Effectiveness of anti‐interleukin 23 biologic drugs in psoriasis patients who failed anti‐interleukin 17 regimens. A real‐life experience

Among the most recent biologic drugs available for psoriasis therapy, those targeting interleukin‐17 (secukinumab and ixekizumab) or its receptor (brodalumab) have been shown to be quickly effective. However, in those patients who failed one or more of the above‐cited drugs, real‐life data on the effectiveness of switching to one anti‐interleukin‐23 biologic (guselkumab, risankizumab, or tildrakizumab) are very scarce. Here, we report our experience in treating 12 multi‐failure psoriatic patients, prospectively followed‐up over 6 months, who showed a significant improvement in their psoriasis after switching from an anti‐interleukn‐17 to an anti‐interleukin‐23 drug.     

A case of erythrodermic psoriasis successfully treated with guselkumab

Erythrodermic psoriasis (EP) is the most severe form of psoriasis, resulting in significant morbidity and mortality. EP treatment with biologics is not well ruled by international guidelines, so most biological drugs are used basing on case reports or small case series. Guselkumab, a fully human anti‐interleukin (IL)‐23 monoclonal antibody, is approved for moderate to severe plaque psoriasis while its use in EP is off label. To date, no case reports on Caucasian patients have been described in the literature. We report the case of 38‐year‐old Caucasian male with EP successfully treated with guselkumab, reaching PASI 100 after 20 weeks of therapy and still maintaining this response at Week 48. Our case report suggests guselkumab as an efficacious and well‐tolerated treatment in EP, presenting a long‐term efficacy in the prevention of recurrences. Further studies are warrant to confirm our data, with controlled trials specifically dedicated to EP being strictly needed in order to verify the role and efficacy of anti‐IL23 in EP.     

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.     

Consistent responses with guselkumab treatment in Asian and non‐Asian patients with psoriasis: An analysis from VOYAGE 1 and VOYAGE 2

Guselkumab, an interleukin‐23 blocker, was superior to placebo and adalimumab and well‐tolerated in phase 3 psoriasis studies (VOYAGE 1 and VOYAGE 2). This analysis evaluated the consistency of response in the Asian subpopulation in VOYAGE 1 and VOYAGE 2. Study designs were identical through week 24; patients were randomized to guselkumab, placebo, or adalimumab. Investigator's Global Assessment (IGA), Psoriasis Area and Severity Index (PASI), safety, and pharmacokinetic and immunogenicity data from VOYAGE 1 and VOYAGE 2 were pooled and compared by race (Asian, n = 199; non‐Asian, n = 1630). At week 16, treatment differences between guselkumab and placebo were 78.2 (95% confidence interval [CI], 66.9–89.6) and 76.4 (95% CI, 72.7–80.2) percentage points for IGA 0/1 (score of 0 or 1) and 70.1 (95% CI, 60.0–80.1) and 68.5 (95% CI, 64.9–72.2) percentage points for PASI 90 (≥90% improvement) in the Asian and non‐Asian populations, respectively. Treatment differences between guselkumab and adalimumab were 31.1 (95% CI, 17.7–44.6) and 16.1 (95% CI, 11.2–21.0) percentage points for IGA 0/1 and 24.9 (95% CI, 9.4–40.5) and 23.2 (95% CI, 17.7–28.6) percentage points for PASI 90 in the Asian and non‐Asian populations, respectively. Similar results were observed at week 24. Safety was generally similar between populations and among treatment groups. Median serum guselkumab concentrations over time were comparable between the populations. Comparable responses between the Asian and non‐Asian populations in this analysis suggest that the overall efficacy, safety, and the resulting benefit/risk analyses from VOYAGE 1 and VOYAGE 2 are applicable to Asian populations.     

Clinical efficacy and safety of certolizumab pegol in cutaneous symptoms on psoriasis in patients with psoriatic arthritis: A retrospective analysis in real life

We present the results on retrospective analysis about the efficacy of Certolizumab pegol (CZP), an antitumor necrosis factor‐alpha agent, as monotherapy on skin psoriasis (PsO) in patients affect both by psoriatic arthritis (PsA) and mild‐severe PsO. To date, the CZP is authorized for the treatment of PsA, PsO beyond that rheumatoid arthritis, axial spondyloarthritis/ankylosing spondylitis, and Crohn's. Assessments included an evaluation of the Psoriasis Area and Severity Index (PASI). Twelve patients (9M and 3F mean age 57.8 ± 8 years) were enrolled in our study. Nine patients had been previously treated with others biologic agents, three patients were naïve. Clinical and laboratory evaluations including PASI, erythrosedimentation rate, and C‐reactive protein were performed at baseline (BL), at Week 12 (W12), Week 24 (W24), and Week 52 (W52) of treatment. Although the combination between methotrexate and CZP is allowed, we included, in our study, patients treated only with CZP. In such a way as to be as specific as possible, topical corticosteroids, vitamin D derivatives, retinoid creams, anthralin derivatives as well as p‐UVA or UV‐B have been forbidden to enrolled patients. With the same purpose, all the patients used the identical moisturizing cream two times a day. Mean PASI score decreased from 18 (BL) to 0 (W52) as follows: 18 at BL, 4 at W12, 0 at W24, and 0 at W52. Severe adverse events were not reported. Safety evaluations were performed every 3 months: liver and renal functions were monitored in all patients during the treatment, and no patient presented abnormal values. To the best of our knowledge, this is the first report that highlights the efficacy of CZP as monotherapy in psoriasis with mild to severe cutaneous involvement. Although to date the drug is authorized only for PsA, our results demonstrate that CZP is safe and effective on both cutaneous and joint components representing, therefore, an effective option in the treatment of cutaneous symptoms of PsO. Limitations of our study are presented by the relatively short observation time (W52) and by numeric small study group. Long‐term data with a larger number of enrolled patients are necessary in order to confirm our preliminary observations.     

When IL‐17 inhibitors fail: Real‐life evidence to switch from secukinumab to adalimumab or ustekinumab

Psoriasis is a chronic, systemic inflammatory disease that in the moderate to severe forms may benefit of biologics, namely TNF and IL‐12/23 and IL‐17 inhibitors. Loss of response, lack of response, or discontinuation due to adverse events represent a concrete therapeutic challenge for dermatologists that have to switch patients to other treatments. Although some evidences already exist toward the switch from IL‐12/23 and TNF inhibitors to IL‐17 inhibitors, conversely nothing is present toward the switch from IL‐17 inhibitors to IL‐12/23 and TNF inhibitors. We performed a real‐life study enrolling 50 patients randomly switched to adalimuamb, a TNF inhibitor, or ustekinumab, an IL‐12/23 inhibitor. Our observational study suggests that switching from IL‐17i to TNFi and IL‐12/23i is a safe and effective therapeutic strategy.     

Efficacy and safety of secukinumab in patients with generalized pustular psoriasis: A 52‐week analysis from phase III open‐label multicenter Japanese study

Generalized pustular psoriasis (GPP) is a severe inflammatory skin disease characterized by the presence of sterile pustules covering almost the entire body and systemic symptoms such as fever. Secukinumab, a fully human‐recombinant anti‐interleukin‐17A monoclonal antibody was indicated for psoriasis vulgaris and psoriatic arthritis in Japan but is not yet investigated for GPP. In this phase III, open‐label multicenter single arm study, the efficacy and safety of secukinumab as monotherapy or with co‐medication was evaluated in 12 Japanese patients with GPP. All the patients received secukinumab 150 mg s.c. at baseline, week 1, 2, 3 and 4, and then every 4 weeks. Two non‐responders were up‐titrated to 300 mg. Change in GPP severity from baseline was evaluated by clinical global impression (CGI) categorized as “worsened”, “no change”, “minimally improved”, “much improved” or “very much improved”. Treatment success was achieved by 83.3% (n = 10) of patients at week 16 (primary end‐point) with CGI evaluated as “very much improved” (n = 9) and “much improved” (n = 1). Moreover, the area of erythema with pustules improved as early as week 1 and resolved by week 16 in most of the patients. The improvements were sustained throughout 52 weeks. Over the 52‐week treatment period, secukinumab was well tolerated with no unexpected safety signals. Nasopharyngitis, urticaria, diabetes mellitus and arthralgia were the frequent adverse events reported. The data from this study shows that secukinumab can become one of the potent treatment options for GPP.     

Clinical predictors of nonresponse to anti‐TNF‐α agents in psoriatic patients: A retrospective study

Although the heterogeneity of the therapeutic response to TNF‐α blockers seems to be mainly due to genetic factors, several studies showed that a range of factors may influence it. The aim of our study was to investigate the impact of patients' demographic and clinical characteristics on primary response to an anti‐TNF‐α therapy in psoriatic patients. We retrospectively examined the relationship between various clinical and demographic features and response to treatment with etanercept, adalimumab, and infliximab, evaluated as PASI75 and average PASI improvement at weeks 12, 16, and 14, respectively. We analyzed data obtained from 199 patients. A better response to the treatment was significantly associated with male gender (OR = 2.59), coexistence of psoriatic arthritis (OR = 1.97), and PASI ≤15 at baseline (OR = 0.91). The present study supports that some clinical factors may be potential predictors of response to anti‐TNF‐α agents in psoriatic patients.     

Adalimumab in severe plaque psoriasis of childhood: A multi‐center,retrospective real‐life study up to 52 weeks observation

The objective of this study is to determine drug effectiveness and safety of the tumor necrosis factor‐alpha blocker monoclonal antibody adalimumab in a real‐life cohort of 54 children and/or adolescents with severe plaque psoriasis. Retrospective, multicenter analysis over a 52‐week period is discussed in this study. Efficacy was determined by the percentage of patients achieving Psoriasis Area Severity Index (PASI 75) and PASI 90 at weeks 16, 24, and 52 and the response in biologic‐naïve versus non‐naïve patients. Safety was assessed by the number of patients experiencing at least one adverse event. At week 16, 29.6% of patients achieved a 90% PASI score reduction (PASI 90), while 55.5% of patients achieved a 75% PASI score reduction (PASI 75). Effectiveness was sustained through week 24, since PASI 90 response increased to 55.5% and PASI 75 response increased to 74.0% of patients. The PASI response rates did not differ between biologic‐naïve and non‐naïve patients. The drug was well tolerated and no serious infections were observed. Adalimumab was effective and safe in this cohort of children with severe plaque psoriasis in a 52‐week observation. Effectiveness did not differ between biologic‐naïve and non‐naïve patients.     

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.     

Successful treatment with interleukin‐17A antagonists of generalized pustular psoriasis in patients without IL36RN mutations

Generalized pustular psoriasis (GPP) is a potentially life‐threatening disease that can be attributed to mutations in IL36RN in a subgroup of patients. In small trials, interleukin (IL)‐17A and IL‐17RA antagonists have been shown to be effective in patients with generalized pustular psoriasis in Japan. We identified seven patients who received the IL‐17A antagonists secukinumab (six cases) or ixekizumab (one case) in two dermatological centers. All patients showed a good or excellent clinical response. Anti‐IL‐17A therapy was well tolerated and ongoing in all patients after an average therapy duration of 12.9 months. Analysis of IL36RN mutation status was performed in six patients, one patient carried a heterozygous mutation, while the other five patients did not show a mutation in IL36RN. This is the first report of a successful treatment of GPP patients without IL36RN mutations responding to anti‐IL‐17A therapy.     

Efficacy and safety of fumaric acid esters in the long‐term treatment of psoriasis – A retrospective study (FUTURE)

Background: This study collected data on the safety and efficacy of fumaric acid esters (FAE; Fumaderm^®) in the long‐term treatment of psoriasis. Patients and Methods: Patients were included at 163 dermatological centers if they either had been treated continuously with FAE for at least 24 months, or for 36 months with interruptions of no longer than 6 months. Data were reported from baseline, after 3, 6, 12, 24, and 36 or more months of therapy. Safety parameters were monitored and the severity of skin symptoms was assessed by “Physician's Global Assessment” (PGA) and “Psoriasis Area and Severity Index” (PASI). Results: 984 patients were included with a mean duration of 44 months of continuous treatment. The percentage of patients documented as markedly improved or clear was 67 % after six months, 78 % after 24 months, and 82 % after 36 months of therapy. Improvement was similar in patients with moderate and severe disease. Changes of laboratory parameters were usually insignificant and did not require a modification of FAE treatment in more than 90 % of the cases. Conclusions: In the long‐term treatment of patients with moderate and severe psoriasis FAE show a good and sustained clinical efficacy combined with a favorable safety profile.     

SF‐36 healty survey on psoriasis quality‐of‐life: A study of 414 Taiwanese patients

Psoriasis is a chronic debilitating disease that impairs patients' physical and social functioning. The assessment of health‐related quality of life (HRQoL) provides a comprehensive insight into the actual disease burden that are not captured by the traditional clinical parameters. The objective of this study is to identify factors that may impact patients' HRQoL. We conducted a cross‐sectional study, recruiting a total of 414 psoriasis vulgaris patients between January 2008 and December 2011. Our study found no significant correlation between disease severity or duration of psoriasis with HRQoL. Female patients have poorer HRQoL. Psoriatic arthritis, nail involvement, burning and itching sensation have a detrimental effect on HRQoL. This study highlighted that specific disease‐associated symptoms such as itching and burning sensation, nail involvement and/or concomitant arthritis were important factors that may impact patients' HRQoL devoid of clinical severity. Physicians should carefully consider these factors when treating psoriasis patients.     

Costs and quality of life in patients with moderate to severe plaque‐type psoriasis in Germany: A multi‐center study

Background: This study evaluated costs, disease severity and health‐related quality of life (QoL) in patients with moderate to severe plaque‐type psoriasis. Patients and Methods: Patients with a ‘psoriasis area and severity index’ (PASI) > 12 and/or a body surface area (BSA) > 10 were enrolled in dermatological practices and hospital outpatient departments (n = 184) and the total costs of illness generated during the last 12 months were retrospectively calculated. QoL was assessed using the SF‐36 and the DLQI. Participants were stratified into three subgroups according to the treatment received during the 1 year documentation period; a) patients without and b) patients with phototherapy or standard systemic therapy, and c) patients who had failed, were intolerant or had contraindications to at least two standard systemic therapies. The study was performed before biologics became available for the treatment of psoriasis in Germany. Results: Included patients had severe skin symptoms (mean PASI 18.2) and a highly impaired QoL (mean DLQI 10.6). Total annual costs amounted to € 6,709. Patients belonging to subgroup C had the most severe skin symptoms (mean PASI 22.2), the lowest QoL (mean DLQI 12.6), the highest hospitalization rate and largest loss of productivity.These patients produced the highest total costs of 8.831 €/y. Conclusions: Patients who cannot (or can no longer) be adequately managed with standard treatments are characterized by high disease activity, high costs and reduced QoL. Improved treatment options particularly for these patients are medically necessary and appear economically sensible.     

Comparative study of the efficacy and safety of secukinumab vs ixekizumab in moderate‐to‐severe psoriasis after 1 year of treatment: Real‐world practice

There are no studies which directly compare efficacy in Psoriasis Area and Severity Index (PASI) response of secukinumab and ixekizumab. The main aim of this study was to compare the efficacy and safety of both drugs used to treat moderate‐to‐severe psoriasis patients over 52 weeks. Secondary objectives were to identify which factors related to prior biologic treatment influenced their efficacy and analyze data obtained at 12 weeks. A retrospective observational study was carried out, in which a group of the first 59 patients treated with secukinumab after its commercialization, was compared with another group of the first 29 patients treated with ixekizumab. The PASI 75, 90, and 100 response obtained at 52 weeks was 64.4%, 49.2%, and 41.4% for secukinumab and 75.9%, 62.1%, and 41.4% for ixekizumab, respectively, with no statistically significant differences. Regarding previous biological treatment, both treatments showed a decrease in efficacy as the number of prior biologics increases. No differences were found between secukinumab and ixekizumab in bio‐naïve or bio‐experienced patients, with the exception of a higher PASI 75 response at week 52 for ixekizumab in those patients with two or more previous biologics (P = .039) Secukinumab and ixekizumab have demonstrated high efficacy and safety, with no statistically significant differences.     

Antinuclear antibodies associate with loss of response to antitumour necrosis factor‐α therapy in psoriasis: a retrospective,observational study

Background An increasing number of patients with severe psoriasis are failing to respond to antitumour necrosis factor (TNF)‐α therapy (etanercept, infliximab and adalimumab). Objectives We observed that many of these patients developed antinuclear antibodies (ANA) and antidouble‐stranded DNA (anti‐dsDNA) antibodies while on treatment prompting us to investigate whether their development is associated with anti‐TNF treatment failure. Methods All patients with psoriasis who had received anti‐TNF therapies were identified and their blood results and treatment histories were obtained from electronic patient records and case notes. Results A total of 97 patients had been treated with anti‐TNF agents (60 were on their first agent, 22 had been on and stopped one agent, nine had been on and stopped two agents and six had been on and stopped all three agents). ANA developed in 17% of patients on their first treatment, 54% of patients who had failed one treatment, 78% of patients who had failed two treatments and 83% of patients who had failed all three treatments. Anti‐dsDNA antibodies developed in 2%, 27%, 33% and 83% of patients from the same respective groups. Significantly, the antibodies developed before treatment had failed with all three agents and their development was not related to the total time that patients had been on anti‐TNF therapy. Conclusions This study suggests that the development of ANA and anti‐dsDNA antibodies on anti‐TNF treatment may act as a marker of forthcoming treatment failure. Large‐scale prospective studies are required to assess the importance of this observation.     

Effects of tumor necrosis factor‐α, interleukin‐23 and interleukin‐17A inhibitors on bodyweight and body mass index in patients with psoriasis

Treatment with tumor necrosis factor‐α inhibitors has been reported to cause weight gain in patients with psoriasis; however, limited information is available in terms of the effects of interleukin (IL)‐23 and IL‐17A inhibitors on bodyweight (BW) in patients with psoriasis. This study aimed to investigate the effects of infliximab, ustekinumab and secukinumab on BW and body mass index (BMI) in patients with psoriasis. We retrospectively examined changes in BW and BMI among patients treated with these biologics at our hospital. At baseline, no significant differences in BW and BMI were observed among the patients treated with infliximab (n = 18), ustekinumab (n = 30) or secukinumab (n = 20). After 7 months of the therapy, significant increases in mean BW (from 71.4 to 74.3 kg) and mean BMI (from 24.7 to 25.7) were observed in the patients treated with infliximab, whereas no significant changes were observed in those treated with ustekinumab (BW, from 70.3 to 70.1 kg; BMI, from 25.4 to 25.3) or secukinumab (BW, from 69.0 to 68.9 kg; BMI, from 25.2 to 25.2). There were no differences in the proportion of the patients who showed 75% or more improvement in the Psoriasis Area and Severity Index among the three groups. These results suggest that infliximab increases BW in the patients with psoriasis, whereas ustekinumab and secukinumab do not affect the BW in these patients.