Combination therapy with adapalene-benzoyl peroxide and oral lymecycline in the treatment of moderate to severe acne vulgaris: a multicentre, randomized, double-blind controlled study

Background Oral antibiotics in association with a topical retinoid with or without benzoyl peroxide (BPO) are the recommended first‐line option in the treatment of moderate to severe acne vulgaris. Objectives To evaluate the efficacy and safety of oral lymecycline 300 mg with adapalene 0·1%–BPO 2·5% (A/BPO) fixed‐dose gel in comparison with oral lymecycline 300 mg with a vehicle gel in subjects with moderate to severe acne vulgaris. Methods A total of 378 subjects were randomized in a double‐blind, controlled trial to receive once‐daily lymecycline with either A/BPO or vehicle for 12 weeks. Evaluations included percentage changes from baseline in lesion counts, success rate (subjects ‘clear’ or ‘almost clear’), skin tolerability, adverse events and patients’ satisfaction. Results The median percentage reduction from baseline in total lesion counts at week 12 was significantly higher (P < 0·001) in the lymecycline with A/BPO group (?74·1%) than in the lymecycline with vehicle group (?56·8%). The success rate was significantly higher (47·6% vs. 33·7%, P = 0·002) in subjects treated with lymecycline and A/BPO. Both inflammatory and noninflammatory lesions were significantly reduced at week 12 (both P < 0·001) with a rapid onset of action from week 2 for noninflammatory lesions (P < 0·001) and week 4 for inflammatory lesions (P = 0·005). The A/BPO and lymecycline combination was well tolerated. The proportion of satisfied and very satisfied subjects was similar in both groups, but the number in the A/BPO group who were ‘very satisfied’ was significantly greater (P = 0·031). Conclusion These results demonstrate the clinical benefit of combining A/BPO with lymecycline in the treatment of moderate to severe acne vulgaris.     

Daily treatment with adapalene gel 0.1% maintains initial improvement of acne vulgaris previously treated with oral lymecycline

Topical retinoids are often recommended for preventing acne recurrence, but there are relatively few well-controlled maintenance studies published. The objective of the present study was to assess the maintenance effect of adapalene gel 0.1% relative to gel vehicle in subjects successfully treated in a previous 12-week adapalene-lymecycline 300 mg combination therapy study. This was a multicentre, investigator-blind, randomised, controlled study in 19 European centres. A total of 136 subjects with moderate to moderately-severe acne vulgaris who showed at least moderate improvement from baseline when treated with either adapalene plus lymecycline or lymecycline plus gel vehicle in a previous 12 week study were included. Subjects were randomised to receive adapalene gel 0.1% or vehicle once-daily for 12 weeks. Efficacy and safety criteria included maintenance rate, percent reduction in lesion counts (total, inflammatory, non inflammatory), global severity assessment, cutaneous tolerability, and adverse events. Adapalene provided better results relative to gel vehicle for all efficacy assessments. The maintenance rate for total lesions was 84.7% vs. 63.5% (P = 0.0049) with adapalene and the vehicle, respectively. Adapalene was safe and well tolerated in this study. This study demonstrates a clinical benefit of continued treatment with adapalene gel 0.1% as a maintenance therapy for acne.     

Lymecycline in the treatment of acne: an efficacious,safe and cost-effective alternative to minocycline

A comparison of efficacy, safety and cost-effectiveness of lymecycline and minocycline in the treatment of acne vulgaris has been addressed. This was a multicenter, randomized, investigator-masked, parallel group trial involving patients with moderate to moderately severe acne vulgaris, receiving either lymecycline or minocycline for 12 weeks. Efficacy and safety evaluation was performed at baseline and at weeks 4, 8, and 12 and completed by a pharmacoeconomic analysis including week 12 data. One hundred and thirty-six patients were enrolled. At week 12, the mean percent reductions in inflammatory count were 63 % and 65 %, and for total lesions counts 58 % and 56 % for lymecycline and for minocycline respectively. Median percent reduction in non-inflammatory count were 54 % and 47 % for lymecycline and for minocycline respectively. Eighty-seven per cent of all patients tolerated the treatments well. Treatment with lymecycline was found to be 4 times more cost-effective than with minocycline. Results showed that lymecycline has a comparable efficacy and safety profile to minocycline while being 4 times more cost-effective.     

Efficacy and safety of secukinumab in Taiwanese patients with moderate to severe plaque psoriasis: Subanalysis from ERASURE phase III study

The efficacy and safety of secukinumab, a fully human anti‐interleukin‐17A monoclonal antibody, has been evaluated for moderate to severe plaque psoriasis in global trials which have included a low proportion of Asian subjects. We analyzed the efficacy and safety of secukinumab in Taiwanese patients in a phase III global clinical trial (ERASURE). Fifty‐one Taiwanese patients were randomized into s.c. placebo, 150 and 300 mg secukinumab treatment groups. The proportions of patients who achieved 75% or more improvement in Psoriasis Area and Severity Index (PASI‐75) at week 12 were 87.5% with 300 mg secukinumab, 70% with 150 mg secukinumab, 0% with placebo. Of the patients receiving 300 mg secukinumab, 68.8% achieved PASI‐90 at week 12. Analysis of overall patients receiving 300 mg secukinumab for 12 weeks showed that the proportion of PASI‐75 responders was less in patients with body mass index of 25 or more than less than 25. During the entire 52 weeks, the incidence of adverse events (AE) was consistent with the overall population in ERASURE. The most common AE (cases/per 100 patient‐year) during the entire treatment period were upper respiratory tract infection and pruritus. The duration of upper respiratory tract infection per 100 patient‐year was approximately 399 days in placebo, 1261 days in 150 mg secukinumab and 1805 days in 300 mg secukinumab. The safety and efficacy of secukinumab in Taiwanese patients was compatible with the global phase III study in the treatment of moderate to severe plaque psoriasis.     

Adapalene 0.1%/Benzoyl Peroxide 2.5% Gel

Adapalene 0.1%/benzoyl peroxide 2.5% gel (Epiduo?, Tactuo?) is the only fixed-dose combination product available that combines a topical retinoid with benzoyl peroxide; it targets three of the four main pathophysiologic factors in acne. This article reviews the therapeutic efficacy and tolerability of topical adapalene 0.1%/benzoyl peroxide 2.5% gel in the treatment of patients aged ≥ 12 years with acne vulgaris, as well as summarizing its pharmacologic properties. In three 12-week trials in patients aged ≥12 years with moderate acne, success rates were significantly higher with adapalene 0.1%/benzoyl peroxide 2.5% gel than with adapalene 0.1% gel or benzoyl peroxide 2.5% gel alone, and combination therapy had an earlier onset of action. In addition, significantly greater reductions in total, inflammatory, and noninflammatory lesion counts were seen in patients receiving adapalene 0.1%/benzoyl peroxide 2.5% gel than in those receiving adapalene 0.1% gel or benzoyl peroxide 2.5% gel alone. Adapalene 0.1%/benzoyl peroxide 2.5% gel did not significantly differ from clindamycin 1%/benzoyl peroxide 5% gel in terms of the reduction in the inflammatory, noninflammatory, or total lesion counts in patients with mild to moderate acne, according to the results of a 12-week trial. Twelve-week studies showed that topical adapalene 0.1%/benzoyl peroxide 2.5% gel in combination with oral lymecycline was more effective than oral lymecycline alone in patients with moderate to severe acne, and topical adapalene 0.1%/benzoyl peroxide 2.5% gel in combination with oral doxycycline hyclate was more effective than oral doxycycline hyclate alone in patients with severe acne. In patients with severe acne who responded to 12 weeks’ therapy with topical adapalene 0.1%/benzoyl peroxide 2.5% gel plus oral doxycycline hyclate or oral doxycycline hyclate alone, an additional 6 months’ therapy with adapalene 0.1%/benzoyl peroxide 2.5% gel was more effective than vehicle gel at maintaining response, with further improvement seen in adapalene 0.1%/benzoyl peroxide 2.5% gel recipients. A noncomparative study also demonstrated the efficacy of 12 months’ therapy with adapalene 0.1%/benzoyl peroxide 2.5% gel in patients with acne vulgaris. Topical adapalene 0.1%/benzoyl peroxide 2.5% gel was generally well tolerated in patients with acne. In 12-week trials, the most commonly occurring treatment-related adverse events included erythema, scaling, dryness, and stinging/burning; these dermatologic treatment-related adverse events were usually of mild to moderate severity, occurred early in the course of treatment, and resolved without residual effects. Topical adapalene 0.1%/benzoyl peroxide 2.5% gel was generally well tolerated in the longer term, with dry skin being the most commonly occurring treatment-related adverse event over 12 months of treatment. In conclusion, adapalene 0.1%/benzoyl peroxide 2.5% gel is a valuable agent for the first-line treatment of acne vulgaris.     

维胺酯和异维A酸治疗寻常痤疮随机双盲研究

目的 评价维胺酯胶囊和异维A酸胶丸治疗中重度寻常痤疮的疗效和安全性.方法 采用多中心、随机、双肓双模拟、对照临床研究,按痤疮综合分析系统(GAGS)评价痤疮的严重程度,将评分确定为中重度痤疮的患者随机分为维胺酯组(50mg,每日3次)和异维A酸组(10mg,每日2次),于服药前、服药后2、4、6周计数皮损,观察疗效和不良反应.结果 共入组227例,计入全分析集(FAS)分析213例,符合方案集(PPS)分析200例.PPS分析治疗后2、4、6周异维A酸组有效率分别为6.0%、29.0%、57.0%;维胺酯组分别为5.0%、20.0%、51.00%,两组比较差异无统计学意义(P>0.05).各随访期皮损数下降值比较,除异维A酸组炎性丘疹和脓疱数下降值高于维胺酯组(P<0.05)外,粉刺、结节类皮损数两组差异无统计学意义.FAS分析不良反应发生率异维A酸组(68.81%)显著高于维胺酯组(36.53%)(P<0.001),常见不良反应如口干、口唇脱屑异维A酸组发生率显著高于维胺酯组(P<0.001),不良反应的程度也明显重于维胺酯组(P<0.05).结论 异维A酸和维胺酯治疗中重度痤疮疗效较为一致,但异维A酸治疗炎性皮疹起效较快,同时其常见不良反应也多于维胺酯.     

Lymecycline and minocycline in inflammatory acne: a randomized, double-blind intent-to-treat study on clinical and in vivo antibacterial efficacy

BACKGROUND: Some antibiotics represent a mainstay in acne treatment. However, studies comparing their efficacies are rare. AIM: To evaluate the clinical and in vivo antibacterial effect of lymecycline and minocycline at different dosages. METHOD: Eighty-six patients with moderate to severe acne were enrolled in a randomized, double-blind, intent-to-treat study comparing in three parallel groups the effect of (1) lymecycline 300 mg daily for 12 weeks, (2) minocycline 50 mg daily for 12 weeks and (3) minocycline 100 mg daily for 4 weeks followed by 50 mg daily for 8 weeks. Evaluations were made at the screening visit and at five on-treatment visits. They consisted of clinical counts of acne lesions and evaluations of bacterial viability using dual flow cytometry performed on microorganisms collected from sebaceous infundibula by cyanoacrylate strippings. RESULTS: Patients receiving minocycline 100/50 mg had the best clinical outcome, particularly in the reduction of the number of papules. By the end of the trial, the microbial response to minocycline 100/ 50 mg was also superior to either of the other two treatments. There were less live and more dead bacteria. CONCLUSION: In this trial, minocycline 100/50 mg was superior for the treatment of inflammatory acne when compared to lymecycline 300 mg and minocycline 50 mg.     

Topical methyl aminolaevulinate photodynamic therapy for treatment of facial acne vulgaris: results of a randomized, controlled study

BACKGROUND: There is a need for alternative treatments for moderate to severe acne vulgaris. Preliminary experience suggests that topical methyl aminolaevulinate photodynamic therapy (MAL-PDT) may have potential. OBJECTIVES: To investigate the efficacy and tolerability of MAL-PDT for treatment of moderate inflammatory facial acne. PATIENTS/METHODS: Thirty patients aged 15-28 years with moderate to severe acne were included in a blinded, prospective, randomized, placebo-controlled multicentre study. Each side of each patient's face was randomly assigned to treatment with MAL (160 mg g1) or placebo cream, applied for 3 h prior to illumination. A second treatment was given 2 weeks later. On each occasion, patients assessed the intensity of pain using a 10-cm visual analogue scale. Inflammatory and noninflammatory acne lesions were counted at baseline and 4 and 10 weeks after the last PDT treatment. The investigator assessed the global severity of acne at baseline (seven patients had severe acne on at least one side of the face) and each study visit using a six-point rating scale. Data were analysed on an intention-to-treat basis, including all 30 patients. RESULTS: There was a statistically significant greater reduction in the total inflammatory lesion count with MAL-PDT compared with placebo PDT at week 12; median reduction 54% [95% confidence interval (CI) 35-64%] vs. 20% (95% CI 8-50%), P = 0.0006. MAL-PDT was associated with more pain than placebo PDT, although intensity varied across centres and was reduced with repeated treatment. Local adverse events were consistent with this treatment modality. CONCLUSIONS: MAL-PDT is effective in the treatment of moderate to severe inflammatory facial acne. Further studies are warranted to optimize this promising procedure.     

Efficacy and safety of apremilast in subjects with moderate to severe plaque psoriasis: results from a phase II,multicenter, randomized,double‐blind,placebo‐controlled,parallel‐group,dose‐comparison study

Background Apremilast, a small molecule specific inhibitor of phosphodiesterase 4, works intracellularly to modulate pro‐inflammatory and anti‐inflammatory mediator production. Objective Assess apremilast efficacy and safety in moderate to severe plaque psoriasis. Methods Phase II, 12‐week, multicenter, double‐blind, placebo‐controlled, parallel‐group, dose‐comparison study of 259 subjects randomized 1 : 1 : 1 to placebo, apremilast 20 mg QD or apremilast 20 mg BID. Results More subjects receiving apremilast 20 mg BID achieved ≥ 75% reduction in Psoriasis Area and Severity Index (PASI‐75) vs. placebo (24.4% vs. 10.3%; P = 0.023). A similar proportion of subjects receiving apremilast 20 mg QD and placebo achieved PASI‐75 at week 12 [9/87 (10.3%, each group)]. Mean per cent reduction in PASI from baseline was 17.4% for placebo, 30.3% for apremilast 20 mg QD (P = 0.021 vs. placebo) and 52.1% for apremilast 20 mg BID (P < 0.001). Apremilast 20 mg BID significantly decreased mean body surface area involvement vs. placebo (30.8% vs. 3.2%; P < 0.001). The most common adverse events were headache, nasopharyngitis, diarrhoea and nausea. Most events (> 90%) were mild to moderate and did not lead to study discontinuation. Serious adverse events occurred in four placebo subjects (panic attack, hospitalization for rehabilitation, hospitalization for alcoholism, worsening psoriasis), one receiving apremilast 20 mg QD (knee surgery) and in one receiving apremilast 20 mg BID (worsening psoriasis). The panic attack was considered treatment‐related; both cases of worsening psoriasis occurred after medication discontinuation. No deaths or opportunistic infections were reported. Conclusion Apremilast 20 mg BID for 12 weeks was effective and well tolerated in subjects with moderate to severe plaque psoriasis.     

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.     

5-氨基酮戊酸光动力疗法治疗痤疮

目的 探索5-氨基酮戊酸光动力疗法（ALA-PDT）治疗中、重度痤疮的安全性及有效性。方法 将70例中、重度痤疮患者随机分为两组。治疗组35例,给予ALA-PDT治疗,每2周治疗1次,共治疗1 ~ 3次;对照组35例,口服异维A酸胶囊治疗,共服用6周。在治疗第2、4、6周对两组患者进行疗效判断和比较。结果 35例接受ALA-PDT治疗的患者经过1 ~ 3次治疗后（第2、4、6周）,总有效率达97.1%;对照组于6周时总有效率为80.0%,治疗组疗效明显优于对照组（P < 0.05）。另外,ALA-PDT组复发程度明显轻于对照组,且病情控制时间明显延长。ALA-PDT组有个别患者局部出现暂时性色素沉着,但无瘢痕发生。结论 ALA-PDT是一种简单、高效、不良反应轻微的治疗中、重度痤疮的新疗法。     

Twelve‐week,multicenter, placebo‐controlled,randomized, double‐blind,parallel‐group,comparative phase II/III study of benzoyl peroxide gel in patients with acne vulgaris: A secondary publication

A placebo‐controlled, randomized, double‐blind, parallel‐group, comparative, multicenter study was conducted to investigate the efficacy and safety of benzoyl peroxide (BPO) gel, administrated once daily for 12 weeks to Japanese patients with acne vulgaris. Efficacy was evaluated by counting all inflammatory and non‐inflammatory lesions. Safety was evaluated based on adverse events, local skin tolerability scores and laboratory test values. All 609 subjects were randomly assigned to receive the study products (2.5% and 5% BPO and placebo), and 607 subjects were included in the full analysis set, 544 in the per protocol set and 609 in the safety analyses. The median rates of reduction from baseline to the last evaluation of the inflammatory lesion counts, the primary end‐point, in the 2.5% and 5% BPO groups were 72.7% and 75.0%, respectively, and were significantly higher than that in the placebo group (41.7%). No deaths or other serious adverse events were observed. The incidences of adverse events in the 2.5% and 5% BPO groups were 56.4% and 58.8%, respectively; a higher incidence than in the placebo group, but there was no obvious difference between the 2.5% and 5% BPO groups. All adverse events were mild or moderate in severity. Most adverse events did not lead to study product discontinuation. The results suggested that both 2.5% and 5% BPO are useful for the treatment of acne vulgaris.     

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.     

Successful treatment of moderate to severe plaque psoriasis with the PEGylated Fab' certolizumab pegol: results of a phase II randomized, placebo-controlled trial with a re-treatment extension

Background Certolizumab pegol (CZP) is a PEGylated antitumour necrosis factor agent. Objectives To evaluate the efficacy and safety of CZP in patients with plaque psoriasis. Methods In a randomized, placebo‐controlled, double‐blind study, 176 patients with moderate to severe psoriasis received placebo or CZP 400 mg at week 0 followed by placebo or CZP (200 or 400 mg) every other week until week 10. Co‐primary endpoints were ≥ 75% improvement from baseline in Psoriasis Area and Severity Index (PASI 75) and a Physician’s Global Assessment (PGA) of clear‐almost clear at week 12. A re‐treatment extension study was conducted in 71 CZP PASI 75 responders who relapsed during a 12‐ to 24‐week observation period without treatment. Results PASI 75 was achieved by 44/59 (75%), 48/58 (83%) and 4/59 (7%) patients in the CZP 200 mg, CZP 400 mg and placebo groups, respectively (P < 0·001 for both treatment arms vs. placebo). A PGA score of clear‐almost clear was achieved by 53%, 72% and 2%, respectively (P < 0·001 for both treatment arms vs. placebo). In the re‐treatment study median PASI scores were similar at week 12 in the first treatment and re‐treatment periods for both CZP groups. Serious adverse events occurred in 3%, 5% and 2% of CZP 200 mg, CZP 400 mg and placebo patients, respectively. Conclusions Treatment with CZP significantly improved psoriasis at week 12. Similar efficacy was observed at week 12 in patients receiving re‐treatment for loss of response after drug withdrawal.     

Clinical evaluation of the efficacy and safety of fractional bipolar radiofrequency for the treatment of moderate to severe acne scars

Several treatment modalities are used for the treatment of acne scars with variable results. Recent studies showed that fractional radiofrequency may be an effective treatment modality for acne scars. The objective of this study was to assess the efficacy, safety, tolerability and patient satisfaction of fractional bipolar radiofrequency (RF), the eTwo? system (Syneron Candela Ltd., Yokneam, Israel) for treating acne scars. Twelve patients with moderate to severe acne scars received 3–5 treatments with the Sublative fractionated bipolar RF applicator of the eTwo device at 1‐month intervals. Patients were evaluated clinically and photographically at each visit and 3 months after the final treatment. Very good improvement (at least one scale) was seen after completing the five treatments. The patient satisfaction survey (Global Aesthetic Improvement Scale scores) revealed that half (6 out of 12) of the patients reported to be satisfied with treatment results, while the other half reported to be very satisfied. Beyond the expected erythema and minimal scab formation in the treated areas, which was mild and transient, none of the participants reported any adverse events. The data presented here support the high efficacy and safety of fractionated bipolar RF for the aesthetic improvement of moderate to severe acne scars.     

A network meta‐analysis for the comparison of efficacy and safety of interleukin (IL)‐23 targeted drugs in the treatment of moderate to severe psoriasis

A variety of interleukin‐23 targeted drugs have been used to treat moderate to severe psoriasis, but it is not clear which is most effective. This network meta‐analysis compared and summarized the short‐term efficacy and safety of interleukin‐23 (IL‐23) targeted drugs in the treatment of moderate to severe psoriasis. PubMed, Embase, Web of Science, and Cochrane Library were used to search randomized controlled trials (RCTs) about the treatment of moderate to severe psoriasis with ustekinumab (Ust), guselkumab (Gus), tildrakizumab (Til), and risankizumab (Ris). Bayesian Network Meta‐analysis (NMA) was used to calculate Psoriasis Area and Severity Index 75%, 90%; Physician Global Assessment score of 0 or 1 (PGA 0/1); Dermatology Life Quality Index of 0 or 1 (DLQI 0/1), and safety (adverse events [AEs]) effect estimates (odds ratio OR) and 95% confidence intervals. Direct, indirect, and network meta‐analysis estimates were calculated using a random‐effects model. The GRADE method was used to assess the quality of evidence for each pair‐wise comparison. In addition, the surface under the cumulative ranking curve (SUCRA) analysis was used to rank the treatment level for each outcome indicator. This network meta‐analysis included 14 RCTs with 8402 patients. The results indicate that the curative effect of the IL‐23 targeted drugs is better than that of a placebo. Network meta‐analysis showed that Ris90 mg and Ris180 mg were significantly more effective than Til (5, 25, 100, and 200 mg), Ust (45 mg, 90 mg, body weight‐based administration), Gus 100 mg and Ris (75 and 150 mg). Regarding safety, there is no significant difference in the risk of adverse events between drugs targeting IL‐23 and placebo. In addition, according to the ranking of SUCRA, Ris 90 mg has the best efficacy index for PASI 75 and PGA 0/1, with SUCRA values of 97.6% and 97.1%, respectively. Ris 180 mg ranked first in PASI 90 (91.1%), while Ris 75 mg performed best in DLQI 0/1 (73.7%). In this network meta‐analysis, risankizumab showed the best curative effect in the short‐term treatment of moderate to severe psoriasis, and the risk of adverse events was not significantly different from placebo. However, more research data are needed for further study in the field of cost to evaluate which drug strikes the most favorable balance among efficacy, safety, and cost of access.     

Metformin as an adjunct therapy for the treatment of moderate to severe acne vulgaris: A randomized open‐labeled study

Insulin, insulin‐like growth factor‐1 (IGF‐1) and essential amino acids activate the mechanistic target of rapamycin complex 1 (mTORC1), the main nutrient‐sensitive kinase. Metformin, through inhibition of mTORC1 may improve acne. A 12‐week, randomized, open‐labeled study evaluated the efficacy and safety of metformin as an adjunct for moderate to severe facial acne. In total, 84 patients received either oral tetracycline 250 mg bd and topical benzoyl peroxide 2.5% with or without metformin 850 mg daily. Evaluations constituted lesion counts, the Cardiff Acne Disability Index (CADI), metabolic parameters and treatment success rate (Investigators Global Assessment score of 0 or 1 or improvement of two grades). Treatment success rates were higher in the metformin group (66.7% vs. 43.2%; p = .04). The mean percentage reduction from baseline in total lesion counts at Week 12 was greater in the metformin group (71.4% vs. 65.3%; p = .278). The CADI scores showed a greater mean reduction in the metformin group (4.82 vs. 4.22; p = .451). Metformin was equally efficacious in improving acne in lean and overweight subjects. Gastrointestinal symptoms were noted in 31.7% of subjects on metformin. This study presents favorable data for metformin as an adjunct for acne treatment. Further randomized placebo‐controlled studies are required.     

Efficacy and safety results from the randomized controlled comparative study of adalimumab vs. methotrexate vs. placebo in patients with psoriasis (CHAMPION)

BACKGROUND: Biologic therapies such as adalimumab, a tumour necrosis factor antagonist, are safe and effective in the treatment of moderate to severe chronic plaque psoriasis. OBJECTIVES: To compare a biologic agent with methotrexate, a traditional systemic agent, to define clearly the role of biologics in psoriasis. METHODS: Patients with moderate to severe plaque psoriasis were randomized to adalimumab (80 mg subcutaneously at week 0, then 40 mg every other week, n=108), methotrexate (7.5 mg orally, increased as needed and as tolerated to 25 mg weekly; n=110) or placebo (n=53) for 16 weeks. The primary efficacy endpoint was the proportion of patients achieving at least a 75% improvement in the Psoriasis Area and Severity Index (PASI 75) after 16 weeks. Safety was assessed at all visits through week 16. RESULTS: After 16 weeks, 79.6% of adalimumab-treated patients achieved PASI 75, compared with 35.5% for methotrexate (P<0.001 vs. adalimumab) and 18.9% for placebo (P<0.001 vs. adalimumab). Statistically significantly more adalimumab-treated patients (16.7%) than methotrexate-treated patients (7.3%) or placebo-treated patients (1.9%) achieved complete clearance of disease. The response to adalimumab was rapid, with a 57% improvement in mean PASI observed at week 4. Adverse events were similar across treatment groups. Adverse events leading to study discontinuation were greatest in the methotrexate group, primarily because of hepatic-related adverse events. CONCLUSIONS: After 16 weeks, adalimumab demonstrated significantly superior efficacy and more rapid improvements in psoriasis compared with either methotrexate or placebo.     

Efficacy and safety of tofacitinib, an oral Janus kinase inhibitor, in the treatment of psoriasis: a Phase 2b randomized placebo-controlled dose-ranging study

Background Tofacitinib is a novel, oral Janus kinase inhibitor under investigation as a potential treatment for plaque psoriasis. Objectives This Phase 2b, 12‐week, dose‐ranging study (A3921047, NCT00678210) aimed to characterize the exposure–response, efficacy and safety of tofacitinib vs. placebo in patients with moderate‐to‐severe chronic plaque psoriasis. Methods One hundred and ninety‐seven patients were randomized. The primary endpoint was the proportion of patients achieving a ≥ 75% reduction in the Psoriasis Area and Severity Index (PASI 75) score at week 12. Results At week 12, PASI 75 response rates were significantly higher for all tofacitinib twice‐daily groups: 25·0% (2 mg; P < 0·001), 40·8% (5 mg; P < 0·0001) and 66·7% (15 mg; P < 0·0001), compared with placebo (2·0%). Significant increases in the proportion of PASI 75 responses were seen by week 4 and were maintained at week 12. Exposure–response over the 0–15 mg tofacitinib twice‐daily dose range was successfully characterized. PASI 50, PASI 90 and Physician’s Global Assessment response rates were also higher for tofacitinib vs. placebo. The most frequently reported adverse events (AEs) were infections and infestations: 22·4% (2 mg twice daily), 20·4% (5 mg twice daily), 36·7% (15 mg twice daily) and 32·0% (placebo). Discontinuations due to AEs were 6·0%, 2·0%, 4·1% and 6·1% of patients in the placebo, and 2, 5 and 15 mg twice‐daily tofacitinib groups, respectively. Dose‐dependent increases from baseline in mean serum high‐density lipoprotein, low‐density lipoprotein and total cholesterol, and decreases in haemoglobin and neutrophils were observed. Conclusion Short‐term treatment with oral tofacitinib results in significant clinical improvement in patients with moderate‐to‐severe plaque psoriasis and is generally well tolerated.