A phase III, randomized, controlled trial of the fully human IL-12/23 mAb briakinumab in moderate-to-severe psoriasis

A previous phase II trial demonstrated that the fully human anti-IL-12/23 mAb briakinumab was efficacious in moderate-to-severe psoriasis. A subsequent 52-week, double-blind, placebo-controlled phase III study evaluated induction and maintenance treatment. Patients were randomized 2:1 to briakinumab (200?mg at weeks 0 and 4 and 100?mg at week 8) or placebo; those with physician's global assessment "clear" or "minimal" (PGA "clear/minimal") at week 12 were then re-randomized 2:2:1 to briakinumab 100 mg every 4 weeks (q4-wk), every 12 weeks (q12-wk), or to matching placebo to week 52. Primary analyses conducted by nonresponder imputation compared proportions achieving PGA "clear/minimal" (weeks 12 and 52) and ≥75% improvement in psoriasis area and severity index (PASI 75; week 12). In all, 76.0% of briakinumab vs. 4.3% of placebo-treated patients achieved PGA "clear/minimal," and 80.7% vs. 4.5%, respectively, achieved PASI 75 at week 12 (P<0.001 each). At week 52, 79.2% of q4-wk-treated patients achieved PGA "clear/minimal" compared with 41.6% and 6.0% of q12-wk and placebo-treated patients, respectively (P<0.001 for all treatment comparisons). Higher numbers of the following adverse events (AEs) of interest were observed with briakinumab during the placebo-controlled period, suggesting the need for surveillance for these events: serious infections (five vs. one event with briakinumab vs. placebo, respectively), nonmelanoma skin cancers (NMSCs; four vs. zero squamous cell carcinomas (SCCs)), and major adverse cardiovascular events (MACEs; five vs. zero events).     

Guselkumab,a human interleukin‐23 monoclonal antibody in Japanese patients with generalized pustular psoriasis and erythrodermic psoriasis: Efficacy and safety analyses of a 52‐week,phase 3, multicenter,open‐label study

Generalized pustular psoriasis (GPP) and erythrodermic psoriasis (EP) are the rare and severe subtypes of psoriasis, which are often difficult to treat. The aim of this phase 3, open‐label study was to evaluate efficacy and safety of guselkumab, a human interleukin‐23 monoclonal antibody, in Japanese patients with GPP and EP. Guselkumab 50 mg was administrated to GPP (n = 10) and EP (n = 11) patients at weeks 0, 4 and thereafter every 8 weeks (q8w). Beginning at week 20, patients were escalated to 100 mg q8w if they met the dose escalation criteria. The primary end‐point was the proportion of patients achieving treatment success (Clinical Global Impression score of “very much improved”, “much improved” or “minimally improved”) at week 16. Safety evaluations included assessment of treatment‐emergent adverse events (TEAE) through week 52. At week 16, the proportions of GPP and EP patients achieving treatment success were 77.8% (7/9) and 90.9% (10/11), respectively. Furthermore, guselkumab treatment consistently showed improvement in responses of secondary end‐points such as Psoriasis Area and Severity Index, Investigator's Global Assessment, Japanese Dermatological Association severity index and improvement in body surface area involvement. Improvements in quality of life, as assessed by the Dermatology Life Quality Index, were also observed through week 52. The most commonly reported TEAE was nasopharyngitis (28.6%, 6/21). Safety findings were consistent with those observed previously in other studies. In conclusion, guselkumab treatment demonstrated efficacy and showed no safety concerns in Japanese patients with GPP and EP through week 52.     

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.     

Efficacy and safety results from a phase III, randomized controlled trial comparing the safety and efficacy of briakinumab with etanercept and placebo in patients with moderate to severe chronic plaque psoriasis

Background The tumour necrosis factor‐α antagonist etanercept and the interleukin (IL)‐12/23p40 antagonist ustekinumab have been shown to be effective psoriasis therapies. The IL‐12/23p40 antagonist briakinumab was shown to be effective psoriasis treatment in a phase II study. Objectives To assess the efficacy, safety and tolerability of briakinumab compared with etanercept and placebo in patients with moderate to severe psoriasis. Methods Three hundred and fifty patients were enrolled in this phase III, 12‐week study (M10‐315, NCT00710580) and randomized in the following 2:2:1 ratio: 139 patients received 200 mg briakinumab at weeks 0 and 4 followed by 100 mg briakinumab at week 8; 139 patients received 50 mg of etanercept twice weekly 3–4 days apart at weeks 0–11; 72 patients received placebo injections matching active treatment. 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, 72·7% achieved a PGA of 0/1 at week 12 as compared with 29·5% of etanercept‐treated patients and 4·2% of placebo‐treated patients (P < 0·001, for both comparisons). Of the briakinumab‐treated patients, 80·6% achieved a PASI 75 response at week 12 as compared with 39·6% of etanercept‐treated and 6·9% of placebo‐treated patients (P < 0·001, for both comparisons). Serious adverse events were reported in two (1·4%) briakinumab‐treated patients, one (0·7%) etanercept‐treated patient and two (2·8%) placebo‐treated patients. 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.     

Twenty‐four‐week interim analysis from a phase 3 open‐label trial of adalimumab in Japanese patients with moderate to severe hidradenitis suppurativa

Hidradenitis suppurativa (HS) is a chronic skin disease characterized by recurrent painful inflamed nodules/abscesses and draining fistulas that negatively impact quality of life. Adalimumab, a monoclonal antibody against tumor necrosis factor‐α, has been approved in the EU, USA and Japan for the treatment of moderate to severe HS. This is an interim analysis of an ongoing phase 3, multicenter, open‐label, single‐arm study of the safety and efficacy of adalimumab weekly dosing in Japanese patients with moderate to severe HS. Fifteen patients received adalimumab 160 mg at week 0, 80 mg at week 2 and 40 mg every week thereafter starting at week 4. The fulfillment of Hidradenitis Suppurativa Clinical Response was assessed under adalimumab treatment; clinical response was assessed by skin pain, total abscess and inflammatory nodule count and modified Sartorius score; and quality of life and safety were assessed. At week 12, 86.7% of patients achieved clinical response, with improvements at week 12 across the primary and secondary end points generally sustained through week 24. Adalimumab weekly dosing was generally safe and well tolerated with no new safety findings through week 24. These results suggest that adalimumab is effective and well tolerated in Japanese patients with moderate to severe HS.     

Tacrolimus 0.1% ointment in nail psoriasis: a randomized controlled open‐label study

Background Despite recent advances in the treatment of psoriasis, the therapeutic options for nail psoriasis are very limited, particularly when this is the only manifestation of the disease. Objective We performed a randomized controlled open‐label study to assess the efficacy and safety of a topical treatment with tacrolimus 0.1% ointment in nail psoriasis. Methods In each patient, tacrolimus 0.1% ointment was prescribed for application only on the affected nails of a randomly selected hand for 12 weeks, whereas nails of the other hand did not receive any treatment. Severity of nail psoriasis was evaluated using the Nail Psoriasis Severity Index (NAPSI) score. Results We enrolled 21 consecutive psoriatic patients. At week 12, a statistically significant (P < 0.001) improvement was obtained in the treated hands with respect to the hands used as control (NAPSI score absolute change 13.0 and 3.0 respectively). Each of the enrolled patients concluded the period of treatment, but one patient was withdrawn from tacrolimus application after 9 weeks because of the appearance of acute paronychia. Discussion Our study showed that tacrolimus 0.1% ointment may be an efficacious and safe therapeutic opportunity in the treatment of nail psoriasis. Our data should be confirmed by a double‐blind study with a larger sample of patients.     

Safety of efalizumab in adults with chronic moderate to severe plaque psoriasis: a phase IIIb, randomized, controlled trial

Background To provide safety data for efalizumab, a recombinant humanized monoclonal IgG₁ antibody, in adults with chronic plaque psoriasis. Methods A 12‐week, Phase IIIb, randomized, double‐blind, parallel‐group, placebo‐controlled trial. At 58 study sites in the USA and Canada, 686 patients with moderate to severe chronic plaque psoriasis received an initial conditioning dose of efalizumab 0.7 mg/kg subcutaneously (SC) followed by either 11 weekly doses of efalizumab 1 mg/kg SC or matching placebo. Main outcome measures were safety and tolerability outcomes (primary) and efficacy outcomes (secondary). Results During 12 weeks of therapy with efalizumab or placebo, the incidence of clinical adverse events was 82.2% and 72.9%, respectively; the incidence of serious adverse events was 1.8% and 3.4%, respectively; and the incidence of nonserious adverse events leading to withdrawal was 1.8% and 1.7%, respectively. In the efalizumab group, there were no clinically significant changes in vital signs or laboratory parameters and no evidence of end‐organ toxicities. A significantly higher proportion of patients receiving efalizumab than those receiving placebo achieved ≥ 75% improvement in the Psoriasis Area and Severity Index (PASI) (P < 0.001), ≥ 50% improvement in PASI (P < 0.001), and a static Physician's Global Assessment rating of Minimal or Clear (P < 0.001). The mean improvement in the Psoriasis Symptom Assessment was significantly greater in the efalizumab group (P < 0.001). Conclusions Efalizumab treatment SC for 12 weeks was safe, well tolerated, and effective in patients with moderate to severe chronic plaque psoriasis.