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.     

Efalizumab

Efalizumab is a humanized monoclonal antibody that binds to CD11a, the alpha-subunit of lymphocyte function-associated antigen-1, and consequently inhibits T-cell activation. In randomized, double-blind, placebo-controlled trials, efalizumab 1.0 mg/kg, administered subcutaneously once weekly for 12 weeks, significantly reduced disease activity in patients with chronic, moderate-to-severe plaque psoriasis. Significantly more efalizumab recipients had a > or =75% decrease in the Psoriasis Area and Severity Index (PASI) score [22.4-38.9%] than placebo recipients (2.4-4.9%); an additional 12 weeks of treatment resulted in sustained or increased PASI responses. The efficacy of weekly subcutaneous efalizumab was maintained during 15 months of treatment. Efalizumab significantly improved health-related quality of life in patients with chronic plaque psoriasis, with significant improvements in all the Dermatology Life Quality Index domains. Efalizumab was generally well tolerated in patients with chronic, moderate-to-severe plaque psoriasis, with few serious adverse events or treatment withdrawals. The most common adverse events were headache, chills, myalgia, pain, and fever; these most often occurred within 2 days of administration of the drug, were most frequent after the first or second dose, and decreased in frequency over time.     

Efficacy of sirolimus (rapamycin) administered concomitantly with a subtherapeutic dose of cyclosporin in the treatment of severe psoriasis: a randomized controlled trial

BACKGROUND: The identification of a highly potent immunosuppressive/antiproliferative agent with an acceptable toxicity profile has long been a goal for the management of severe plaque psoriasis. OBJECTIVES: To investigate the efficacy and safety of sirolimus (Rapamune) for severe psoriasis when given alone or in association with cyclosporin. METHODS: In a randomized, double-blind, eight parallel group, pilot study in 24 out-patient centres in seven European countries, 150 patients, 18 years and older, with severe chronic plaque psoriasis were given sirolimus 0.5, 1.5 and 3.0 mg m(-2) daily for 8 weeks, either alone or in association with a subtherapeutic dose of cyclosporin (1.25 mg kg(-1) daily). Cyclosporin 5 mg kg(-1) daily was the positive control and cyclosporin 1.25 mg kg(-1) daily the negative control. The primary efficacy variable was the mean percentage reduction in Psoriasis Area and Severity Index (PASI). Safety assessments included monitoring of adverse events, clinical laboratory parameters and sirolimus/cyclosporin blood concentrations. RESULTS: The greatest mean percentage decreases in PASI were seen with cyclosporin 5.0 mg kg(-1) daily (70.5%) and with sirolimus 3.0 mg m(-2) daily + cyclosporin 1.25 mg kg(-1) daily (63.7%). Both groups demonstrated significantly better results than cyclosporin 1.25 mg kg(-1) daily (mean decrease 33.4%). Serum creatinine levels were significantly lower for groups with sirolimus alone and sirolimus plus reduced-dose cyclosporin when compared with cyclosporin 5.0 mg kg(-1) daily. Adverse events associated with sirolimus included thrombocytopenia (5%), hyperlipidaemia (9%), aphthous stomatitis (9%) and acne (13%), whereas adverse events associated with cyclosporin included hot flushes (12%), hyperlipidaemia (9%) and increased serum creatinine (9%). CONCLUSIONS: The concomitant administration of sirolimus with a subtherapeutic dose of cyclosporin in severe psoriasis may permit a reduction in their respective toxicities, notably cyclosporin-induced nephrotoxicity.     

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.     

Combining PUVA therapy with systemic immunosuppression to treat progressive diffuse morphoea

Cyclosporin and mycophenolate mofetil (MMF) are immunosuppressant agents now used frequently in the field of organ transplantation. More recently cyclosporin has been used for the treatment of a number of dermatological conditions, including severe psoriasis and eczema. Extensive diffuse morphoea is very difficult to treat. PUVA, UVA and a number of immunomodulating drugs have been used to attempt improvement but are most beneficial only in early disease. Combination treatments are often used in psoriasis, for example, but are not reported in morphoea. We present the case of a patient treated initially with cyclosporin and PUVA and subsequently with MMF and PUVA, with considerable improvement in his condition.     

(8) Comparison of psoriasis treated with cyclosporin alone or cyclosporin and clobetasol propionate

Cyclosporin A (CyA) in the low dosage of 3 mg/kg/day has been shown to clear psoriasis; however, the disease relapses soon after withdrawal of the drug. Immunological studies have demonstrated persistence of activated T helper (TH) cells within the epidermis after clearance of psoriatic plaques with cyclosporin but disappearance if clearance is achieved by the use of topical clobetasol propionate (CP). If the relapse is a result of resumption of function by epidermal-activated TH cells then combination therapy with CP and CyA should delay the rate of relapse.
Six patients with chronic plaque psoriasis were treated with CyA at a dose of 3 mg/kg/day for a period of 6 weeks; during the first 2 weeks CP was applied twice daily to the psoriatic plaques. A second group of six psoriatic patients was treated with cyclosporin alone. The psoriasis was scored at weekly intervals during treatment using the Psoriasis Area and Severity Index (PASI), and for 4 weeks after cessation of treatment.
Using CyA alone, the mean time taken to achieve 80% reduction in PASI score was 7·3 ± 2·4 weeks compared to 4·2 ± 2·1 weeks with CyA and CP ( P < 0·05). Four weeks after withdrawal of treatment the average percentage deterioration in PASI score was 29·2 in the CyA group and 17·8 in the CyA + CP group. This difference was not significant.
Thus, the addition of CP to CyA in the management of psoriasis cleared psoriasis faster than CyA alone but did not slow the relapse rate. It would seem that the initiating factor responsible for attracting TH cells into the epidermis is not cleared by either treatment.     

Combined treatment with low-dose cyclosporine and calcipotriol/betamethasone dipropionate ointment for moderate-to-severe plaque psoriasis: a randomized controlled open-label study

Combination therapy is a common approach to psoriasis, aimed at improving clinical response and minimizing the risk of side effects. The aim of this pilot randomized open-label study was to evaluate the efficacy and safety of the combination of low-dose cyclosporine (CsA) with calcipotriol-betamethasone dipropionate (CBD) ointment in the treatment of psoriasis. Sixty patients with moderate-to-severe plaque psoriasis were randomized to receive CsA, 2 mg/kg/day, combined with CBD ointment (n = 30) or CsA, at the same daily dosage, in combination with an emollient (n = 30), for 8 weeks. The primary efficacy parameter was the Psoriasis Area and Severity Index (PASI) 75 response rate at 8 weeks. Combination therapy with CsA and CBD ointment was more effective than CsA and emollient treatment, with statistically significant results, particularly less itching after 4 and 8 weeks and PASI reduction at all post-baseline visits. Significantly more patients treated with CsA + CBD achieved the PASI 75 at 8th week (87% vs 37% in the CsA-emollient group; p = 0.0001). The efficacy results were paralleled by the investigator and patient's global assessment of disease severity at the end of study. Our results suggest that the addition of CBD ointment to low-dose CsA enhances clinical response and improves the risk/benefit ratio.     

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.     

Efficacious treatment of psoriasis with low‐dose and intermittent cyclosporin microemulsion therapy

Cyclosporin is used for moderate to severe psoriasis and improves not only the skin lesions but also quality of life of the patients. To improve its safe use, we evaluated a low‐dose, intermittent regimen of cyclosporin in the treatment of psoriasis vulgaris. Seventy‐three patients received approximately 2.5 mg/kg per day of cyclosporin microemulsion twice daily before breakfast and dinner for 2–12 weeks until 75% reduction was achieved in Psoriasis Area and Severity Index (PASI) score. When the skin lesions relapsed after cessation of cyclosporin and showed less than 50% reduction from baseline in PASI score, cyclosporin was restarted. This cessation and restart cycle was repeated if necessary. Treatment outcomes were assessed at 12, 48 and 96 weeks after initiation of the therapy. The initial dose of cyclosporin was 2.32 ± 0.27 (standard deviation [SD]) mg/kg per day. At baseline, the mean PASI score was 11.3 ± 5.3 (SD). An average of 49.8 ± 23.8 (SD) days of the therapy achieved PASI 75% reduction. In 20 of 73 patients, the second course of cyclosporin was required. The mean interval between the first and second course was 94 days. An average of 60.8 ± 26.9 days was required to achieve PASI 75% reduction in the second course, which was not significantly longer than that in the first course. Only six patients required cyclosporin for 96 weeks. The adverse effects included one case of hypertension. Our study suggests that low‐dose, intermittent cyclosporin microemulsion is efficacious for the treatment of moderate to severe psoriasis.     

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

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

Combined treatment with etanercept 50 mg once weekly and narrow-band ultraviolet B phototherapy in chronic plaque psoriasis

The combination of etanercept, a tumour necrosis factor α inhibitor, with narrow-band ultraviolet B (NB-UVB) phototherapy has recently been reported to be effective in moderate-to-severe plaque psoriasis, yielding better results than either monotherapy. To assess the efficacy and safety of this combined treatment using the lower approved etanercept dosage. In this single-arm open-label study patients received etanercept 50 mg once weekly combined with NB-UVB phototherapy three times weekly for 8 weeks, followed by etanercept alone until week 12. We evaluated the proportion of patients achieving 75%, 90% and 100% improvement of their initial PASI score (PASI75, PASI90, and PASI100, respectively). Patients were 19 men and 14 women, mean age 48.3 years ± 12.1 standard deviation (SD) and mean baseline Psoriasis Area and Severity Index (PASI) score 22.5 ± 7.5. On treatment weeks 4, 8, and 12, 24.2%, 66.7%, and 81.8% of patients achieved PASI75; 8.0%, 15.1%, and 57.6% reached PASI90, and 0%, 6.0%, and 24.2% attained PASI100, respectively. There were no severe side effects. Low-dosage etanercept combined with NB-UVB phototherapy is an effective, safe and economical approach to treat moderate-to-severe plaque psoriasis. Further studies are clearly required to assess its long-term efficacy and safety.     

Widespread plaque psoriasis responsive to mycophenolate mofetil

A woman with a long history of widespread plaque psoriasis unresponsive to and/or intolerant of phototherapy, retinoids, methotrexate and cyclosporin was successfully treated with mycophenolate mofetil. Remission was maintained on doses between 1 and 1.5 g/day for 18 months without adverse effects.     

Open-label, single-center, safety dose escalation trial of alefacept for the treatment of moderate to severe chronic plaque psoriasis

BACKGROUND: Alefacept (Amevive) is a fully human LFA-3/IgG1 fusion protein with a dual mechanism of action inhibiting T-cell activation and selectively reducing memory T cells. Alefacept is currently approved as a 12-week course of weekly 15 mg intramuscular (IM) injections for the treatment of adults with moderate to severe chronic plaque psoriasis. In clinical trials using the currently approved dosing regimen, 33% and 57% of patients achieved a 75% or greater or 50% or greater reduction in Psoriasis Area and Severity Index score (PASI 75 and PASI 50), respectively, after one course of alefacept. OBJECTIVE: To evaluate the tolerability and efficacy of alefacept 15 mg IM weekly for 6 weeks followed by alefacept 30 mg IM weekly for 6 weeks. DESIGN: Open-label, single-center, dose escalation study of alefacept. PATIENTS: Adult patients with chronic plaque psoriasis involving a minimum body surface area of 10% and with a minimum PASI of 12. INTERVENTION: Patients were treated with alefacept 15 mg IM for 6 weeks followed by alefacept 30 mg IM for an additional 6 weeks; doses were held for CD4 counts < 200 cells/mm(3) or evidence of a clinically significant infection. MAIN OUTCOME MEASURE: Efficacy was evaluated by PASI and Physician Global Assessment (PGA) at baseline, week 7, and 2, 6, 12, and 24 weeks post-treatment. RESULTS: Sixteen patients were enrolled; at 6 weeks post-treatment, the PASI mean reduction was 39%, with continued improvement to 46% at 12 weeks post-treatment. The PASI 90, PASI 75, and PASI 50 responses at 12 weeks post-treatment were 6% (1 of 16), 13% (2 of 16), and 38% (6 of 16), respectively; 12% (2 of 16) of patients achieved a PGA of clear to almost clear at 12 weeks post-treatment. The overall PASI 75 and PASI 50 responses were 19% (3 of 16) and 38% (6 of 16), respectively. CONCLUSION: The treatment regimen of alefacept 15 mg IM for 6 weeks followed by alefacept 30 mg IM for 6 weeks was well tolerated by our patients. There was no increased incidence of infections when patients were treated with alefacept 30 mg compared with the 15 mg dose. The increased dose of alefacept 30 mg for the last 6 weeks of a 12-week course did not appear to yield a higher efficacy rate compared with historical controls.     

Clinical effectiveness and safety experience with alefacept in the treatment of patients with moderate-to-severe chronic plaque psoriasis in Taiwan: results of an open-label, single-arm, multicentre pilot study

Background  The effectiveness and safety of alefacept for the treatment of moderate-to-severe chronic plaque psoriasis has been established in several clinical trials conducted in the United States and Europe. No clinical trial of alefacept has been conducted in Asia.
Objective  To determine the effectiveness and safety of alefacept in the treatment of psoriasis in Chinese population.
Design and methods  This was an open-label, single-arm, multicentre pilot study conducted at three centres. Patients with a body surface area ≥ 10% and psoriasis area and severity Index (PASI) ≥ 12 were given 15 mg alefacept intramuscularly once a week for 12 weeks and were then followed up for a further 12 weeks.
Results  A total of 46 patients was enrolled. Only one subject (2%) achieved a ≥ 75% improvement in PASI at week 14. The median improvement in PASI at week 14 after the 12-week treatment was 39%. At any time during the 6-month course, 3 subjects (7%) achieved a Physician Global Assessment (PGA) of 'almost clear', and a ≥ 50% and ≥ 75% improvement in PASI was seen in 46% and 9%, respectively. There is a trend for decreased counts of CD4⁺ and CD8⁺ cells after alefacept treatment, but subjects who achieved PASI50 showed a lesser degree of decrease in CD4⁺ and CD8⁺ counts compared with those in patients who did not achieve PASI50.
Conclusions  This small pilot study indicated that intramuscular alefacept was effective and safe in psoriasis in Chinese patients over 12 weeks of treatment. Further studies are needed to clarify the reason for low PASI 75 effectiveness and the paradoxical lesser decline of CD4⁺ and CD8⁺ T cells in those who responded.     

Efalizumab: results of a 3-year continuous dosing study for the long-term control of psoriasis

BACKGROUND: Efalizumab, a T-cell-targeted, recombinant, humanized, monoclonal IgG1 antibody, inhibits key T-cell-mediated steps in the pathogenesis of psoriasis. Efalizumab is approved for the treatment of moderate-to-severe chronic plaque psoriasis in adults in more than 50 countries. OBJECTIVES: To evaluate the efficacy and safety of long-term, continuous efalizumab therapy in patients with psoriasis. METHODS: This open-label, multicentre phase III study enrolled 339 patients with moderate-to-severe chronic plaque psoriasis. During the initial 3-month phase, patients received subcutaneous efalizumab 2 mg kg(-1) weekly with randomization to receive concomitant fluocinolone acetonide or placebo ointment during month 3. The second phase was a long-term observational period; patients achieving a >or=50% improvement in the Psoriasis Area and Severity Index (PASI) score were eligible to receive efalizumab 1 mg kg(-1) weekly for up to 33 months. The final 3-month treatment period was an optional transition period for patients who completed the 33-month segment before efalizumab became commercially available. RESULTS: After 3 months, 41.3% of patients achieved a >or=75% improvement in PASI (PASI-75) and 13.0% achieved a >or=90% improvement (PASI-90). Continued improvement was observed: 45.4% and 24.5% achieved PASI-75 and PASI-90, respectively, at the end of the observational phase. The safety profile was stable, with no new or no increase in common events over 36 months of treatment. CONCLUSIONS: This was the longest continuous study using a biologic therapy for psoriasis. Clinical benefit of efalizumab improved over the first 18 months and was maintained during 36 months of continuous therapy. Long-term efalizumab therapy is appropriate for many patients with plaque psoriasis.     

Placebo Response in Two Long-Term Randomized Psoriasis Studies that were Negative for Rosiglitazone

Background:Previous research has suggested that the thiazolidinedione rosiglitazone may possess antipsoriatic activity. Objective:To compare the efficacy and safety of rosiglitazone with that of placebo in the treatment of chronic plaque psoriasis. Methods:Two large-scale, randomized, double-blind, multicenter studies (study A, n = 1563; study B, n = 1032) were conducted over 52 weeks (plus optional 44 weeks safety extension) in an outpatient setting. The subjects (aged 18–75 years) had moderate-to-severe chronic plaque psoriasis affecting ≥10% body surface area (BSA) with plaques of any elevation above normal-appearing skin (or ≥6% BSA involvement with marked elevation) and had not used phototherapy during the previous month or thiazolidinediones within the previous 3 months. Rosiglitazone was administered as 2, 4, or 8mg tablets once daily. The main outcome measure was the proportion of subjects achieving ≥75% improvement from baseline in the Psoriasis Area and Severity Index (PASI 75) at week 26. both studies for subjects receiving placebo, the PASI 75 was 9% (48/506) and the PASI 50 (proportion of subjects who achieved at least 50% improvement from baseline) was 27% (135/506). In addition, few subjects withdrew from placebo or rosiglitazone treatment because of ‘lack of efficacy’ and the majority persisted in the year-long study. Conclusion: While these large-scale, robust studies demonstrated that rosiglitazone is not active in psoriasis, they also showed that for a large proportion of subjects receiving placebo, the expectation of a successful treatment, the favorable adverse effect profile of the drug, and the supportive environment of a clinical study conferred beneficial effects. These results may have implications for the design of future placebo-controlled studies in patients with psoriasis.     

Real world data from the use of secukinumab in the treatment of moderate‐to‐severe psoriasis,including scalp and palmoplantar psoriasis: A 104‐week clinical study

Several clinical studies demonstrated the safety and efficacy of the interleukin‐17 inhibitor secukinumab in the systemic treatment of moderate‐to‐severe psoriasis, as well as psoriatic arthritis (PsA) in adults, whereas real‐world data is limited. A single‐center clinical study was performed to evaluate in real‐world practice the efficacy of secukinumab up to Week 104 of treatment in moderate‐to‐severe chronic plaque psoriasis, including scalp and palmoplantar involvement, according to Physician Global Assessment (PGA), PASI75/90/100 and scalp, and palmoplantar PGA. Drug survival, the safety profile of secukinumab, and patient's quality of life were also assessed during a 2‐year observation period. Out of 83 patients included, 56.3% were biologic‐naïve, and 94% had scalp, 25.3% palmoplantar, and 43.9% joint involvement. At Week 16, PASI75/PASI90/PASI100 were observed in 83.8/70.0/46.3%, respectively. Scalp and palmoplantar PGA were rapidly improved, with 98.7 and 95.5%, respectively, reaching clear/almost clear skin at Week 16. After 104 weeks, drug survival was 74.5%. A significant improvement of the quality of life was observed. Biologic‐naïve patients without coexisting PsA benefited the most. Real‐world data demonstrated secukinumab efficacious in chronic plaque psoriasis, including specific locations such as scalp and palmoplantar psoriasis with a safety profile similar to that in clinical trials.     

Systematic review on rapidity of onset of action for interleukin-17 and interleukin-23 inhibitors for psoriasis

Several novel biologics are available or in development for moderate-to-severe plaque psoriasis. These drugs may differ in time until Psoriasis Area and Severity Index (PASI) response is obtained. In this systematic review, we examined the time to onset of action for interleukin (IL)-17 and IL-23 agents in the treatment of psoriasis. The primary objective was the weighted mean time needed for 25% and 50% of patients with psoriasis to achieve PASI90. The medical databases PubMed, Web of Science and EMBASE were searched using the following terms: psoriasis AND (ixekizumab OR secukinumab OR brodalumab OR risankizumab OR guselkumab OR tildrakizumab). A total of 27 studies were included for data extraction and qualitative synthesis, and 26 of these were quantitatively analysed. The shortest time to 25% and 50% of patients to achieved PASI90 were seen with brodalumab 210 mg every 2 weeks (Q2W; 3.5 weeks and 6.2 weeks, respectively) followed by ixekizumab 80 mg Q2W (4.1 and 7.4 weeks, respectively) and ixekizumab 80 mg Q4W (4.6 and 8.1 weeks, respectively) dosages. In conclusion, clinical trials yielded shorter time to onset of action in studies assessing approved dosing ranges of IL-17 inhibitors compared with studies assessing IL-23 inhibitors.     

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.     

Long-term maintenance treatment of moderate-to-severe plaque psoriasis with infliximab in combination with methotrexate or azathioprine in a retrospective cohort

Background  Effective, fast-acting and safe therapies are needed for long-term maintenance treatment of psoriasis. In October 2005, infliximab was approved for the treatment of moderate-to-severe plaque psoriasis, but long-term data are limited.
Objective  To evaluate the effectiveness of infliximab, used in combination with methotrexate or azathioprine, in maintaining clinical benefit in patients with moderate-to-severe psoriasis.
Methods  The medical charts of 23 patients treated with infliximab from August 2001 to February 2007 were retrospectively reviewed. Most patients received either infliximab 3 mg/kg (17 of 23) or 5 mg/kg (1 of 23) in combination with methotrexate, while 5 of 23 patients received infliximab 5 mg/kg in combination with azathioprine. Psoriasis Area Severity Index (PASI) score and adverse events were recorded at every infliximab infusion visit at the hospital.
Results  Patient data were available for a minimum of 4 weeks and up to 5 years and 5 months. At week 14, 91.3% achieved PASI 50, 69.6% achieved PASI 75, and 39.1% achieved PASI 90. Only two patients discontinued therapy due to loss of response: one after 15 months and one after 3 years. All other patients displayed a good clinical response (≥ PASI 50) and were still receiving this regimen at last observation. Combination regimens of infliximab with methotrexate or azathioprine were well tolerated, and only one patient discontinued therapy because of an adverse event (lung embolism) after two infusions with infliximab.
Conclusions  Long-term (> 1 year) maintenance therapy of infliximab combined with methotrexate or azathioprine is effective and well tolerated for moderate-to-severe plaque-type psoriasis.

Conflicts of interest

None declared