Safety and efficacy of nivolumab in Japanese patients with malignant melanoma: An interim analysis of a postmarketing surveillance

A postmarketing surveillance study is ongoing to evaluate nivolumab treatment for Japanese patients with malignant melanoma and accumulate data on all adverse events (AE) and efficacy. In this interim analysis, we evaluated data from approximately 100 Japanese medical institutions obtained from the nivolumab approval date in Japan (4 July 2014) through 3 July 2016. Patients were monitored during the first 12 months of treatment. Nivolumab was administrated by i.v. infusion (2 mg/kg every 3 weeks). A total of 680 and 610 patients were evaluated for safety and efficacy, respectively. The incidences of adverse drug reactions (ADR) and grade 3 or higher ADR were 53.53% and 12.35%, respectively. Predominant ADR included hypothyroidism (11.32%) and abnormal enzyme activity, such as increase of aspartate aminotransferase (7.79%), alanine aminotransferase (6.76%), alkaline phosphatase (6.18%) and γ‐glutamyltransferase (5.44%). Grade 3 or higher ADR of special interest with an incidence of 1% or higher were hepatic function disorder (2.50%), colitis/diarrhea (2.06%) and infusion reaction (1.32%). No cases of encephalitis or venous thromboembolism, other AE of special interest, were observed. The estimated median overall survival was 379 days (95% confidence interval [CI], 290–not reached [NR]) in the overall population, NR (95% CI, 305–NR) for cutaneous melanoma and 340 days (95% CI, 275–NR) for mucosal melanoma. The improvement rate based on the antitumor response at the last evaluation was 22.2% (131/590 patients). No new safety concerns were raised, and serious ADR of special interest were infrequent. Nivolumab showed equivalent efficacy in patients with mucosal melanoma and those with cutaneous melanoma.     

Safety profiles and efficacy of infliximab therapy in Japanese patients with plaque psoriasis with or without psoriatic arthritis,pustular psoriasis or psoriatic erythroderma: Results from the prospective post‐marketing surveillance

A large‐scale prospective post‐marketing surveillance was conducted to evaluate the safety and efficacy of infliximab in Japanese patients with plaque psoriasis, psoriatic arthritis, pustular psoriasis and psoriatic erythroderma. This study was conducted in all psoriasis patients treated with infliximab after its Japanese regulatory approval. Infliximab was administrated at 5 mg/kg at weeks 0, 2 and 6, and every 8 weeks thereafter. Patients were serially enrolled and observed for 6 months to evaluate the safety and efficacy. The safety and efficacy were evaluated in 764 and 746 patients, respectively. Incidences of any and serious adverse drug reactions were 22.51% and 6.94%, respectively, and those of any and serious infusion reactions were 6.15% and 1.31%, respectively, which were comparable with the results in the post‐marketing surveillance with 5000 rheumatoid arthritis patients in Japan. Major adverse drug reactions during the follow‐up period were infections (5.10%) including pneumonia, cellulitis and herpes zoster, however, no tuberculosis was observed. The safety profiles were equivalent, regardless of the psoriasis types. No new safety problems were identified. The response rates on global improvement and median improvement rate of Psoriasis Area and Severity Index in all patients were 88.0% and 85.0%, respectively. Of note, the efficacy was equivalent for each psoriasis type as well as for each body region. Infliximab was also effective in pustular psoriasis symptoms, joint symptoms and nail psoriasis, as well as improvement of quality of life. Infliximab was confirmed to be highly effective and well tolerated in treating refractory psoriasis, including pustular psoriasis and psoriatic erythroderma.     

A phase IIIb,multicentre, randomized,double‐blind,vehicle‐controlled study of the efficacy and safety of adalimumab with and without calcipotriol/betamethasone topical treatment in patients with moderate to severe psoriasis: the BELIEVE study

Background Data are lacking on the use of topical therapies in combination with tumour necrosis factor blockers for the treatment of psoriasis. Objectives To assess the efficacy and safety of adalimumab (ADA) with topical calcipotriol/betamethasone (C/B) in patients with psoriasis resembling those treated in routine clinical practice. Methods A 16‐week, randomized, vehicle‐controlled trial was conducted in patients with moderate to severe psoriasis and previous failure, intolerance or contraindications to two or more systemic treatments. All patients received ADA (80 mg, week 0; 40 mg every other week, weeks 1–15) in addition to either topical C/B or drug‐free vehicle applied once daily for 4 weeks, and as needed thereafter. The primary endpoint was 75% improvement from baseline in Psoriasis Area and Severity Index (PASI 75) at week 16. Results A total of 730 patients received either ADA + C/B (n = 366) or ADA + vehicle (n = 364). PASI 75 response was initially higher with the combination therapy [14·8% for ADA + C/B vs. 5·8% for ADA + vehicle at week 2 (P < 0·001); and 40·7% vs. 32·4%, respectively, at week 4 (P = 0·021)]. After week 4, the trend was towards a higher response with ADA monotherapy, with no statistical difference in the PASI 75 response at week 16 (64·8% for ADA + C/B vs. 70·9% for ADA monotherapy, P = 0·086). Safety findings were consistent with previous ADA trials. Conclusions ADA + C/B resulted in more rapid and higher efficacy within the first 4 weeks; thereafter, the trend was towards a higher response with ADA monotherapy. There was no statistical difference in the PASI 75 response at week 16. Both treatment regimens were well tolerated.     

Fluctuations in serum levels of adalimumab and infliximab in patients on stable treatment for psoriasis

Many patients with psoriasis fail to respond to biologic drugs either initially or lose response over time, the latter having predominantly been linked to low circulating drug levels. We examined how serum drug levels varied over three treatment cycles of stable maintenance therapy with either adalimumab or infliximab among a total of 28 patients with psoriasis (22 men, mean age 48.6 years, mean treatment time 6.2 years) and whether there was an association with various patient‐specific factors. The range for all concentrations was 1.1 to 24.3 μg/mL for adalimumab and 0.0 to 180.6 μg/mL for infliximab. There was a consistent inverse association between body mass index (BMI) and trough and maximum serum concentrations of adalimumab (P < .05 for all comparisons) and a positive, less consistent, association between age and maximum serum concentration of infliximab (P < .05 for both comparisons). Patient‐specific factors, such as BMI and age, can help predict fluctuations in serum concentrations of biologics used for psoriasis.     

Impact of adalimumab treatment on cardiovascular risk biomarkers in psoriasis: Results of a pilot study

Psoriasis is a chronic systemic immune‐mediated inflammatory dermatosis associated with several comorbidities. Psoriasis patients are at increased risk of developing cardiovascular diseases (CVD), namely, coronary heart disease, stroke or peripheral vascular disease, and psoriasis seems to be an independent cardiovascular risk factor. Antipsoriatic systemic therapy, especially anti‐tumor necrosis factor (TNF)‐α, seems to exert a beneficial effect on these comorbidities. The purpose of this study was: (i) to measure the level of cardiovascular serum markers in psoriasis patients in comparison with healthy volunteers; and (ii) to compare the serum level of the same markers in patients before and 3 months after adalimumab therapy. We investigated six biomarkers connected to CVD: C‐reactive protein (measured high sensitively, hsCRP), oxidized low‐density lipoproteins (oxLDL), oxLDL/β‐glycoprotein I complex (oxLDL/β2GPI), vascular endothelial adhesion molecule 1 (VCAM‐1), E‐selectin and interleukin (IL)‐22. These biomarkers were measured in 21 patients with moderate/severe psoriasis before and after treatment with adalimumab and in healthy volunteers. hsCRP (P < 0.05), oxLDL‐β2GPI complex (P < 0.05), E‐selectin (P < 0.001) and IL‐22 (P < 0.001) were significantly increased in comparison with healthy controls, whereas oxLDL and VCAM‐1 were also higher in psoriasis patients but the difference did not reach statistical significance. A decrease of E‐selectin (P < 0.001) and IL‐22 (P < 0.001) was observed after 3 months of adalimumab therapy. Inhibition of TNF‐α seems to not only improve psoriasis but also decreases serum cardiovascular biomarkers. E‐selectin and IL‐22 could serve for monitoring of the efficacy of antipsoriatic systemic therapy on cardiovascular risk.     

Efficacy and safety of adalimumab in patients with psoriasis previously treated with anti‐tumour necrosis factor agents: subanalysis of BELIEVE

Background Few large clinical studies have evaluated whether switching tumour necrosis factor antagonists (anti‐TNFs) is likely to improve psoriasis in patients with prior anti‐TNF treatment. Objective The aim of this subanalysis of the BELIEVE study was to assess the efficacy and safety of adalimumab for psoriasis in patients with and without previous anti‐TNF treatment. Methods The BELIEVE study enrolled patients with moderate to severe psoriasis and prior failure, intolerance or contraindication to ≥2 systemic therapies. In this 16‐week, double‐blind, randomized, controlled trial, patients received adalimumab (80 mg, week 0; 40 mg every other week, weeks 1–15) with either topical vehicle or topical calcipotriol/betamethasone dipropionate (C/B) applied once daily for 4 weeks, then as needed. The primary endpoint was ≥75% improvement from baseline in Psoriasis Area and Severity Index score (PASI 75) at week 16. This post hoc subanalysis evaluated the safety and efficacy of adalimumab, with and without topical therapy, in BELIEVE patients who had prior exposure to anti‐TNFs. Results Of 730 patients enrolled, 282 (38.6%) had prior anti‐TNFs and 448 (61.4%) were anti‐TNF‐naïve. Combining topical vehicle and topical C/B study populations, 61.7% of patients with prior anti‐TNFs achieved PASI 75 at week 16, compared with 71.7% of anti‐TNF‐naïve patients (P = 0.095). Adalimumab resulted in clinically meaningful improvement regardless of which prior anti‐TNF agent had been used, the number of prior anti‐TNFs tried, or reasons for discontinuation of prior anti‐TNF therapy. Adverse event incidences were similar between patients with and without prior anti‐TNF therapy. Conclusion Adalimumab was effective and well‐tolerated in patients with psoriasis previously treated with anti‐TNF therapy.     

Long-term safety of brodalumab in Japanese patients with plaque psoriasis: An open-label extension study

Brodalumab, an interleukin-17 receptor A inhibitor, demonstrated rapid and robust efficacy with a favorable safety profile in patients with moderate to severe plaque psoriasis. Here, we present data from a multicenter, open-label extension study in patients with plaque psoriasis with/without psoriatic arthritis who completed 64 weeks of treatment with brodalumab (140 or 210 mg, every 2 weeks [Q2W]). Patients were enrolled to evaluate the long-term safety and efficacy of a modified dose of brodalumab. Eligible patients were switched to a reduced dose of brodalumab (140 mg every 4 weeks on day 1) in the extension study; the dose and dosing interval were modified sequentially at the physician’s discretion (minimum 140 mg every 8 weeks and maximum 210 mg Q2W) until drug approval, after which all patients were switched to 210 mg Q2W for postmarketing surveillance. Of the 129 patients enrolled, 107 (82.9%) completed the 108-week or more extension study. All patients had psoriasis that was well controlled with brodalumab treatment on day 1. Improvement in psoriasis-related symptoms, evaluated with the Psoriasis Area and Severity Index, Psoriasis Scalp Severity Index, Dermatology Life Quality Index, Nail Psoriasis Severity Index, and American College of Rheumatology 20, 50 and 70, was maintained during the 108-week extension study. Brodalumab treatment was well tolerated throughout, and no new safety signals were identified. The most commonly reported treatment-related adverse event was nasopharyngitis, followed by influenza and oral candidiasis. No cases of serious candida infection or Crohn’s disease were observed in this study. Serious treatment-related adverse events, such as appendicitis, brain abscess, bacterial meningitis, colon cancer, immunoglobulin A nephropathy and tubulointerstitial nephritis, were reported in one patient each. No anti-brodalumab-binding antibodies or brodalumab-neutralizing antibodies were detected in any patient throughout the extension study. Overall, the long-term efficacy and safety of brodalumab were demonstrated over 108 weeks.     

阿达木单抗治疗重度银屑病的疗效观察

目的观察阿达木单抗治疗重度银屑病的效果。方法在我院皮肤科2016年9月~2018年10月收治的重度银屑病患者中选出135例为对象,随机将患者分为对照组和观察组,对照组患者给予常规西医治疗(阿维A、雷公藤多苷片和卡西醇软膏),观察组患者在对照组基础上应用阿达木单抗治疗,对比两组的治疗总有效率等。结果观察组治疗总有效率为95.52%,高于对照组治疗总有效率(82.35%),P<0.05;不良反应发生率对比,观察组13.43%,与对照组17.65%差异不明显,P>0.05。结论阿达木单抗在重度银屑病患者治疗中的应用效果确切,且用药安全性高。     

Results of a retrospective study on the efficacy and safety of adalimumab 80 mg administrated every other week in patients with psoriasis at a single Japanese institution

Adalimumab (ADA) is one of the tumor necrosis factor (TNF)‐α monoclonal antibodies used for the treatment of psoriasis. In Japan, standard dosing of ADA for adults is an initial s.c. injection of 80 mg, followed by 40 mg every other week. Some patients who initially do not respond to treatment are allowed an increased dose of 80 mg every other week. However, studies on the efficacy and safety of ADA dose escalation to 80 mg every other week are few. In this study, we retrospectively studied 92 patients with psoriasis who received ADA therapy in our hospital. In 45 out of 92 patients, the dose of ADA 80 mg was administrated every other week, and the efficacy was observed within 12 weeks. The most common adverse drug reaction was upper respiratory infection, followed by diarrhea. In three patients, malignancies occurred during the observation period. No deaths or other severe complications were observed. In conclusion, this study showed the efficacy and safety of ADA dose escalation to 80 mg every other week in patients with psoriasis.     

Switching from etanercept to adalimumab is effective and safe: results in 30 patients with psoriasis with primary failure,secondary failure or intolerance to etanercept

Background Knowledge on the sequential treatment of psoriasis with biologics with regard to efficacy and safety is sparse. This also applies to the efficacy and safety of adalimumab in patients previously treated with etanercept. The relationship between the reasons for discontinuation of etanercept and the response to adalimumab is not clear in psoriasis. Objectives To evaluate the efficacy and safety of adalimumab in patients with psoriasis with primary failure, secondary failure or intolerance to etanercept in daily practice. Methods Data were extracted from two prospective registries from all patients with psoriasis with failure on etanercept treatment, who switched to adalimumab therapy. Thirty patients fulfilled these criteria. All patients were naive to biologics when etanercept was initiated. Primary endpoints were the percentage of patients achieving a 50% or 75% improvement of the baseline Psoriasis Area and Severity Index (PASI) score (PASI 50 and PASI 75, respectively) at weeks 12, 24 and 48. Secondary endpoints were the percentage of patients achieving PASI 90, the mean percentage improvement in the PASI score from baseline and the adverse event rate. Results Compared with the baseline PASI score before the start of etanercept, the mean percentage improvement in PASI and the PASI 50/75/90 response rates to adalimumab until week 48 were comparable to those achieved with etanercept. In the patients failing on etanercept, PASI 75 was achieved by 27%, 36% and 54% at weeks 12, 24 and 48 of adalimumab treatment, respectively. The majority of patients showed a beneficial response to adalimumab, irrespective of the reason for discontinuation of etanercept. Previous treatment with etanercept did not increase the adverse event rate nor change the nature of the side‐effects. Conclusions Adalimumab seems to be an effective and safe treatment option for patients with psoriasis who failed on etanercept treatment irrespective of the reason for discontinuation.     

Treatment of nail psoriasis with adalimumab: an open label unblinded study

Background Despite numerous advances in the therapeutic management of cutaneous psoriasis, there is a lack of standardized therapeutic regimens for psoriatic nail disease. Objective An open, non‐randomized, unblinded study was designed to evaluate the efficacy and safety of adalimumab in the treatment of nail psoriasis. Patients/methods Seven patients suffering from severe plaque‐type psoriasis and 14 with psoriatic arthritis and cutaneous psoriasis with concomitant nail involvement were enrolled into the study. The applied dose regimen of adalimumab was the same as the one recommended for cutaneous psoriasis. Outcome measures were assessed at baseline and at weeks 12 and 24 using the Nail Psoriasis Severity Index (NAPSI). Patients also filled in a Greek translation of the international onychomycosis‐specific questionnaire to assess the impact of the nail improvement on their quality of life. Results All 21 patients completed the study and were eligible for statistical analysis. Significant improvement was recorded after the eighth injection. Mean NAPSI (NAPSIm) at baseline was 10.57 ± 1.21 for the fingernails and 14.57 ± 2.50 for the toenails in patients with just cutaneous psoriasis and 23.86 ± 2.00 for the fingernails and 29.29 ± 2.87 for the toenails in patients with psoriatic arthritis. NAPSIm at week 12 was 5.57 ± 0.78 for the fingernails and 9.57 ± 2.17 for the toenails in patients with just cutaneous psoriasis and 12.86 ± 1.05 for the fingernails and 19.21 ± 2.07 for the toenails in patients with psoriatic arthritis. NAPSIm after 24 weeks of treatment was 1.57 ± 0.20 for the fingernails and 4.14 ± 1.58 for the toenails in patients with cutaneous psoriasis and 3.23 ± 0.32 for the figernails and 10.00 ± 1.40 for the toenails in patients with psoriatic arthritis. Treatment was well tolerated with minimal and temporary side‐effects limited to the site of injection. All patients were satisfied, while marked improvement in their quality of life was recorded based on the reduction of the scores obtained from the international quality of life questionnaire. Conclusions Despite the lack of a control group, our results demonstrate a beneficial effect of adalimumab on psoriatic nail disease.     

Relationship between the efficacy of biologics and clinical plaque psoriasis subtypes in Japanese patients: A single‐center pilot study

Although biologics for plaque psoriasis brought epoch‐making efficacy, not all patients achieve treatment success with all reagents. The aim of this study was to clarify the correlation between clinical plaque psoriasis subtypes, age at onset, and the efficacy of biologics. Clinical records for patients with plaque psoriasis at Fukuoka University Hospital were reviewed retrospectively. The efficacy of biologics was compared using the survival of the first biologics administered in treatment‐naïve patients. The survival of infliximab, adalimumab, and ustekinumab were followed until December 2016. The patients were clinically classified into three subtypes: small, large, or gigantic plaques using the size of the plaques on the back; early onset psoriasis (EOP, onset <40 years); or late‐onset psoriasis (LOP, ≥40 years). Eighty‐seven patients were enrolled. The survival of biologics was significantly better in large plaques compared with small or gigantic plaques (P = 0.0007). In patients treated with tumor necrosis factor (TNF) inhibitors, large plaques had significantly better survival than did the other types (P = 0.0122), while ustekinumab showed good survival in all three subtypes. The survival of biologics was numerically better in EOP than in LOP, but this was not significant. The efficacy of TNF inhibitors was different among clinical subtypes. Psoriatic patients with small plaques may be less responsive to TNF inhibitors. Further studies are needed.     

Digoxin use and following risk of psoriasis: A population-based cohort study in Taiwan

This study examined the association between digoxin use and subsequent psoriasis risk using a population-based database in Taiwan. This cohort study enrolled 15 545 digoxin users and 15 545 propensity score-matched non-users from the Taiwan National Health Insurance Research Database. Each patient was independently followed up for 5 years to confirm whether they had been diagnosed with psoriasis. Cox proportional hazard regression was used to estimate psoriasis risk among digoxin users. Subgroup and sensitivity analyses were also performed. The psoriasis incidence rates were 3.02 and 2.27 per 1000 person-years among digoxin users and non-users, respectively. After adjustment for confounders, psoriasis risk was significantly higher among digoxin users than among non-users. Notably, in most subgroup analyses, digoxin use tended to increase psoriasis risk, particularly among patients with heart failure, diabetes, hypertension and hyperlipidaemia. Moreover, significantly increased psoriasis risk was noted over 2, 3, 4 and 5 years of digoxin use. In conclusion, our findings confirm that digoxin use increases subsequent psoriasis risk. Thus, physicians should be aware of this association and accordingly estimate the risks and benefits of digoxin use. Nevertheless, some patient variables, such as body mass index and obesity, were unavailable in this study. The findings in this study should be elucidated carefully because the potential effects of these factors could not be considered.     

Infliximab efficacy in nail psoriasis. A retrospective study in 48 patients

Background Nail psoriasis occurs in up to half of psoriatic patients and can lead to significant physical impairment and pain. To date, patients and clinicians are actually dissatisfied by current therapeutic approaches. Objective Our main aim is to evaluate Infliximab efficacy in nail psoriasis. Methods We performed an open‐label and uncontrolled retrospective study considering all psoriatic patients presenting recalcitrant nail involvement and receiving Infliximab in our Department during the period between January 2008 and March 2009. We calculated nail psoriasis severity index (NAPSI) score at 0, 14, 22 and 38 weeks and percentage of patients achieving NAPSI‐50,‐75,‐90 at 14, 22 and 38 weeks. Results We observed a rapid nail improvement in most cases after 22 weeks of Infliximab therapy, but a complete nail clearing was reached in only five (10.4%) patients. We don’t have a follow‐up longer than 38 weeks to assess long‐term efficacy of this treatment in nail psoriasis. Conclusions Infliximab, in our experience, has proved to be effective in reducing nail lesions and, in some cases, even clearing them. Our data demonstrate long‐term efficacy of this biological agent in nail psoriasis.     

Effects of maxacalcitol ointment on skin lesions in patients with psoriasis receiving treatment with adalimumab

Adalimumab is a biologic that is very effective for treatment of psoriasis. However, recalcitrant or recurrent lesions sometimes occur during treatment. Maxacalcitol is an active vitamin D3 ointment that is effective in treatment of psoriasis. Topical therapy may be beneficial in treatment of recalcitrant or recurrent lesions during treatment with systemic therapy, but there is little evidence on this topic. We investigated the effect of maxacalcitol on skin lesions during treatment with adalimumab in patients with psoriasis. Twelve patients with psoriasis were randomly assigned to two groups after informed consent – treatment with adalimumab only (n = 6), and treatment with adalimumab and maxacalcitol (n = 6) – and they were evaluated every 4 weeks for 44 weeks. Exacerbation was defined as an increase of the Psoriasis Area and Severity Index (PASI) score. The interval between adalimumab treatments was elongated to 3–4 weeks from 2 weeks according to the individual patient's condition. The PASI score was evaluated every 4 weeks, and the frequency of exacerbations was counted. The overall improvement in PASI score was not statistically different between the two groups, but the frequency of exacerbations was significantly less in the maxacalcitol combination group compared with the adalimumab monotherapy group (Mann–Whitney U‐test, P < 0.05). The better control of skin lesions in patients who elongated the interval of adalimumab administration was achieved in the maxacalcitol combination group compared with the adalimumab monotherapy group. Topical maxacalcitol treatment is effective and useful in controlling skin lesions in patients with psoriasis when used in combination with adalimumab.     

Utility of the Dermatology Life Quality Index at initiation or switching of biologics in real-life Japanese patients with plaque psoriasis: Results from the ProLOGUE study

BackgroundPlaque psoriasis significantly affects patients’ health-related quality of life. To aid treatment decisions, not only objective assessment by physicians but also subjective assessment by patients is important.ObjectiveTo assess the significance of Dermatology Life Quality Index (DLQI) evaluation at the time of biologics introduction in clinical practice in Japanese patients with plaque psoriasis.MethodsThis was a single-arm, open-label, multicenter study. At baseline, Psoriasis Area and Severity Index (PASI) and DLQI scores were measured and stratified based on DLQI scores ≥6/≤5 and PASI scores ≤10/>10. Other patient-reported outcomes assessed included EQ-5D-5L, itch numerical rating scale (NRS), skin pain NRS, Generalized Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-8 (PHQ-8), Sleep Problem Index-II (SPI-II), and Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9).ResultsOf the 73 enrolled patients, 23 had PASI scores ≤10. Those with PASI/DLQI scores >10/≥6 had a significantly higher median PASI score than those with PASI/DLQI scores >10/≤5 (p = 0.0125). Regardless of PASI scores (>10/≤10), median itch NRS and GAD-7 scores were significantly higher in patients with DLQI scores ≥6 than in those with DLQI scores ≤5 (itch NRS, p = 0.0361 and p = 0.0086, respectively; GAD-7, p = 0.0167 and p = 0.0273, respectively). Patients with PASI/DLQI scores ≤10/≥6 had significantly higher skin pain NRS (p = 0.0292) and PHQ-8 (p = 0.0255) scores and significantly lower median SPI-II scores (p = 0.0137) and TSQM-9 Effectiveness domain scores (p = 0.0178) than those with PASI/DLQI scores ≤10/≤5.ConclusionDLQI may be useful for assessing patients’ concerns that cannot be identified by PASI alone while initiating biologics or switching from other biologics in clinical practice.     

Adalimumab treatment optimization for psoriasis: Results of a long‐term phase 2/3 Japanese study

The tumor necrosis factor‐α inhibitor, adalimumab, is approved to treat moderate‐to‐severe plaque psoriasis (40 mg every‐other‐week or 80 mg every‐other‐week following inadequate response at 40 mg in Japan). This open‐label extension (OLE) trial evaluated the optimal adalimumab dose for long‐term efficacy and safety in Japanese patients with moderate‐to‐severe plaque psoriasis following a prior 24‐week, phase 2/3, randomized, double‐blind study. Of the 169 patients from the phase 2/3 trial, 147 entered the OLE on 40 mg (n = 89) or 80 mg (n = 58) adalimumab every‐other‐week. Patients on 40 mg with Psoriasis Area and Severity Index (PASI) of less than 50 could escalate to 80 mg. At week 52 (28 of OLE), patients entering the OLE on 80 mg were reduced to 40 mg, with the option to re‐escalate. For patients entering the OLE on 40 mg, final PASI 50/75/90 response rates were 85.1%/73.3%/60.4%, respectively, including effects of dose escalation. Among patients whose dose was escalated, final PASI 50/75/90 response rates were 70.0%/53.3%/36.7%, respectively. For patients entering the OLE on 80 mg, final PASI 50/75/90 response rates were 92.5%/84.9%/73.6%, respectively, including effects of dose re‐escalation. Overall incidence rates of adverse events (AE) and injection‐site reaction AE declined over time; rates for serious AE and infections were generally stable. Clinically meaningful efficacy of adalimumab was sustained to 4 years. Dose escalation to 80 mg every‐other‐week for patients with suboptimal response to 40 mg every‐other‐week, and dose reduction to 40 mg every‐other‐week for patients satisfactorily controlled on 80 mg every‐other‐week, are viable strategies for adalimumab optimization.     

Efficacy and safety of ustekinumab treatment in elderly patients with psoriasis

The ratio of the elderly among psoriasis patients has been increasing. However, satisfactory long‐term management of psoriasis for the elderly is challenging because of the more frequent presence of comorbidities, and the higher risk of adverse events from systemic therapeutic agents than younger patients. The use of ustekinumab (UST) appears to be an appropriate systemic treatment because it is considered less likely to cause adverse events than other systemic treatments, as well as necessitating fewer hospital visits. Our retrospective study aimed to evaluate the efficacy and safety profile of UST in elderly patients with psoriasis. The study included 24 patients aged over 65 years (range, 65–88 years; mean, 73.1 years) with moderate to severe plaque psoriasis with impaired quality of life. Efficacy and safety were assessed over a 1‐year period using the Psoriasis Area and Severity Index (PASI) and the Dermatology Live Quality Index (DLQI). The efficacy was evaluated by the proportion of subjects who achieved ≥75% reduction in PASI score (PASI 75). PASI 75 responses were 56.5% at week 16, 59.1% at week 28, and 60.0% at week 52. None of the patients developed any serious infection during the 1‐year treatment. The mean DLQI score at weeks 0, 16, 28, and 52 was 7.8 ± 6.0, 2.5 ± 3.4, 1.4 ± 1.7, and 1.2 ± 1.7, respectively. UST showed sufficient efficacy for elderly patients with psoriasis without any serious infection over the 1‐year treatment. Our results suggest that UST is the preferable agent for the treatment of elderly patients with psoriasis.