Clearance Of Psoriasis Research Articles

PSS29 - The Relationship of Quality of Life and Complete Psoriasis Clearance Over Time – Analyses From Brodalumab Trial Datasets

PSS29 - The Relationship of Quality of Life and Complete Psoriasis Clearance Over Time – Analyses From Brodalumab Trial Datasets

The effect of secukinumab on moderate-to-severe scalp psoriasis: Results of a 24-week, randomized, double-blind, placebo-controlled phase 3b study

Moderate-to-severe scalp psoriasis has not been evaluated in prospective trials of patients without moderate-to-severe body psoriasis. Evaluate the efficacy and safety of secukinumab in moderate-to-severe scalp psoriasis. In this 24-week, double-blind, phase 3b study, 102 patients were randomized 1:1 to subcutaneous secukinumab 300mg or placebo at baseline, weeks 1, 2, and 3, and then every 4weeks from week 4 to 20. The primary efficacy variable was 90% improvement of Psoriasis Scalp Severity Index (PSSI 90) score from baseline to week 12. At week 12, PSSI 90 (secukinumab 300mg vs placebo, 52.9% vs 2.0%) and Investigator's Global Assessment modified 2011 scalp responses of 0 or 1 (secukinumab 300mg vs placebo, 56.9% vs 5.9%) were significantly greater with secukinumab 300mg than placebo (P<.001 for both). In addition, significantly more patients achieved complete clearance of scalp psoriasis at week 12 with secukinumab 300mg than placebo (35.3% vs 0%; P<.001). The median time to 50% reduction in PSSI score was 3.29weeks with secukinumab 300mg. The safety profile of secukinumab was consistent with previous phase 3 studies. There was no active comparator arm. Secukinumab is efficacious and well-tolerated for patients with extensive moderate-to-severe scalp psoriasis.

A randomised half body prospective study of low and medium dose regimens using the 308 nm excimer laser in the treatment of localised psoriasis

This study compared two dose-escalation regimens using the 308 nm excimer laser treating localised plaque psoriasis, to determine the optimal regimen. A randomised, left–right body trial was designed including patients aged >18 years with localised plaque psoriasis (<10% body surface area). The standard/low dose regimen started at 70% of the minimal erythema dose (MED), with 20% dose increments. The medium dose regimen commenced at 200% MED, with 25% increments. Patients were treated until disease clearance or a maximum of 36 treatments. Fifteen patients aged 28–55 years completed the study. Psoriasis severity index scores analysed at weeks 0, 6 and 12 showed a significant reduction with each regimen (p < 0.0001). Six patients cleared, seven had significant improvement with uneven clearance of plaques and two failed. Average remission was four months (range 1–12 months). There was a significant reduction in DLQI (p = 0.014). Excimer laser improved psoriasis and reduced DLQI scores, but clearance was incomplete for many patients and remission was short-lived. Adverse effects of pain and blistering were commoner with the medium dose regimen, without any benefit in psoriasis clearance.

Ixekizumab, an interleukin-17A specific monoclonal antibody, for the treatment of biologic-naive patients with active psoriatic arthritis: results from the 24-week randomised, double-blind, placebo-controlled and active (adalimumab)-controlled period of the phase III trial SPIRIT-P1

ObjectiveTo assess the safety and efficacy of ixekizumab, a monoclonal antibody that inhibits interleukin-17A, in a double-blind phase III trial enrolling patients with active psoriatic arthritis (PsA).MethodsPatients naive to biologic...

Predictors of long-term drug survival for infliximab in psoriasis.

Limited information is available regarding factors associated with long-term drug survival of infliximab for psoriasis in real life. The main aim pf this study was to identify predictors of long-term (>12 months) drug survival among patients treated with infliximab for psoriasis in a real-world clinical setting. Retrospectively collected data, relating to disease, patient characteristics and treatment procedures, in a multicentre observational cohort of patients with moderate-to-severe plaque psoriasis treated with infliximab at eight university hospitals, 120 of whom maintained a response to infliximab for more than 12 months, were compared with prospectively collected data in the same centres from 54 patients who experienced secondary loss of response within a 12-month period. Mean duration of drug survival of infliximab in patients with long-term drug survival was 41.12 months ± 20.64 SD vs. 8.5 months ± 2.43 SD in patients with a secondary loss of response. Multivariate analysis identified greater disease severity at treatment onset (PASI score >12) (OR = 5.18, 95% CI: 1.60-16.77, P = 0.006), high levels of initial psoriasis clearance (PASI-90 reduction or equivalent) (OR = 18.50, 95% CI: 4.56-74.45, P = 0.0001) and combination with methotrexate (OR = 13.15, 95% CI: 1.46-118.79, P = 0.022) as independent predictors of long-term drug survival and sustained efficacy of infliximab. Positive predictors for long-term drug survival of infliximab in real life were identified. Their impact on treatment management should be addressed in further prospective trials.

Dipeptidyl peptidase-4 inhibition and narrow-band ultraviolet-B light in psoriasis (DINUP): study protocol for a randomised controlled trial.

BackgroundModerate to severe psoriasis is a systemic inflammatory disease associated with insulin resistance, obesity and type 2 diabetes (T2DM). Sitagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor that improves glycaemia and has a marketing authorisation for the treatment of T2DM. Non-immunosuppressive therapies that are effective for psoriasis and its associated comorbidities would be a significant advance in the treatment of this chronic disease.Methods/DesignThis is a single centre, 39-week, prospective, randomised, open label, clinical trial of oral sitagliptin (Januvia®) in psoriasis patients who are due to undergo a course of narrow-band ultraviolet-B (NB-UVB) phototherapy. We plan to enrol 120 participants and allocate participants on a random and 1:1 basis to receive sitagliptin 100 mg daily for 24 weeks combined with NB-UVB or NB-UVB monotherapy. Participants will be followed up for 12 weeks after sitagliptin therapy is discontinued. The primary endpoint is the change in Psoriasis Area and Severity Index (PASI) 24 weeks after treatment initiation. Secondary endpoints include cumulative NB-UVB dose, number of NB-UVB treatments required to clear psoriasis, proportions of participants who achieve PASI-50 (50 % reduction in PASI from baseline), PASI-75, PASI-90 and the proportion of participants who relapse in each group. We will also analyse changes in cardiovascular disease risk factors, serum cytokine and hormone levels and peripheral blood mononuclear expression of immune proteins at 24 and 36 weeks. A subgroup of participants will have skin biopsies taken and analysed for skin levels and expression of immune cells, receptors, hormones and immune proteins. The genetic or epigenetic profile that predicts best response to DPP-4 inhibitor therapy will be analysed. The safety endpoints include the rate and severity of adverse events.DiscussionThis is the first randomised clinical trial assessing dipeptidyl peptidase-4 inhibition therapy in psoriasis. We hypothesise that sitagliptin therapy in combination with NB-UVB improves psoriasis severity compared to NB-UVB monotherapy.Trial registrationClinicalTrials.gov Identifier NCT02347501 (Date of registration: 27 January 2015).

Interleukin-17 inhibition: a route to psoriasis clearance?

Interleukin-17 inhibition: a route to psoriasis clearance?

Azathioprine pulse therapy in the treatment of psoriasis nail: A case series

Abstract Background Various treatments available for treating nail changes in psoriasis are able to clear the lesions but relapse is common. While treating psoriasis with azathioprine pulse therapy, it was observed that the lesion of nails including pitting, dystrophy, etc. was also cleared. Aim To check whether intermitted high dose (IHD) with continuous low dose azathioprine given to clear psoriasis could also clear the nail changes and produce prolonged remission. Methods 7 out of 60 psoriasis patients treated with azathioprine pulse therapy (APT) had psoriatic lesion on nails also. All the 60 patients received azathioprine pulse therapy for treating psoriasis, which contain azathioprine 500 mg given on 3 consecutive days and was repeated every month on the same date along with azathioprine100 mg orally in between the IHD. The entire treatment schedule was divided into four phases. Phase I continued till complete clearance of all lesions on the skin. In Phase II, 9 more APTs are given. In Phase III, only azathioprine 100 mg is continued for 9 months. In Phase IV, 100 mg was also stopped and patients were followed up without any treatment. Results Out of 7 patients, 5 had pitting of nails which cleared in 2–13 months. All the nails having pitting are in remission from 14 to 106 months. One patient had dystrophy of all nails of 2-yr duration, which cleared in 3 months. However, he developed relapse along with relapse of psoriasis after 26 months in remission, which subsequently cleared in 10 months on continuing APT and he is in remission since 62 months. White nails in 1 patient cleared in 17 months, and she/he is in remission since 17 months. Conclusion Azathioprine pulse therapy regimen is able to put psoriatic nail changes into prolonged remission.

24 hour forecast of the surface UV for the antipsoriatic heliotherapy in Poland

Analyses of the spectral and broad-band UV data collected at Belsk (20.79°E, 51.84°N), Poland, show that standard broad-band instrument, Solar Light (SL) 501A, could be used for measurements of both erythemal and antipsoriatic irradiance. A prognostic model is proposed for the next-day duration of outdoor exposure required to receive a dose, the so-called minimum antipsoriatic dose (MAD), equivalent to that received by standard antipsoriatic daily treatment in the phototherapy cabinet containing TL-01 fluorescent tubes. The model uses the 24h forecast of the column amount of ozone (to predict next day clear sky UV irradiance), and low- and mid-level cloudiness (to estimate a reduction of the clear-sky UV irradiation due to clouds). The predicted duration of sunbathing required to receive a dose of 1 MAD matches the observed value, i.e. the correlation coefficients is 0.68. If the model predicts the antipsoriatic exposure over 1 MAD threshold the observed dose will be also above this threshold in 91% of cases. Thus, the model could be used for planning the next-day outdoor exposure to clear psoriasis. Hourly resolved maps, starting from 6am up to 1pm (GMT), showing the duration of antipsoriatic exposure over Poland are made public. The model provides a tool for a psoriatic patient to find the sunbathing starting time and its duration, which has the same healing potential as a single indoor phototherapy session.

Azathioprine Pulse Therapy in the treatment of psoriatic arthritis: A case series

Background/objectiveTreatment available for treating psoriasis of joint are able to clear the lesions but relapse is common. While treating psoriasis with Azathioprine Pulse Therapy, it was observed that the involvement of joints (arthritis of small and big joints) also cleared. To see whether intermittent high dose (IHD) and continuous low dose (CLD) azathioprine given to clear psoriasis also clear the joint involvements and produce prolong/permanent remission. MethodsSix out of 60 psoriasis patients treated with azathioprine pulse therapy (APT) had joints involvement. All received azathioprine pulse therapy for treating psoriasis which contain azathioprine 500 mg given on three consecutive days and was repeated every month on the same date along with azathioprine100 mg orally in between the IHD. The entire treatment was divided into four phases. Phase I, continued till clearance of all lesions of psoriasis. In phase II nine more APT is given. In phase III only azathioprine100 mg was continued for 9 months. In phase IV azathioprine100 mg was also stop and patients were followed up without any treatment for any recurrence till the end of the study. ResultSix patients with joint pain and arthritis cleared in 1–12 months and are in remission since 35–95 months. ConclusionsThus azathioprine pulse therapy regimen is able to put psoriatic arthritis into prolong/permanent remission.

Broadband ultraviolet A in the treatment of psoriasis vulgaris: a randomized controlled trial

Broadband ultraviolet A (BB-UVA) has been successfully used in the treatment of scleroderma, a UVA1-responsive dermatosis. To compare the efficacy of BB-UVA versus psoralen+UVA (PUVA) in psoriasis treatment and assess apoptosis as an effector mechanism. This randomized controlled trial included 61 patients with chronic plaque psoriasis randomly divided into group I or II. Group I were further randomized to either IA or IB who received UVA 10 or 15J/cm(2) per session, respectively, while group II received PUVA. Therapy was delivered thrice weekly until clearance or 48 treatments at most. The primary outcome measured was clearance of psoriasis. Dermal lymphocytic counts and bcl-2 expression were measured in 20 patients from each group. Final Psoriasis Area Severity Index scores were reduced within each group. The UVA group achieved results comparable to PUVA until session 24 but failed to match it at final evaluation, with significantly better clinical, immunohistochemical, and histopathological results achieved by PUVA (P≤0.05). Both modalities caused a reduction in dermal lymphocytic counts and epidermal bcl-2 expression. BB-UVA appears to be safe and acceptable for the treatment of chronic plaque psoriasis possibly through bcl-2-mediated apoptosis of keratinocytes and epidermal lymphocytes.

Investigation of cutaneous photoadaptation to narrowband ultraviolet B

Photoadaptation describes the skin's ability to withstand an increased dose of ultraviolet (UV) radiation with repeated exposure, and this is the reason for exposure doses being increased during a course of phototherapy. However, directly measured data on photoadaptation are available only for broadband (BB) and not narrowband (NB)-UVB. To measure photoadaptation to narrowband UVB. We measured the degree of photoadaptation in patients with psoriasis during a standard course of NB-UVB phototherapy. The minimal erythemal dose (MED) was measured before and towards the end of a course of phototherapy. An adaptation factor (AF) was calculated for each patient using the ratio of final MED to initial MED. Sigmoid dose-response curves were also constructed. MED results were available for 50 patients (mean age 44years, 28 female). The mean AF was 2·7 (95% confidence interval 2·4-3·0). There was no significant correlation between AF and skin type or initial MED. Dose-response curves were right shifted and parallel after phototherapy, and there was no significant difference in the maximum slope (P=0·73). The photoadaptation caused by NB-UVB is considerably less than that reported for BB-UVB. The variation in photoadaptation between patients was not explained by skin type or baseline MED. Physical factors (such as tanning and epidermal thickening) are probably sufficient to account for photoadaptation, rather than downregulation of the inflammatory response. These data should help in the design of phototherapy protocols for NB-UVB to achieve optimal clearance of psoriasis.

Are topical keratolytic agents needed in the treatment of scalp psoriasis?

Topical corticosteroids are the primary treatment for scalp psoriasis. Keratolytic agents are promoted as adjunctive treatments. However, complex treatment regimens may result in poor adherence and outcomes. To evaluate the evidence for the need for use of topical keratolytic agents as opposed to topical corticosteroid monotherapy in the treatment of scalp psoriasis. A review of the literature was performed seeking clinical trials using topical keratolytics, topical corticosteroids or the combination for treatment of scalp psoriasis. Complete clearance of scalp psoriasis can be achieved in 10-78% of patients using topical corticosteroids alone, in 3% of patients using topical keratolytics alone, and in up to 84% using a combination of topical keratolytics and topical steroids. Clinical trials comparing the combination of keratolytics and topical corticosteroids versus topical corticosteroids alone found marginally more efficacy using combination regimens. We could not find any long term study evaluating the efficacy of combination therapy in scalp psoriasis and its effect on the patients' adherence. High potency topical corticosteroids are usually effective in treating scalp psoriasis in clinical trials. Poor efficacy in clinical practice may be owing to poor adherence to the treatment regimen. Using a keratolytic agent in conjunction with a topical corticosteroid may provide marginal additional benefit in clinical trials, but that benefit is likely outweighed by the downside of complicating treatment and reducing adherence in the clinical setting, unless a single product containing both medications were used.

Merits of Maintenance Phototherapy for Psoriasis

Psoriasis is a chronic skin condition that requires long-term maintenance therapy, sometimes lifelong. Phototherapy (narrowband ultraviolet B, broadband ultraviolet B, and psoralen plus ultraviolet A) is a safe and effective method of treating generalized psoriasis. Although there are numerous publications demonstrating the efficacy of phototherapy for the initial clearance of psoriasis, there has not been a review evaluating the merits of phototherapy for the maintenance of remission in patients with psoriasis once they clear their skin disease. We searched PubMed for articles evaluating the efficacy of phototherapy for maintaining remission in patients with treated generalized psoriasis. The majority of published trials supported the use of maintenance phototherapy after clearance of generalized psoriasis. Typically, the studies showed that maintenance phototherapy reduces the rate of disease relapse and prolongs the duration of remission of psoriasis after initial clearance. There is available evidence supporting phototherapy, including psoralen plus ultraviolet A, as a safe and effective treatment option for maintenance of remission in patients with generalized psoriasis. Further studies are needed to adequately assess narrowband ultraviolet B for maintenance therapy, and additional studies are also necessary to directly compare the efficacy of different phototherapy types for remission maintenance.

Treatment of severe psoriasis

Despite the great advances brought about by biologic therapies, treatment of moderate-to-severe psoriasis often represents a challenge. Associated comorbidities may hamper the use of ciclosporin or methotrexate at effective doses, and obesity or heavy weight reduce the therapeutic expectations of systemic treatments, especially with regard to optimal response, which should be the ultimate goal of therapy. Combination therapy has been recognized to be an effective way of improving therapeutic response, and methotrexate at low doses seems especially well suited for combination with biologics, by improving response rates and reducing drug clearance and development of anti-drug antibodies. Secondary lack of response to biologics does occur in a small percentage of patients, and accounts in part for reduced drug survival in dermatology patients. In some cases, especially when the presence of anti-drug antibodies can be demonstrated, switching to another biologic agent in the same class may be effective, but some patients appear to be prone to developing anti-drug antibodies against several agents. In some cases, switching to another class of biologics (e.g. anti-p40 antibodies) can prove to be a very effective alternative, with an excellent safety profile. The present case report illustrates the optimization of therapeutic response to biologics using combination therapy and achieving long-lasting clearance of psoriasis following switching to ustekinumab in a patient who had shown secondary loss of response to several biologics.

Effectiveness of heliotherapy for psoriasis clearance in low and mid-latitudinal regions: A theoretical approach

The action spectrum for psoriasis clearance is reconstructed taking into account the results obtained in the early 1980s. The antipsoriatic action spectrum is used for weighting the medical cabinet UV spectra, and the solar spectra measured in San Diego (USA) and Belsk (Poland). The mean cumulative antipsoriatic effective dose of 450mJcm−2, due to TL-01 (UVB narrowband) tubes, is taken by a patient with skin phototype II during routine 20 phototherapy sessions carried out in a phototherapy cabinet in the Medical University of Łódz. Thus, the daily mean dose of value 22.5mJcm−2 is proposed as the threshold for daily solar dose for numbers of out-door exposures to clear psoriasis. We assume that the heliotherapy will last a whole month with every day 2h exposition to the direct sunlight around local noon. The heliotherapy will be successful if weather conditions permit at least 20days with the daily exposure over the threshold. The minimum cumulative ambient erythemal dose, necessary for psoriasis clearance, is estimated as 144 standard erythema dose (SED) for the whole heliotherapy period. We find that heliotherapy could be effectively used in March through October (San Diego) and in June through August (Belsk). Thus, the heliotherapy against psoriasis is possible not only at southern resorts but even at the mid-latitude sites.

Efficacy of Psoralen UV‐A therapy vs. Narrowband UV‐B therapy in chronic plaque psoriasis: a systematic literature review

Oral 8-methoxypsoralen-UV-A (PUVA) and Narrowband UV-B (NB-UVB or UVB TL-01) are well established treatments for chronic plaque psoriasis but there is limited evidence regarding their respective efficacy. To prepare for evidence-based recommendations concerning the practical use of oral 8-methoxypsoralen-UV-A and Narrowband UV-B in psoriasis, a systematic review to assess respective response rates, remission duration and predictive factors of efficacy was performed. A systematic search was carried out in PubMed, Cochrane and Embase databases, using the key words 'Psoriasis', 'UVB therapy', 'UVA therapy' for the period from 1980 to December 2010. The initial literature search identified 773 articles. The final selection included 29 randomized controlled trials: 18 were about the efficacy of PUVA, eight about the efficacy of NB-UVB and three directly compared PUVA vs. NB-UVB. The response rate defined by 75% or more improvement in PASI was 80% with PUVA vs. 70% with NB-UVB. The meta-analysis of the three comparative studies found a higher probability of remission at 6 months with PUVA than with NB-UVB [OR = 2.73 (95% CI 1.19-6.27), P = 0.02]. The choice of initial dose, according to skin type, the minimal erythemal dose or minimal phototoxic dose, incremental regimen and periodicity of the sessions did not appear to be predictive factors of efficacy for PUVA or NB-UVB. Despite methodological limitations in trials, the number of sessions needed for psoriasis clearance appeared to be lower with PUVA than with NB-UVB (approx. 17 vs. 25, respectively). PUVA and NB-UVB are both effective therapies in treatment of psoriasis. Our results suggest that compared with NB-UVB, PUVA tends to clear psoriasis more reliably, with fewer sessions, and provides with longer lasting clearance. However, the long-term safety of PUVA, especially its cutaneous carcinogenic risk, and the easier administration procedure often lead dermatologists to prefer NB-UVB as first line phototherapy treatment in plaque type psoriasis.

Effective treatment of etanercept and phototherapy-resistant psoriasis using the excimer laser

Treatment of moderate-to-severe plaque psoriasis often requires the use of phototherapy or systemic therapy, which includes immunosuppressants, retinoids, and biologic agents. Although biologic use is becoming increasingly popular, it is not uncommon for patients to experience treatment failure. We describe a patient who had a suboptimal response to etanercept monotherapy after twelve weeks of induction dosing (50 mg twice weekly), as well as to a combination of etanercept (50 mg once weekly-maintenance dosing) and narrowband ultraviolet B (NB-UVB) phototherapy three times weekly for an additional twelve weeks. Noticeable improvement was noted after the addition of NB-UVB and the patient's promising response to phototherapy influenced further management. Etanercept and NB-UVB were discontinued and the patient was initiated on excimer laser treatments twice weekly. After 4 weeks, the patient had a 75 percent reduction in Psoriasis Area Severity Index (PASI) score and after 7 weeks had over 95 percent clearance of psoriasis. The unique properties of the excimer laser may account for its clinical efficacy in our patient as well as in other cases of recalcitrant psoriasis. We propose that the excimer laser be considered in cases of biologic or conventional phototherapy failure in addition to being a standard treatment option or adjunct for the treatment of psoriasis.

Glutathione S-transferase genotype is associated with sensitivity to psoralen-ultraviolet A photochemotherapy

There is marked interpatient variation in responses to psoralen-ultraviolet A (PUVA) photochemotherapy. Identification of molecular biomarkers of PUVA sensitivity may facilitate treatment predictability.The glutathione S-transferases (GSTs) influence cutaneous defence against UV radiation-induced oxidative stress and are therefore candidate biomarkers of PUVA sensitivity. Several human GSTs, including GSTM1 and GSTT1, are polymorphic, and null polymorphisms have been associated with increased UVB erythemal sensitivity and skin cancer risk. PUVA also increases skin cancer risk. To investigate the effect of GST genotype on PUVA sensitivity. We investigated GST genotype in patients starting PUVA (n=111) and the effects of 8-methoxypsoralen (8-MOP) on antioxidant response element (ARE)-regulated gene expression in mammalian cells. Lower minimal phototoxic doses (MPD) (P=0·022) and higher serum 8-MOP concentrations (P=0·052) were seen in GSTM1-null allele homozygotes compared with patients with one or two active alleles. In a subset of patients with psoriasis (n=50), the GSTM1 genotype was not associated with PUVA outcomes, although MPD [hazard ratio (HR) 1·37; 95% confidence interval (CI) for HR 1·15-1·64] and GSTT1-null (HR 2·39; 95% CI for HR 1·31-4·35) and GSTP1b (HR 1·96; 95% CI for HR 1·10-3·51) genotypes were associated with clearance of psoriasis in this patient group. Exposure of mammalian cells to 8-MOP induced gene expression via the ARE, a regulatory sequence in promoters of cytoprotective genes including GSTs, suggesting that these genes may be implicated in 8-MOP metabolism. The polymorphic human GSTs are associated with PUVA sensitivity. Further studies are required to examine the clinical relevance of these preliminary findings.

Investigation of the effect of low power laser used in photodynamic therapy for treatment of psoriasis

AbstractThe objective of this study was to investigate the effect of power on low-level lasers used in photodynamic therapy (PDT) to treat chronic plaque psoriasis in a group of Sudanese patients.Twenty-four patients with chronic plaque psoriasis were randomly selected to enter this study from a total of 100 patients who attended the Khartoum Dermatology Teaching Hospital between 2010 and 2011. The lasers used for PDT were three continuous wave diode lasers in the red portion of the electromagnetic spectrum (671–675 nm) with output powers of 16, 50 and 100 mW to activate the chemical photosensitizer (LevulanThis study showed that 62% of the patients treated with 100 mW achieved complete clearance compared with 25% for those treated with 50 mW and 0% for those treated with 16 mW.The results showed that increasing the power of low-level laser in PDT increased the clearance of plaque psoriasis. PDT can be used as an alternative method for treatment of psoriasis.