Treatment effect of adalimumab and infliximab in Japanese psoriasis patients: results in a single community-based hospital

Because adalimumab and infliximab were approved in Japan for psoriasis treatment only 1 year ago, therapeutic efficacy of these agents is not well studied in a Japanese psoriasis population. Moreover, the evaluation of scalp psoriasis treated with biologics has never been reported in these subjects. In this study, 21 patients with moderate to severe plaque psoriasis were assigned to receive adalimumab 40 mg every other week with an initial loading dose of 80 mg (n = 11), or infliximab 5 mg/kg at weeks 0, 2, 6, 14 and 22 (n = 10). The treatment efficacy was evaluated by the proportion of patients who achieved at least 75% improvement in Psoriasis Area and Severity Index (PASI 75) and Psoriasis Scalp Severity Index score (PSSI 75) from baseline at weeks 4, 8, 16 and 24. A patient selection bias existed between the two groups in body surface area and PASI (44.0 ± 24.7 vs 30.2 ± 13.5, P = 0.12 and 22.2 ± 9.3 vs 15.6 ± 7.75, P = 0.09, respectively). At week 16, 81.8% of adalimumab-treated patients and 60.0% of infliximab-treated patients achieved PASI 75 response, but no statistically significant difference was found between these response rates. There was a tendency toward a reduced PSSI 75 response rate in the adalimumab-treated group compared to the infliximab-treated group (54.5% vs 90% at week 16, P =0.15). In conclusion, both of the tumor necrosis factor-α inhibitors demonstrated good therapeutic response similar to that in the previously reported randomized controlled trials, without any severe adverse reactions. Treatment response in scalp lesions tended to be lower in adalimumab-treated patients, possibly because of delayed treatment onset of adalimumab.     

Adalimumab in Japanese patients with moderate to severe chronic plaque psoriasis: Efficacy and safety results from a Phase II/III randomized controlled study

Incidence of psoriasis vulgaris in Asians is estimated at 0.05–0.3%. Studies in North America and Europe demonstrated that adalimumab, a fully human, recombinant, immunoglobulin G₁ monoclonal antibody, was efficacious and well‐tolerated in patients with chronic plaque psoriasis. This 24‐week, placebo‐controlled study evaluated the efficacy and safety of three different dosing regimens of adalimumab in Japanese patients with moderate to severe chronic plaque psoriasis (n = 169). Patients were randomized to receive adalimumab 40 mg every other week (eow), adalimumab 80‐mg loading dose at week 0 followed by adalimumab 40 mg eow starting at week 2, adalimumab 80 mg eow, or placebo eow given as s.c. injections. The primary efficacy endpoint was the percentage of patients achieving a 75% or greater improvement in Psoriasis Area and Severity Index (PASI 75) score at week 16. At week 16, PASI 75 response rates were significantly greater for all three adalimumab groups (40 mg eow: 57.9%, P < 0.001; 40 mg eow plus loading dose: 62.8%, P < 0.001; 80 mg eow: 81.0%, P < 0.001) versus placebo (4.3%). As early as week 4, the 40‐mg eow plus loading dose and 80‐mg eow groups achieved significantly greater PASI 75 response rates compared with placebo. Injection‐site reactions and hepatic events occurred in greater percentages of adalimumab‐treated patients compared with placebo. Adalimumab therapy demonstrated efficacy and safety at all three dosage regimens. Rapid response rate in patients receiving 40 mg eow plus loading dose supports using an 80‐mg loading dose in the treatment of psoriasis.     

Relationship between methotrexate dosing and clinical response in patients with moderate to severe psoriasis: subanalysis of the CHAMPION study

Background CHAMPION was a phase III trial that compared adalimumab with methotrexate and placebo for chronic plaque psoriasis. Objectives To determine the relationship between methotrexate dosing and improvement in psoriasis for patients in CHAMPION. Methods Methotrexate‐treated patients in CHAMPION received step‐up dosing to 15 mg per week during the first 8 weeks. At week 8, PASI 50 responders (early responders, ER) were to continue with 15 mg weekly for the next 8 weeks; PASI 50 nonresponders were to receive 20 mg weekly for the next 4 weeks, followed by 20 mg weekly if they achieved ≥ PASI 50 at week 12 (late responders, LR), or 25 mg weekly if not (late nonresponders, LN). Outcomes were assessed post hoc for patients in these groups who completed CHAMPION. Results One hundred and three methotrexate‐treated patients were analysed: 40 ER, 22 LR and 41 LN. Week 16 mean percentage improvement from baseline in Psoriasis Area and Severity Index was greatest in the ER group, nearly as good in LR, and poor in LN; PASI 75/90/100 response rates were 70%/32%/18%, 41%/9%/5% and 5%/0%/0%, respectively. Among patients with a PASI 75 response at week 16, 72% were in the ER group (comprising 27% of patients overall) and 23% were in the LR group. Conclusions Nearly all week 16 PASI 75 responders in CHAMPION achieved a PASI 50 response at week 8 or 12, with maximum methotrexate dosages of 15 or 20 mg per week, respectively. Week 12 may be an appropriate time to discontinue methotrexate treatment in patients who are not achieving good responses.     

Long‐term outcomes of interruption and retreatment vs. continuous therapy with adalimumab for psoriasis: subanalysis of REVEAL and the open‐label extension study

Background REVEAL was a 52‐week study of adalimumab for moderate to severe psoriasis. At Week 33, adalimumab‐treated patients with sustained responses (PASI ≥75 at Weeks 16 and 33) were re‐randomized to receive adalimumab or placebo. Subsequently, they could receive adalimumab in an open‐label extension (OLE) study. Objective To compare long‐term efficacy and safety of adalimumab 40 mg every other week (eow), given as continuous treatment or with one period of interruption followed by retreatment. Methods Patients who were re‐randomized to adalimumab or placebo at REVEAL Week 33 and received ≥1 dose of OLE adalimumab were analysed as the continuous and retreatment groups, respectively, for >2 years of OLE treatment with adalimumab 40 mg eow. LOCF was used for missing efficacy data. Results At OLE Weeks 0, 12 and 24, PASI 75 response rates were 84%, 84%, 86% with continuous treatment (N = 233) vs. 45%, 71%, 79% with retreatment (N = 227). Thereafter, efficacies were slightly greater for continuous treatment but similar between groups, with PASI 75 response rates at OLE Week 108 of 75% vs. 73% respectively. Retreatment was most effective for patients with ≥PASI 50 responses when retreatment was initiated. Adverse event rates for retreatment were equal to or lower than those for continuous treatment. Conclusions In psoriasis patients with sustained PASI 75 responses to adalimumab, long‐term efficacy of retreatment after a ≤19‐week interruption was similar to efficacy achieved with >3 years continuous treatment. Adalimumab retreatment provided the best results when initiated before responses had declined below PASI 50.     

Adalimumab

▲ Adalimumab is a recombinant, human, IgG1 monoclonal antibody specific for tumor necrosis factor. ▲ The clinical efficacy and safety of adalimumab (40 mg administered subcutaneously every other week) in patients with moderate-to-severe chronic plaque psoriasis have been demonstrated in several randomized, double-blind clinical trials, including the pivotal trials REVEAL (n = 1212) and CHAMPION (n = 271). ▲ Based on these trials, adalimumab was significantly more effective than placebo and methotrexate at relieving the signs and symptoms of psoriasis after 16 weeks of treatment, as assessed by the percentage of patients achieving a 75% improvement from baseline in Psoriasis Area and Severity Index. Based on open-label extension studies of up to 2 years’ duration, the efficacy of adalimumab was sustained over the long term. ▲ Of patients who had responded to 33 weeks of treatment with adalimumab in REVEAL, patients randomized to remain on adalimumab for an additional 19 weeks of treatment were significantly less likely to experience loss of an adequate response than patients who were transferred to placebo. ▲ Compared with placebo or methotrexate, adalimumab was associated with significantly greater improvements in dermatology-specific and general measures of health-related quality of life in patients with plaque psoriasis. ▲ Adalimumab was generally well tolerated in trials in patients with plaque psoriasis, and the adverse-event profile was similar to that associated with its use in rheumatoid arthritis.     

Efficacy and safety of adalimumab when added to inadequate therapy for the treatment of psoriasis: results of PRIDE, an open-label, multicentre, phase IIIb study

Background Adalimumab is an effective treatment for chronic plaque psoriasis. Objective To evaluate the safety and efficacy of adalimumab for psoriasis patients who did not adequately respond to prior psoriasis therapy. Methods PRIDE (an Open‐Label Access PR ogram to Evaluate the Safety and Effectiveness of Adalimumab When Added to I naDE quate Therapy for the Treatment of Psoriasis) was a multicentre, Phase IIIb study in Canada. Patients with active moderate‐to‐severe plaque psoriasis who failed to respond to, or were intolerant of, prior therapies received adalimumab 80 mg at Week 0 followed by adalimumab 40 mg every other week Weeks 1 through 23. The primary efficacy measure was PASI (Psoriasis Area Severity Index) 75 response at Week 16. Secondary efficacy measures included PASI 90/100 and percentage change from baseline PASI score. Adverse events (AEs) and serious AEs were recorded. Results A total of 203 patients were enrolled at 26 sites. Baseline characteristics were: male, 61.1%; mean age, 45.5 years; mean PASI score, 20.0; previous exposure to biologics, 38.4%. At Week 16, PASI 75/90/100 responses were achieved by 70.9%/49.3%/24.1% of patients, respectively. Mean percentage PASI score decrease from baseline to Week 16 was 79.5%. Mean percentage PASI improvement and response rates were maintained through Week 24. Nasopharyngitis and upper respiratory tract infection were the only AEs to occur in ≥5% of patients. Nine patients experienced serious AEs; four were considered possibly or probably related to adalimumab. Conclusion Adalimumab was safe, well‐tolerated and effective for treatment of active plaque psoriasis in patients who had not adequately responded to prior therapy.     

阿达木单抗治疗重度斑块状银屑病的临床观察

【摘要】 目的 观察阿达木单抗治疗重度斑块状银屑病的疗效及安全性。方法 选取2018年6月至2019年4月就诊于河南省人民医院皮肤科的20例重度斑块状银屑病患者，首次治疗予皮下注射阿达木单抗80 mg，之后第1、3、5、7、9、11周注射40 mg，于第4、8、12周时观察并记录患者银屑病皮损面积和严重度指数（PASI），采用反射式共聚焦显微镜观察皮损的演变情况。治疗过程中监测不良反应。结果 4周时，12例PASI改善率达50%（PASI50）；8周时，14例达PASI75；12周时，20例达PASI 75，其中5例达PASI90，2例达PASI100。治疗前，RCM下皮损区域基底层黑素较皮损周围正常皮肤减少，治疗4周时较治疗前逐渐恢复；12周时基本恢复正常水平。20例患者均未发生感染、肿瘤等相关不良反应。结论 隔周皮下注射阿达木单抗治疗重度银屑病临床疗效显著，相关不良反应少。     

The efficacy of methotrexate plus pioglitazone vs. methotrexate alone in the management of patients with plaque‐type psoriasis: a single‐blinded randomized controlled trial

Recently, thiazolidinediones have shown to be efficacious with a favorable safety profile when used in the treatment of chronic plaque‐type psoriasis. The aim of this study was to evaluate and compare the efficacy and safety of a combination of methotrexate plus pioglitazone and methotrexate alone in plaque‐type psoriasis. A total of 44 adult patients with plaque‐type psoriasis were included in the study. Patients were randomized to treatment with methotrexate alone (group A) or methotrexate plus pioglitazone (group B) for 16 weeks. The primary efficacy outcome measure was psoriasis area and severity index (PASI) score change between the study groups at week 16 relative to baseline. The secondary efficacy outcome measure was dermatology life quality index (DLQI) score change between the two groups at week 16 relative to baseline. The PASI 75 score was also measured. After 16 weeks of therapy, the percentage of reduction in the mean PASI score was 70.3% in group B and 60.2% in group A. PASI 75 was achieved in 14 patients (63.6%) in group B compared with two patients (9.1%) in group A within 16 weeks, which was significant (P < 0.001). At 16 weeks from the baseline, a 63.6% decrease in the mean DLQI score of group B was seen, while the decrease for group A was 56.9%. Pioglitazone enhances the therapeutic effect of methotrexate in plaque‐type psoriasis, as demonstrated by a reduction in the mean PASI scores. In terms of DLQI, there was no extra benefit by the addition of pioglitazone to methotrexate therapy.     

Adalimumab treatment for severe recalcitrant chronic plaque psoriasis

Aim.  To assess the efficacy and safety profile of adalimumab in patients with severe, recalcitrant chronic plaque psoriasis, and to assess short-term overlapping of other systemic treatment with adalimumab to prevent flaring of disease.
Methods.  This was a retrospective study comprising 39 patients with chronic plaque psoriasis treated with adalimumab between October 2005 and January 2008. All had failed treatment with other systemic agents, including biological therapies in 59% of patients. Patients were started on adalimumab 40 mg weekly or fortnightly, as clinically indicated. Severity of psoriasis was assessed by the Psoriasis Area and Severity Index (PASI). Therapeutic response was assessed by 75% improvement on PASI (PASI 75). All adverse events were recorded.
Results.  Results were analysed separately for those treated with adalimumab only and those on combination treatment. PASI 75 was achieved in 38% (8 of 21 patients at week 16), 62% (13 of 21 patients) at week 24, 69% (9 of 13 patients) at week 48% and 71% (5 of 7 patients) at week 72 in the adalimumab-only group, compared with 56% (5 of 9 patients) at week 16, 50% (4 of 8 patients) at week 24, 80% (4 of 5 patients) at week 48% and 67% (2 of 3 patients) at week 72 in the combined group. Of the 39 patients, 15 (38%) achieved a PASI of 0 at some point in their treatment. Adalimumab was well tolerated; 38% of patients experienced side-effects, which were generally mild.
Conclusion.  Adalimumab was effective in a group of patients with psoriasis refractory to other systemic therapies, including biological treatments, and was well tolerated.     

Efficacy and safety of infliximab vs. methotrexate in patients with moderate-to-severe plaque psoriasis: results of an open-label, active-controlled, randomized trial (RESTORE1)

Background Infliximab is indicated for treatment of moderate‐to‐severe plaque psoriasis in adults whose disease cannot be controlled with other systemic therapies, including methotrexate (MTX). To date, no studies have directly compared the efficacy and safety of infliximab and MTX. Objectives To compare the efficacy and safety of infliximab vs. MTX in adults with moderate‐to‐severe plaque psoriasis. Methods MTX‐naïve patients (n = 868) were randomized 3 : 1 to receive infliximab 5 mg kg^?1 at weeks 0, 2, 6, 14 and 22 or MTX 15 mg weekly with a dose increase to 20 mg weekly at week 6 if the Psoriasis Area and Severity Index (PASI) response was < 25%. At week 16, patients with < PASI 50 response could switch treatment groups. The primary efficacy endpoint was PASI 75 response at week 16. Major secondary efficacy endpoints were PASI 75 response at week 26, and the proportion of patients achieving a Physician’s Global Assessment (PGA) score of cleared (0) or minimal (1) at weeks 16 and 26. Others included Dermatology Life Quality Index, 36‐Item Short Form Health Survey, and PGA, PASI 50, PASI 75 and PASI 90 responses over time. Results The primary endpoint was achieved by a significantly greater proportion of infliximab‐treated patients (508/653, 78%) than MTX‐treated patients (90/215, 42%; P < 0·001). Key secondary endpoints also were achieved by a greater proportion of infliximab‐treated patients. Similar responses were observed at week 26 in patients who switched from MTX to infliximab at week 16. Overall adverse event (AE) incidence was comparable between groups, but incidence of serious and severe AEs was slightly higher in the infliximab group. Conclusions Infliximab was well tolerated and more efficacious than MTX in patients with moderate‐to‐severe plaque psoriasis. Infliximab also was efficacious in patients who failed MTX and switched to infliximab.     

Guselkumab,an anti‐interleukin‐23 monoclonal antibody,for the treatment of moderate to severe plaque‐type psoriasis in Japanese patients: Efficacy and safety results from a phase 3, randomized,double‐blind,placebo‐controlled study

Previous global studies of guselkumab have demonstrated clinical benefits in patients with psoriasis. The aim of this 52‐week, phase 3 study was to evaluate efficacy and safety of guselkumab in Japanese patients with moderate to severe plaque‐type psoriasis. Patients randomly received guselkumab 50 mg or 100 mg at weeks 0, 4 and every 8 weeks, or placebo with cross‐over to guselkumab 50 mg or 100 mg at week 16. Co‐primary end‐points were the proportion of patients achieving Investigator's Global Assessment (IGA) cleared/minimal (0/1) and 90% or more improvement in Psoriasis Area and Severity Index (PASI‐90) at week 16. Overall, 192 patients were randomized to placebo, guselkumab 50 mg or 100 mg. At week 16, patients in the placebo group were crossed over to guselkumab 50 mg or 100 mg. At week 16, a significantly (P < 0.001) higher proportion of patients receiving guselkumab 50 mg and 100 mg versus placebo achieved IGA 0/1 (92.3% and 88.9% vs 7.8%) and PASI‐90 (70.8% and 69.8% vs 0%). Patients in guselkumab 50 mg and 100 mg groups achieved significant improvement versus placebo in PASI‐75 (89.2% and 84.1% vs 6.3%, P < 0.001) at week 16; improvement was maintained through week 52. Incidences of treatment‐emergent adverse events were comparable among the groups through week 16; the most commonly reported was nasopharyngitis. No new safety concerns were observed until week 52. In conclusion, guselkumab treatment demonstrated superior efficacy over placebo and was well tolerated in Japanese patients with moderate to severe plaque‐type psoriasis.     

A randomized trial of etanercept as monotherapy for psoriasis

OBJECTIVE: To determine safety and efficacy of monotherapy with etanercept. DESIGN: Randomized, double-blind, placebo-controlled, multicenter study. SETTING: Outpatient, ambulatory; private practice and university dermatology research centers. PATIENTS: Patients aged at least 18 years, with plaque psoriasis involving 10% or more of body surface area; 148 were screened and 112 were randomly assigned to treatment groups and received study drug. INTERVENTIONS: Patients received placebo or etanercept, 25 mg, subcutaneously twice a week for 24 weeks. Other psoriasis therapies were limited during the study. MAIN OUTCOME MEASURES: Safety measurements included tracking of adverse events and laboratory values. Efficacy was evaluated using the Psoriasis Area and Severity Index (PASI); the primary end point was a 75% improvement in PASI. Other efficacy measurements included patient and physician global assessments and quality-of-life measures. RESULTS: After 12 weeks of treatment, 17 (30%) of the 57 etanercept-treated patients and 1 (2%) of the 55 placebo-treated patients had achieved PASI 75%, and after 24 weeks, 32 (56%) of etanercept-treated patients and 3 (5%) of placebo-treated patients had reached this level (P<.001 for both time points). By 24 weeks, psoriasis was clear or minimal by physician's global assessment in more than 50% of patients who received etanercept. Treatment failure (PASI response <50) occurred in 23% of patients at week 24. All other measures confirmed the efficacy of etanercept. Adverse events were similar among etanercept and placebo groups. CONCLUSION: Etanercept monotherapy provided significant benefit to patients with psoriasis and had a favorable safety profile.     

An observational,prospective study of monthly adalimumab therapy for disease maintenance in psoriasis patients: a possible new therapeutic option for good responders to the initial induction treatment

Background While adalimumab is a mainstay of treatment for moderate to severe chronic plaque psoriasis, the data regarding optimal treatment intervals for therapeutic maintenance are limited. Objective We compared the clinical efficacy of biweekly maintenance administration of adalimumab with that of monthly treatment. Methods 17 psoriasis patients treated with adalimumab 40 mg every other week with initial loading dose of 80 mg until week 24 were assigned to the maintenance therapy with adalimumab 40 mg either every other week (n = 7), or every month (n = 10). The treatment efficacy was evaluated by the proportion of patients who achieved PASI 75 from the baseline at weeks 36, 48 and 60. There was no selection bias between the two groups. Results At week 24, all the patients except for one in each group achieved PASI 75. In both groups, all the patients who achieved PASI 75 at week 24 maintained PASI 75 responses at week 60. Regarding two patients who did not achieve PASI 75 at week 24, one biweekly treated patient experienced a gradual increase in therapeutic response while one monthly treated patient showed exacerbation after week 24. Conclusion Monthly adalimumab treatment seems to be a reasonable treatment option for patients who responded well to initial standard adalimumab treatment for 24 weeks. Since there are several limitations in this study, including the number of patients, observation period, and patients’ characteristics, large randomized controlled trials are needed to confirm these results.     

Efficacy and safety of risankizumab in Japanese patients with moderate to severe plaque psoriasis: Results from the SustaIMM phase 2/3 trial

Risankizumab, a humanized immunoglobulin G1 monoclonal antibody, selectively inhibits interleukin‐23, a key cytokine in the pathogenesis of psoriasis, by binding to its p19 subunit. In SustaIMM (ClinicalTrials.gov/NCT03000075), a phase 2/3, double‐blinded, placebo‐controlled study, Japanese patients with moderate to severe plaque psoriasis (n = 171) were stratified by bodyweight and concomitant psoriatic arthritis and randomized 2:2:1:1 to 75 mg risankizumab, 150 mg risankizumab, placebo with cross‐over to 75 mg risankizumab and placebo with cross‐over to 150 mg risankizumab. Dosing was at weeks 0, 4, 16, 28 and 40, with placebo cross‐over to risankizumab at week 16. The primary end‐point was 90% or more improvement from baseline in Psoriasis Area and Severity Index (PASI‐90) at week 16 for risankizumab versus placebo. Missing data were imputed as non‐response. All primary and psoriasis‐related secondary end‐points were met for both risankizumab doses (P < 0.001). At week 16, PASI‐90 responses were significantly higher in patients receiving 75 mg (76%) or 150 mg (75%) risankizumab versus placebo (2%). Corresponding response rates were 86%, 93% and 10% for static Physician Global Assessment (sPGA) score of clear/almost clear; 90%, 95% and 9% for PASI‐75; and 22%, 33% and 0% for PASI‐100, with significantly higher responses for both risankizumab doses versus placebo. Through week 52, PASI and sPGA responses increased or were maintained and treatment‐emergent adverse events were comparable across treatment groups. Both doses of risankizumab were superior to placebo in treating patients with moderate to severe plaque psoriasis. The safety profile was consistent with previous risankizumab trials, with no new or unexpected safety findings.     

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.     

Efficacy and safety of secukinumab in the treatment of moderate‐to‐severe plaque psoriasis: a randomized,double‐blind,placebo‐controlled phase II dose‐ranging study

Background Conventional systemic therapies for plaque psoriasis have not fully met the needs of patients, and although current biologic treatments are generally well tolerated, concerns exist with respect to long‐term safety. Interleukin (IL)‐17A is believed to be an important effector cytokine in the pathogenesis of psoriasis and is produced by Th17 cells, a class of helper T cells that act outside the established Th1/Th2 paradigm for regulation of innate and adaptive immunity. Objectives To assess the efficacy and safety of different doses of secukinumab, a fully human anti‐IL‐17A IgG1κ monoclonal antibody, in patients with moderate‐to‐severe plaque psoriasis. Methods Patients (n = 125) were randomized 1 : 1 : 1 : 1 : 1 to receive subcutaneous doses of placebo (n = 22) or secukinumab [1 × 25 mg (n = 29), 3 × 25 mg (n = 26), 3 × 75 mg (n = 21) or 3 × 150 mg (n = 27)] at weeks 0, 4 and 8. After the 12‐week treatment period, patients entered a follow‐up period of 24 weeks. The primary efficacy outcome was at least 75% improvement from baseline in the Psoriasis Area and Severity Index score (PASI 75); secondary outcomes included the Investigator’s Global Assessment (IGA) and PASI 90 and 50 response rates. Results After 12 weeks of treatment, secukinumab 3 × 150 mg and 3 × 75 mg resulted in significantly higher PASI 75 response rates vs. placebo (82% and 57% vs. 9%; P < 0·001 and P = 0·002, respectively). Higher PASI 75 response rates compared with placebo were maintained throughout the follow‐up period with these dosages [week 36, 26% (n = 7) and 19% (n = 4) vs. 4% (n = 1), respectively], with a gradual decline of PASI 75 response over time after the dosing period. IGA response rates were significantly higher in the 3 × 150 mg group vs. placebo at week 12 (48% vs. 9%; P = 0·005) and were consistently higher for the 3 × 150 mg and 3 × 75 mg groups vs. placebo at all time points from week 4 onward. The PASI 90 response rate was significantly higher in the 3 × 150 mg group vs. placebo (52% vs. 5%) at week 12 and remained higher during the follow‐up period. Secukinumab was well tolerated. Two cases of neutropenia (≤ grade 2) were reported in the 3 × 150 mg cohort. Conclusions Treatment with subcutaneous secukinumab 3 × 75 mg and 3 × 150 mg met the primary outcome of PASI 75 response achievement after 12 weeks, demonstrating efficacy in moderate‐to‐severe psoriasis.     

A global phase III randomized controlled trial of etanercept in psoriasis: safety, efficacy, and effect of dose reduction

BACKGROUND: In previous studies, etanercept significantly improved plaque psoriasis and was well tolerated. OBJECTIVES: To examine further the efficacy and safety of etanercept and to assess maintenance of treatment effect after dose reduction of etanercept. METHODS: In this multicentre 24-week study in the U.S.A., Canada and Western Europe, patients were at least 18 years old; had active, clinically stable plaque psoriasis involving at least 10% of body surface area; had a minimum Psoriasis Area and Severity Index (PASI) of 10 at screening; and had received or were a candidate to receive systemic psoriasis therapy or phototherapy. During the first 12 weeks of the study, patients were randomly assigned to receive by subcutaneous injection etanercept twice weekly (BIW) at a dose of 50 mg or 25 mg, or placebo BIW in a double-blind fashion. During the second 12 weeks, all patients received etanercept 25 mg BIW. The primary endpoint was a 75% or greater improvement from baseline in PASI (PASI 75) at 12 weeks. RESULTS: Five hundred and eighty-three subjects were randomized and received at least one dose of study drug. At week 12, a PASI 75 was achieved by 49% of patients in the etanercept 50 mg BIW group, 34% in the 25 mg BIW group, and 3% in the placebo group (P < 0.0001 for each etanercept group compared with placebo). At week 24 (after 12 weeks of open-label 25 mg etanercept BIW), a PASI 75 was achieved by 54% of patients whose dose was reduced from 50 mg BIW to 25 mg BIW, by 45% of patients in the continuous 25 mg BIW group, and by 28% in the group that received placebo followed by etanercept 25 mg BIW. Etanercept was well tolerated throughout the study. CONCLUSIONS: Etanercept provided clinically meaningful benefit to patients with chronic plaque psoriasis, with no apparent decrease in efficacy after dose reduction.     

Apremilast,an oral phosphodiesterase 4 inhibitor,in the treatment of Japanese patients with moderate to severe plaque psoriasis: Efficacy,safety and tolerability results from a phase 2b randomized controlled trial

Apremilast, an oral, small‐molecule phosphodiesterase 4 inhibitor, works intracellularly within immune cells to regulate inflammatory mediators. This phase 2b randomized, placebo‐controlled study evaluated efficacy and safety of apremilast among Japanese patients with moderate to severe plaque psoriasis. In total, 254 patients were randomized to placebo, apremilast 20 mg b.i.d. (apremilast 20) or apremilast 30 mg b.i.d. (apremilast 30) through week 16; thereafter, all placebo patients were re‐randomized to apremilast 20 or 30 through week 68. Efficacy assessments included achievement of 75% or more reduction from baseline in Psoriasis Area and Severity Index score (PASI‐75; primary) and achievement of static Physician Global Assessment (sPGA; secondary) score of 0 (clear) or 1 (minimal) at week 16. Safety was assessed through week 68. At week 16, PASI‐75 response rates were 7.1% (placebo), 23.5% (apremilast 20; P = 0.0032 vs placebo) and 28.2% (apremilast 30; P = 0.0003 vs placebo); sPGA response rates (score of 0 or 1) were 8.8% (placebo), 23.9% (apremilast 20; P = 0.0165 vs placebo) and 29.6% (apremilast 30; P = 0.0020 vs placebo). Responses were maintained with apremilast through week 68. Most common adverse events (AEs) with placebo, apremilast 20 and apremilast 30 (0–16 weeks) were nasopharyngitis (8.3%, 11.8%, 11.8%), diarrhea (1.2%, 8.2%, 9.4%), and abdominal discomfort (1.2%, 1.2%, 7.1%), respectively. Exposure‐adjusted incidence of these AEs did not increase with continued apremilast treatment (up to 68 weeks). Apremilast demonstrated efficacy and safety in Japanese patients with moderate to severe plaque psoriasis through 68 weeks that was generally consistent with prior studies.     

A randomized, double-blind, placebo-controlled study to evaluate the addition of methotrexate to etanercept in patients with moderate to severe plaque psoriasis

Background Etanercept plus methotrexate combination therapy has not been adequately investigated in psoriasis. Objectives To evaluate etanercept plus methotrexate vs. etanercept monotherapy in patients with moderate to severe plaque psoriasis who had not failed prior methotrexate or tumour necrosis factor‐inhibitor therapy. Methods Patients received etanercept 50 mg twice weekly for 12 weeks followed by 50 mg once weekly for 12 weeks and were randomized 1 : 1 to receive methotrexate (7·5–15 mg weekly) or placebo. The primary endpoint was the proportion of patients achieving ≥75% improvement in Psoriasis Area and Severity Index (PASI 75) at week 24. Results In total, 239 patients were enrolled in each arm. PASI 75 was significantly higher at week 24 for the combination therapy group compared with the monotherapy group (77·3% vs. 60·3%; P < 0·0001). Other PASI improvement scores at week 12 [PASI 75, 70·2% vs. 54·3% (P = 0·01); PASI 50, 92·4% vs. 83·8% (P = 0·01); and PASI 90, 34·0% vs. 23·1% (P = 0·03)] showed similar results as did week 24 PASI 50 (91·6% vs. 84·6%; P = 0·01) and PASI 90 (53·8% vs. 34·2%; P = 0·01). Significantly more patients receiving combination therapy than monotherapy had static Physician’s Global Assessment of clear/almost clear at week 12 (65·5% vs. 47·0%; P = 0·01) and week 24 (71·8% vs. 54·3%; P = 0·01). Adverse events (AEs) were reported in 74·9% and 59·8% of combination therapy and monotherapy groups, respectively; three serious AEs were reported in each arm. Conclusions Combination therapy with etanercept plus methotrexate had acceptable tolerability and increased efficacy compared with etanercept monotherapy in patients with moderate to severe psoriasis.     

阿达木单抗治疗斑块型银屑病疗效及代谢综合征对疗效的影响

目的：明确阿达木单抗治疗斑块型银屑病患者的疗效。方法：收集2020年9月至2021年3月经阿达木单抗治疗的斑块型银屑病患者,分析经阿达木单抗治疗0、4、8、12周的PASI评分变化及相关性。结果：共收集20例患者,其中1例中断治疗,19例患者中伴和不伴代谢综合征患者分别为11例和8例。经阿达木单抗治疗12周后,19例患者PASI评分自基线时的9.7（2.0,15.6）下降到3.3（0.4,4.2）。伴代谢综合征患者中达到PASI 75/PASI 90患者分别为45%和0%,不伴代谢综合征患者分别为50%和50%。代谢综合征与疗效存在负相关性（r=-0.679,P＜0.01）。结论：阿达木单抗治疗斑块型银屑病有效,代谢综合征影响疗效。