机制。方法 35例中、重度斑块状银屑病患者口服阿维A治疗8周,以银屑病皮损面积和严重程度(PASI)评分评价疗效;采用ELISA法检测健康对照组以及银屑病治疗组使用阿维A治疗前后血清IL-17,IL-22及IL-23的水平。结果阿维A治疗前后PASI评分明显下降(P<0.01);银屑病组和健康对照组比较,IL-17,IL-22和IL-23的血清水平均明显增高(P<0.01);阿维A治疗后血清中IL-17的水平(45.38±11.69)pg/mL,IL-22的水平(61.48±18.76)pg/mL及IL-23的水平(139.65±40.28 pg/mL),较治疗前显著下降(P均<0.01)。结论银屑病患者的血清中存在高水平的IL-17,IL-22和IL-23;阿维A治疗中、重度银屑病疗效明显,治疗后血清中IL-17,IL-22和IL-23明显降低;阿维A可能通过影响Th17细胞相关因子来发挥治疗银屑病的作用。     

英夫利昔单抗治疗中、重度斑块状银屑病系统评价

目的系统评价英夫利昔单抗治疗中重度斑块状银屑病的疗效和安全性。方法检索MEDLINE、Cochrane图书馆、EMBASE、ISI、CNKI、CBM和VIP,收集所有关于英夫利昔单抗治疗银屑病的随机对照试验。根据纳入与排除标准筛选文献、评价质量、提取资料,采用RevMan5.0软件进行Meta分析。结果共纳入5个随机对照试验,包括1 549例患者。Meta分析结果显示:静滴英夫利昔单抗能显著提高达到PASI 75的例数(P<0.001);静滴英夫利昔单抗与安慰剂组比较,在1个或多个不良反应的发生率方面有统计学意义(P<0.001),而在严重不良反应的发生率方面无统计学意义(P=0.22)。结论现有证据表明,静滴英夫利昔单抗对中重度斑块状银屑病具有良好的疗效和较好的耐受性。     

阿维A治疗中重度银屑病30例临床分析

目的观察阿维A治疗中重度银屑病的临床疗效及不良反应。方法根据病情轻重、患者对维甲酸耐受情况,剂量个体化使用阿维A治疗中重度银屑病30例。结果30例病例均获得满意疗效,起效时间多数在于1周之内,4周内完全控制症状。仅1例因肝酶升高被终止治疗,均有不同程度的皮肤干燥、瘙痒、口干及唇炎等不良反应,经处理后能缓解。结论阿维A治疗银屑病疗效好,值得推广使用。     

Tildrakizumab: A Review in Moderate-to-Severe Plaque Psoriasis

American Journal of Clinical Dermatology - Tildrakizumab (tildrakizumab-asmn in the USA) [Ilumetri®; Ilumya™] is a humanized monoclonal antibody (mAb) that selectively targets the p19...     

Dermoscopy to Detect Signs of Subclinical Nail Involvement in Chronic Plaque Psoriasis: A Study of 68 Patients

Background:

Onychopathies constitute one of the major challenges faced by a dermatologist in terms of its early detection and diagnosis. Utility of dermoscope as a tool for detection is increasing by the day and its use in onychopathies needs to be explored.

Aims:

To study the dermoscopic features of nails in patients of chronic plaque psoriasis.

Materials and Methods:

In a cross-sectional study, a total of 68 patients with chronic plaque psoriasis were recruited. Dermoscopy of nail plate was conducted and were compared with equal number of age and sex matched healthy volunteers.

Results:

Forty-six patients showed dermoscopic findings. Twenty-two patients did not show any dermoscopic findings. Coarse pits (18/46, P < 0.0001), onycholysis (10/46, P < 0.001), oil drop sign (2/46, P = 0.12) and splinter hemorrhages (5/46, P = 0.05) were seen. In addition certain findings of interest were stout, globose, dilated, pink- to red-colored nail bed vessels arranged longitudinally at the onychodermal band surrounded by a prominent halo (9/46, P = 0.01). In contrast, splinter hemorrhages appeared as streaks and were purple in color.

Conclusion:

In a psoriasis patient, dermoscope can be a useful tool to detect early nail involvement in psoriasis and aid in differentiating it from other disorders of nails.     

[Translated article] Moderate to Severe Psoriasis in Pediatric and Young Patients: The BIOBADADERM Registry Experience

Childhood-onset psoriasis generally follows an indolent course but patients with moderate or severe disease may require systemic treatment. The aim of this study was to determine the relative proportion of children and young people aged up to 21 years with moderate to severe psoriasis in the BIOBADADERM registry and to analyze the characteristics of these patients, treatments used, and adverse events. Of the 3946 patients in the registry, 24 were aged 21 years or younger. The mean age of this group when they started treatment upon registration on Biobadaderm was 16.1 years and the mean Psoriasis Area and Severity Index was 9.4. In 67% the first treatment recorded was with a conventional systemic drug. Treatment was discontinued in 14 patients (58%) due to adverse events or a loss or lack of effectiveness. In conclusion, the BIOBADADERM registry shows that young people account for a small proportion of psoriasis patients receiving systemic treatment, and they are more likely to be treated using conventional systemic drugs.     

Safety and Efficacy of Subcutaneously Administered Efalizumab in Adults with Moderate-to-Severe Hand and Foot Psoriasis

Introduction: Hand and foot psoriasis may be more disabling than psoriasis at other body locations because of its interference with daily functional activities. Most treatment options have limited efficacy, short duration of response, toxicity, intolerability, or inconvenience. Objective: To investigate whether efalizumab (Raptiva®) is efficacious and safe for the treatment of patients with hand and foot psoriasis. Method: Adult patients with moderate-to-severe hand and/or foot psoriasis received a conditioning dose of efalizumab 0.7 mg/kg at week 0 with subsequent doses of efalizumab 1 mg/kg given weekly for 11 additional weeks (total of 12 doses). Patients were followed until week 24 (12 weeks after the last treatment) to monitor safety and efficacy. Static Physician’s Global Assessment (PGA) scores were used to measure efficacy. The primary efficacy endpoint was the number of patients achieving a 50% reduction in the global evaluation by static PGA from baseline at week 12. Results: Ten patients enrolled, six of whom completed the study. Of these six patients, four patients showed overall improvement at 12 weeks, including two patients that achieved 50% improvement overall. At 12 weeks, the hands of two patients and the feet of two patients showed at least 50% improvement from baseline. Efalizumab was well tolerated and there were no serious adverse events. Conclusion: Continuous treatment with efalizumab for 12 weeks was safe and efficacious in this open-label study of patients with hand and foot psoriasis.     

白芍总苷联合阿维A治疗中、重度银屑病32例临床观察

目的观察白芍总苷联合阿维A治疗中、重度银屑病的临床疗效和安全性。方法 62例中、重度银屑病患者随机分为2组,治疗组32例,予口服白芍总苷600mg3次/d,阿维A0.5mg/(kg.d)治疗,对照组30例仅予口服阿维A0.5mg/(kg.d)治疗,疗程8周。以银屑病皮损面积和严重程度(PASI)评分评价疗效并记录不良反应。结果治疗8周后,治疗组PASI评分(4.36±3.12)低于对照组(6.38±2.81),差异有统计学意义(P<0.05);治疗组有效率(90.62%)高于对照组(76.67%)。差异有统计学意义(P<0.05)。两组未见明显不良反应。结论白芍总苷联合阿维A治疗中、重度银屑病的患者疗效好,安全性高。     

Efficacy and Safety of the Betamethasone Valerate 0.1% Plaster in Mild-to-Moderate Chronic Plaque Psoriasis

Background: Corticosteroids are a versatile option for the treatment of mild-to-moderate psoriasis due to their availability in a wide range of potencies and formulations. Occlusion of the corticosteroid is a widely accepted procedure to enhance the penetration of the medication, thereby improving its effectiveness. Betamethasone valerate (BMV) is a moderately potent corticosteroid that is available as a cream, ointment, and lotion. A ready-to-use occlusive dressing, which provides a continuous sustained release of BMV, has been developed for the treatment of psoriasis. Objective: To evaluate the efficacy and safety of a new BMV 0.1% plaster compared with a BMV 0.1% cream in patients with mild-to-moderate chronic plaque psoriasis. Methods: This was a prospective, randomized, assessor-blind, parallel-group, active-controlled, multicenter, phase III study. Eligible outpatients (aged ≥18 years) with a diagnosis of stable, chronic plaque psoriasis vulgaris with two to four plaques on extensor surfaces of limbs were randomized to receive BMV 0.1% plaster or BMV 0.1% cream for 3–5 weeks; patients with resolution of target plaques then entered a 3-month, treatment-free, follow-up period. The number of patients showing clearing of plaques (remission) at 3 weeks (primary endpoint) and at 5 weeks was independently evaluated from digitized images of target plaques by two blinded assessors, and also assessed by the investigator and patient. Additional endpoints were (i) change from baseline in target plaque size and in Psoriasis Global Assessment (PGA) score, as evaluated by the blinded assessors, investigator, and patient; (ii) change from baseline in symptom (itching, soreness) severity; (iii) treatment satisfaction and ease of use; (iv) clearing and relapse during the follow-up period; and (v) adverse events (AEs). Results: Patients (n = 231) were screened and randomized to treatment with BMV 0.1% plaster (n = 116) and BMV 0.1% cream (n = 115). Significantly more patients achieved clearing after 3 weeks’ treatment with BMV plaster than with BMV cream (Cochran-Mantel-Haenszel test, p < 0.001); this difference was maintained at 5 weeks. The total plaque area decreased to a larger extent for the BMV plaster group compared with the BMV cream group (analysis of covariance [ANCOVA] model, p = 0.017 at week 5). PGA scores were significantly lower after 3 and 5 weeks’ treatment with BMV plaster (ANCOVA model, all p ≤ 0.016 vs BMV cream). Both treatments reduced itching and soreness to a similar degree, and the incidences of relapse during the follow-up period were comparable between treatment groups. There were no significant differences in AEs between treatment groups. Conclusions: BMV 0.1% plaster is more efficacious than BMV 0.1% cream in the treatment of patients with mild-to-moderate chronic plaque psoriasis in a clinical setting resembling daily clinical practice. Clinical trial number: ISRCTN68864186     

甲氨蝶呤联合小剂量叶酸治疗中重度银屑病疗效观察

目的观察小剂量叶酸配合甲氨蝶呤(methotrexate,MTX)治疗中重度银屑病临床疗效及安全性。方法124例银屑病患者随机分为治疗组与对照组。治疗组62例每周口服MTX7.5～15mg,每日口服叶酸5mg,共8周。对照组62例采用维生素A、维生素E、氨肽素及抗组胺药常规治疗。结果治疗12周和24周后,治疗组与对照组治疗后显效率经卡方检验,P<0.05,差异有显著性。两组均无严重不良反应。结论MTX每周口服7.5～15mg,同时补充小剂量叶酸治疗中重度银屑病有效。     

Economic Factors as Major Determinants of Ustekinumab Drug Survival of Patients with Chronic Plaque Psoriasis in Korea

BackgroundDrug survival, defined as the time until discontinuation, is a parameter reflecting real-world therapeutic effectiveness. Few studies have examined the influence of economic factors on the drug survival of biologic agents for psoriasis, particularly in Asian countries.ObjectiveTo determine the drug survival for ustekinumab in real-life settings and investigate the factors affecting drug survival for psoriasis patients in Korea.MethodsWe evaluated 98 psoriasis patients who were treated with ustekinumab at a single center. We analyzed the efficacy and drug survival of ustekinumab. Cox proportional hazard analysis and competing risk regression analysis were performed to reveal the factors affecting the drug survival of ustekinumab.ResultsThe overall mean drug survival was 1,596 days (95% confidence interval [CI], 904~2,288). Among the 39 cessations of ustekinumab treatment, 9 (23.1%) patients discontinued treatment after experiencing satisfactory results. Multivariate Cox proportional hazard analysis revealed that paying on patients'' own expense was the major predictor for the discontinuation of ustekinumab (hazard ratio [HR], 9.696; 95% CI, 4.088~22.998). Competing risk regression analysis modeling of discontinuation because of factors other than satisfaction of an event also revealed that ustekinumab treatment at the patient''s expense (HR, 4.138; 95% CI, 1.684~10.168) was a predictor of discontinuation rather than satisfaction.ConclusionThe results of our study revealed that the cost of biologics treatment affects the drug survival of ustekinumab and suggested that economic factors affect the drug survival of ustekinumab treatment in Korea.