Infliximab for the treatment of psoriasis in Greece: 4 years of clinical experience at a single centre

Background Infliximab, a chimeric monoclonal antibody, has been shown to be effective for moderate to severe psoriasis. Clinical experience with long‐term infliximab therapy for psoriasis is accumulating, and it is therefore important to share our experience with its use in real‐life clinical practice. Objectives To report our experience with infliximab (Remicade^®; Schering Plough, Kenilworth, NJ, U.S.A.) for the treatment of moderate to severe plaque psoriasis (and/or arthritis) from a single clinic in Greece. Patients and methods Between August 2004 and March 2008, 62 patients presenting to our clinic with moderate to severe psoriasis were treated with infliximab. Disease phenotype, clinical course, disease severity and adverse events were assessed throughout the treatment period. Results Infliximab resulted in a reduction of median Psoriasis Area and Severity Index (PASI) of 70% at week 6 and 84·4% at week 14. Nineteen patients who have completed 1 year on infliximab treatment experienced sustained efficacy with a median PASI improvement of 92·16% and a Physician’s Global Assessment (PGA) of ‘clear’ or ‘almost clear’, while nine patients have reached approximately 20 months of continuous therapy. All patients with psoriatic arthritis showed marked improvement in their clinical symptoms following the first infusion. Eight patients (12·9%) experienced adverse events that required discontinuation of treatment. There were no statistically significant differences in PASI and Dermatology Life Quality Index (DLQI) scores between patients with arthritis and those with only skin lesions, or between those who received methotrexate, either from the beginning or during infliximab therapy, and those who did not receive methotrexate at all. Selected patients of interest are discussed. Conclusions The above data confirm previous reports that treatment with infliximab is an efficacious and safe option for patients with moderate to severe plaque psoriasis (and/or arthritis). Long‐term follow‐up, continued pharmacovigilance, and controlled comparative studies will be required to fully evaluate its use in the treatment of psoriasis.     

Algorithm to select optimal systemic anti‐psoriatic drugs in relation with patients' Psoriasis Area and Severity Index score for plaque psoriasis

This study sought to develop a therapeutic algorithm for selecting the optimal systemic drugs to treat moderate to severe psoriasis, based on the patient's Psoriasis Area Severity Index (PASI) score. Data from 191 patients undergoing treatment for plaque psoriasis were retrospectively analyzed. Pre‐ and post‐treatment PASI scores were compared across patients treated with acitretin of retinoic acid (RA; n = 95), methotrexate (MTX; n = 41) or cyclosporin A (CsA; n = 55). The PASI score improvement was examined at weeks 4 (primary end‐point) and 12 (secondary end‐point). MTX and CsA had a higher global therapeutic efficacy, with more patients exhibiting a marked improvement (≥75% improvement in PASI [PASI 75]) at week 12 with MTX (56.1%, P = 0.028) and CsA (54.5%, P = 0.025) than RA (35.8%). Multivariate analysis adjusting for confounders produced consistent results (P = 0.026). For patients with severe psoriasis (PASI >12), the PASI 75 response was higher with CsA (55.6%) than RA (31.5%) (P = 0.023) at week 4 and higher with MTX (57.1%, P = 0.029) and CsA (61.5%, P = 0.017) than RA (21.7%) at week 12. Because RA is a standard systemic drug, the RA group was divided into two subgroups based on the PASI 50 response at week 12. Marked or moderate improvement (PASI ≥50) with RA was observed in patients with a pretreatment PASI score less than 14. Thus, oral RA is recommended as a first‐line drug for patients with PASI of less than 14, and MTX or CsA are recommended for patients with PASI of 14 or more.     

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.     

Infliximab treatment results in significant improvement in the quality of life of patients with severe psoriasis: a double-blind placebo-controlled trial

Background Psoriasis is a chronic disease that significantly diminishes the health‐related quality of life (HRQOL). Infliximab is a chimeric, tumour necrosis factor α monoclonal antibody that has been shown to improve the signs and symptoms of plaque psoriasis. Objectives The objective of this study was to evaluate the effect of infliximab induction therapy on the HRQOL of patients with severe plaque psoriasis. Methods In this double‐blind, placebo‐controlled trial, 249 patients were randomly assigned to receive intravenous infusions of 3 or 5 mg kg^?1 of infliximab or placebo and were treated at weeks 0, 2 and 6. Patients completed the Dermatology Life Quality Index (DLQI) at baseline and week 10. Results Infliximab induction therapy resulted in a substantial improvement in HRQOL. At week 10, patients in the infliximab 3‐ and 5‐mg kg^?1 groups showed a median percentage improvement in DLQI scores of 84·0% and 91·0%, respectively, compared with 0% in the placebo group (P < 0·001). The median decrease from baseline in DLQI score at week 10 was 8·0 and 10·0 for the 3 and 5 mg kg^?1 infliximab groups, respectively, compared with 0 in the placebo group (P < 0·001). Thirty‐three per cent and 40% of patients in the 3 and 5 mg kg^?1 infliximab groups, respectively, had a DLQI score of 0 at week 10, compared with 2% in the placebo group (P < 0·001). There was a strong correlation between the percentage change from baseline at week 10 in Psoriasis Area and Severity Index (PASI) scores and the percentage change in DLQI scores during the same period (Spearman's correlation, 0·61, P < 0·001). When the infliximab and placebo treatment groups were combined, patients with at least 75% improvement in PASI scores between baseline and week 10 had a greater mean improvement in DLQI scores (81%) than those with 50–75% improvement in PASI during the same period (60%). Conclusions Infliximab induction therapy resulted in significant improvement in HRQOL in patients with severe 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.     

Secukinumab improves psoriasis symptoms in patients with inadequate response to cyclosporine A: A prospective study to evaluate direct switch

There are limited data on the safety and efficacy of switching to secukinumab from cyclosporine A (CyA) in patients with psoriasis. The purpose of the present study was to assess the efficacy and safety of secukinumab for 16 weeks after direct switching from CyA in patients with moderate‐to‐severe psoriasis. In this multicenter, open‐label, phase IV study, 34 patients with moderate‐to‐severe psoriasis and inadequate response to CyA received secukinumab 300 mg s.c. at baseline and weeks 1, 2, 3, 4, 8 and 12. The primary end‐point was ≥75% improvement from baseline in Psoriasis Area and Severity Index score (PASI 75) at week 16. The efficacy of secukinumab treatment was evaluated up to week 16, and adverse events (AE) were monitored during the study. The primary end‐point of the PASI 75 response at week 16 was achieved by 82.4% (n = 28) of patients receiving secukinumab. Early improvements were observed with secukinumab, with PASI 50 response of 41.2% at week 2 and PASI 75 response of 44.1% at week 4. AE were observed in 70.6% (n = 24) of patients, and there were no serious AE or deaths reported in the entire study period. Secukinumab showed a favorable safety profile consistent with previous data with no new or unexpected safety signals. The results of the present study show that secukinumab is effective in patients with psoriasis enabling a smooth and safe direct switch from CyA to biological therapy.     

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.     

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.     

Treatment of plaque‐type psoriasis with oral CF101: data from an exploratory randomized phase 2 clinical trial

Aims CF101 demonstrated a marked anti‐inflammatory effect in Phase 2 studies conducted in patients with rheumatoid arthritis and dry eye syndrome. The aim of this study was to evaluate the safety and efficacy of CF101 for the treatment of patients with moderate to severe plaque‐type psoriasis. Materials and methods This was a phase 2, multicentre, randomized, double‐blind, dose‐ranging, placebo‐controlled study. Seventy five patients with moderate to severe plaque‐type psoriasis were enrolled, randomized and treated with CF101 (1, 2, or 4 mg) or placebo administered orally twice daily for 12 weeks. Safety and change from base line of Psoriasis Area and Severity Index (PASI) score and physician’s global assessment (PGA) score over 12 weeks. Results In the 2 mg CF101‐treated group, a progressive improvement in the mean change from baseline in the PASI score vs. placebo throughout the study period was observed, with a statistically significant difference on weeks 8 and 12 (P = 0.047; P = 0.031, respectively). In this group, 35.3% of the patients achieved PASI ≥50 response, and 23.5% of the patients achieved a PGA score of 0 or 1. CF101 was safe and well tolerated. Conclusions CF101 was well tolerated and demonstrated clear evidence of efficacy in patients with moderate to severe plaque psoriasis.     

Efficacy and safety of mycophenolate mofetil vs. methotrexate for the treatment of chronic plaque psoriasis

Background Methotrexate (MTX) is a well‐known systemic drug for moderate to severe chronic plaque psoriasis. Recently, mycophenolate mofetil (MMF) has been recommended for psoriasis. Objective To compare the efficacy and safety of MMF vs. MTX for the treatment of chronic plaque psoriasis. Methods Thirty‐eight consecutive patients with Psoriasis Area and Severity Index (PASI) >10 were randomly assigned for 12 weeks of treatment with either MTX (18 patients; initial dose, 7.5 mg/week) or MMF (20 patients; dose; 2 g/day) and were followed for 12 weeks after discontinuing the treatment. The differences between the two groups were analysed at the end of treatment and follow‐up comparing with baseline values. Results After 12 weeks of treatment, the mean ± SD score for the PASI decreased from 16.46 ± 5.29 at baseline to 3.17 ± 2.35 among 15 patients treated with MTX, whereas the score decreased from 17.43 ± 7.42 to 3.97 ± 5.95 among 17 patients treated with MMF (P > 0.05). Twelve weeks after discontinuing the treatment, the scores were 4.77 ± 3.52 and 5.94 ± 4.27, respectively (P > 0.05). PASI ‐75 were achieved in 58.8% of patients in MMF group and 73.3% in MTX group (P > 0.05). Three months after discontinuing the treatment, PASI‐75 remained in 33.3% of patients in MMF and 53.3% of MTX group (P > 0.05). Both drugs were well tolerated and side‐effects were minor and transient. Conclusions No significant differences in efficacy were found between MTX and MMF groups. MMF may represent a good alternative for the treatment of psoriasis in patients who are unable to take MTX or other available drugs due to contraindication or toxicity.     

Five‐year experience with infliximab: Follow up of the product familiarisation program

This 5‐year retrospective analysis is of 22 patients who participated in the product familiarisation program (PFP) at St Vincent's Hospital Melbourne, prior to the listing of infliximab on the Pharmaceutical Benefit Scheme. Criteria for inclusion were being an adult with chronic plaque psoriasis, having a psoriasis area and severity index (PASI) score of at least 15 with an inadequate response or intolerance to three of the following: phototherapy, acitretin, cyclosporin and methotrexate. Participants were infused with infliximab 5 mg/kg on the standard induction (weeks 0, 2 and 6) and maintenance (8‐weekly) protocols. At each visit PASI and dermatology life quality index (DLQI) scores were recorded. Success was determined as the proportion of patients achieving at least a 75% improvement in the PASI score from baseline (PASI 75). At 60 months after commencement of therapy, 31% of patients remained on infliximab. Those who did retained PASI 75 with a DLQI of 0 or 1. Of those who ceased infliximab, nine did so due to loss of efficacy, three for personal reasons, two for serious adverse events and one was lost to follow up. Adverse events included non‐melanoma skin cancers, infections and abnormal liver enzymes. Infliximab in the Australian context has proven to be a highly effective treatment of chronic plaque psoriasis, and patients who remained on the drug derived a high level of satisfaction, assessed both subjectively (DLQI) and objectively (PASI 75). The variable response indicates that psoriasis is a heterogeneous disease and investigation into potential patient selection for treatment in the future is warranted.     

Combining etanercept and acitretin in the therapy of chronic plaque psoriasis: a 24-week, randomized, controlled, investigator-blinded pilot trial

Background Combination treatments may increase efficacy while reducing dosages and side‐effects of individual agents. No randomized controlled trials have been published combining biologics with conventional agents for psoriasis. Objectives To investigate the efficacy and safety of the association of acitretin and etanercept in the treatment of moderate to severe chronic plaque psoriasis. Methods A 24‐week, randomized, controlled, investigator‐blinded pilot trial was conducted. Sixty adult patients with moderate to severe chronic plaque psoriasis were randomized into three groups to receive etanercept 25 mg twice weekly subcutaneously, oral acitretin 0·4 mg kg^?1 daily or etanercept 25 mg once weekly plus acitretin 0·4 mg kg^?1 daily. The primary end point was a 75% or greater improvement in Psoriasis Area and Severity Index (PASI) from baseline (PASI 75) at week 24. Results At week 24, PASI 75 response was achieved by 10 of 22 patients in the etanercept group (45%), six of 20 in the acitretin group (30%) and eight of 18 (44%) in the group treated with etanercept plus acitretin (P = 0·001 for both etanercept groups compared with acitretin alone). A 50% or greater improvement from baseline in PASI was achieved by 15 of 22 (68%), 10 of 20 (50%) and 12 of 18 (67%) patients, respectively (P = 0·001). The safety profiles of the three groups were similar. Conclusions A combined therapeutic regimen with etanercept 25 mg once weekly and acitretin 0·4 mg kg^?1 daily is as effective as etanercept 25 mg twice weekly, and more effective than acitretin alone. Although larger studies are needed to confirm these results, the etanercept/acitretin association could offer several advantages in the therapy of moderate to severe chronic plaque psoriasis.     

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.     

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.     

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.     

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.     

Treatment of palmoplantar psoriasis with infliximab: a randomized,double‐blind placebo‐controlled study

Background Palmoplantar psoriasis is a difficult to treat variant of plaque psoriasis. Objective To study the safety and efficacy of infliximab in non‐pustular palmoplantar psoriasis. Methods Patients with non‐pustular palmoplantar psoriasis affecting at least 10% of their palms and soles and with a modified palmoplantar psoriasis area and severity index (m‐PPPASI) of at least eight were recruited. Patients were randomized (1:1) to receive infliximab 5 mg/kg or placebo at weeks 0, 2 and 6. Patients initially randomized to placebo received infliximab at weeks 14, 16 and 20 whereas patients randomized to infliximab received additional infliximab infusions every 8 weeks until week 22. Results Twenty four (24) patients were randomized in this study. At week 14, 33.3% and 66.7% of patients treated with infliximab achieved m‐PPPASI 75 and m‐PPPASI 50 respectively compared to 8.3% for both m‐PPPASI 75 (P = 0.317) and m‐PPPASI 50 (P = 0.009) for patients randomized to placebo. A reduction of 50.3% in the mean surface area of palms and soles affected with psoriasis was seen at week 14 in patients randomized to infliximab as compared to an increase of 14.9% in patients randomized to placebo (P = 0.009). Conclusions This pilot study did not reach its primary endpoint of m‐PPPASI 75 at week 14. However, infliximab was observed to be more efficacious than placebo in improving PPSA and with respect to the percentage of patients reaching m‐PPPASI 50 at week 14. Larger and longer term studies are needed for severe patients to better assess the efficacy of infliximab in palmoplantar psoriasis.     

Efficacy and safety of ixekizumab treatment for Japanese patients with moderate to severe plaque psoriasis,erythrodermic psoriasis and generalized pustular psoriasis: Results from a 52‐week,open‐label,phase 3 study (UNCOVER‐J)

Psoriasis, a chronic, immune‐mediated skin disease characterized by red, scaly plaques, affects approximately 0.3% of the population in Japan. The aim of this open‐label study was to evaluate the long‐term efficacy and safety of ixekizumab, a humanized, anti‐interleukin‐17A monoclonal antibody, in Japanese patients with plaque psoriasis (n = 78, including 11 psoriatic arthritis), erythrodermic psoriasis (n = 8) and generalized pustular psoriasis (n = 5). Ixekizumab was administrated s.c. at baseline (week 0, 160 mg), from weeks 2 to 12 (80 mg every 2 weeks), and from weeks 16 to 52 (80 mg every 4 weeks). At week 52, 92.3% of patients with plaque psoriasis achieved Psoriasis Area and Severity Index (PASI) 75, 80.8% achieved PASI 90, 48.7% achieved PASI 100, and 52.6% had remission of plaques (by static Physician Global Assessment, sPGA [0]). Difficult to treat areas of psoriasis (nail or scalp) also responded to ixekizumab. All patients with psoriatic arthritis who were assessed (5/5) achieved an American College of Rheumatology 20 response. Most patients with erythrodermic psoriasis or generalized pustular psoriasis responded to ixekizumab and the clinical outcome was maintained over 52 weeks (75% and 60% of patients achieved sPGA [0, 1] at week 52, respectively). Mostly mild or moderate treatment‐emergent adverse events were reported by 79 of 91 patients; the most common were nasopharyngitis, eczema, seborrheic dermatitis, urticaria and injection site reactions. In conclusion, 52‐week ixekizumab treatment was efficacious and well tolerated in Japanese patients with plaque psoriasis. Efficacy was also observed in patients with erythrodermic psoriasis, generalized pustular psoriasis and psoriatic arthritis.     

Oral tofacitinib efficacy,safety and tolerability in Japanese patients with moderate to severe plaque psoriasis and psoriatic arthritis: A randomized,double‐blind,phase 3 study

Tofacitinib is an oral Janus kinase inhibitor that is being investigated for psoriasis and psoriatic arthritis. Japanese patients aged 20 years or more with moderate to severe plaque psoriasis and/or psoriatic arthritis were double‐blindly randomized 1:1 to tofacitinib 5 or 10 mg b.i.d. for 16 weeks, open‐label 10 mg b.i.d. for 4 weeks, then variable 5 or 10 mg b.i.d. to Week 52. Primary end‐points at Week 16 were the proportion of patients achieving at least a 75% reduction in Psoriasis Area and Severity Index (PASI75) and Physician's Global Assessment of “clear” or “almost clear” (PGA response) for psoriasis, and 20% or more improvement in American College of Rheumatology criteria (ACR20) for patients with psoriatic arthritis. Safety was assessed throughout. Eighty‐seven patients met eligibility criteria for moderate to severe plaque psoriasis (5 mg b.i.d., n = 43; 10 mg b.i.d., n = 44), 12 met eligibility criteria for psoriatic arthritis (5 mg b.i.d., n = 4; 10 mg b.i.d., n = 8) including five who met both criteria (10 mg b.i.d.). At Week 16, 62.8% and 72.7% of patients achieved PASI75 with tofacitinib 5 and 10 mg b.i.d., respectively; 67.4% and 68.2% achieved PGA responses; all patients with psoriatic arthritis achieved ACR20. Responses were maintained through Week 52. Adverse events occurred in 83% of patients through Week 52, including four (4.3%) serious adverse events and three (3.2%) serious infections (all herpes zoster). No malignancies, cardiovascular events or deaths occurred. Tofacitinib (both doses) demonstrated efficacy in patients with moderate to severe plaque psoriasis and/or psoriatic arthritis through 52 weeks; safety findings were generally consistent with prior studies.     

Efficacy and safety of briakinumab vs. etanercept and placebo in patients with moderate to severe chronic plaque psoriasis

Background The anti‐interleukin‐12/23p40 monoclonal antibody briakinumab has been shown in a phase II study to be effective psoriasis treatment. Objectives The aim of the current study was to assess the efficacy, safety and tolerability of briakinumab compared with etanercept and placebo in patients with moderate to severe chronic plaque psoriasis. Methods In this phase III, 12‐week study (M10‐114, NCT00691964), 347 patients were randomized in a 2 : 2 : 1 ratio to receive 200 mg briakinumab at weeks 0 and 4 followed by 100 mg briakinumab at week 8 (n = 138); 50 mg of etanercept twice weekly 3–4 days apart at weeks 0–11 (n = 141); or placebo injections matching active treatment (n = 68). The co ‐ primary efficacy endpoints were the proportion of patients achieving a Physician’s Global Assessment (PGA) of 0/1 at week 12, and the proportion of patients achieving a Psoriasis Area and Severity Index (PASI) 75 response at week 12. Results Of the briakinumab‐treated patients, 71·0% achieved a PGA of 0/1 at week 12 as compared with 39·7% of etanercept‐treated patients and 2·9% of placebo‐treated patients, (P < 0·001, for both comparisons). Of the briakinumab‐treated patients 81·9% achieved a PASI 75 response at week 12 as compared with 56·0% of etanercept‐treated and 7·4% of placebo‐treated patients (P < 0·001, for both comparisons). Serious adverse event rates were reported in four (2·9%) patients receiving briakinumab, one (0·7%) patient receiving etanercept and one (1·5%) placebo‐treated patient. Conclusions In patients with moderate to severe psoriasis, briakinumab had superior efficacy to both placebo and etanercept at 12 weeks as administered in this study.