Refractory Psoriasis Research Articles

Safety and Efficacy of Combination Therapy of Upadacitinib and Biologic Agents for Treatment-Resistant Psoriasis and Psoriatic Arthritis

Importance: Although there are many available treatments for psoriasis and psoriatic arthritis (PsA), there are patients resistant to standard conventional therapy. For these patients, combination therapy of biologic agents and upadacitinib may be a viable alternative option; however, there is limited data on concomitant usage. Objective: To evaluate the safety and efficacy of combination therapy of upadacitinib and biologic agents for the treatment of refractory psoriasis and psoriatic arthritis. Design: We report the results of a retrospective chart review of 3 patients in a single practice treated with a combination of upadacitinib and biologics for psoriasis and PsA. The risks, benefits, and safety warnings of combination therapy of upadacitinib and biologic agents were discussed before initiation. After shared decision-making with the provider, patients were placed on a trial of combination therapy. Results: All three patients, previously refractory to monotherapy, experienced significant improvement of their symptoms while on combination therapy. No adverse reactions (malignancy, cardiovascular events, venous thromboembolism) occurred during treatment. However, one patient experienced a shingles outbreak and diverticulitis while on combination treatment. Further studies are needed to determine long-term efficacy with a larger sample size.

Benign Prostate Hypertrophy: An Educational Ultrasound Images and Pharmacotherapy Mini-Review

Background: A benign increase in the size of prostate (Enlargement) can be asymptomatic, but it can cause symptoms resulting from pressure on the urethra, including frequency of urination, difficulty in starting urination, poor urine stream, dribbling after urination, and inability to pass urine. Ultrasonography has been used as early as 1971 for the diagnosis of prostatic enlargement. Patients and Methods: The case of a 53-year old diabetic and hypertensive male who had refractory psoriasis and developed benign enlargement is described and an educational ultrasound images are presented. Results: The patient was complaining of dribbling after micturition for few weeks. He was not having difficulty in starting urination nor complained of frequent micturition, and the urine stream was considered normal. The urinary bladder was normal, but with mild hazy wall outline. Pre-voiding volume was 248 ml, and post-voiding volume was 9 ml. Ultrasound of the prostate showed enlarged prostate with homogenous texture. Prostate volume was 36.6 ml (Normal: 25 ml). Therefore, Oral finasteride was started. Conclusion: Many medications have been used in the treatment of benign enlargement of the prostate during the 1960s, 1970s, and 1980s, including progestational agents, Amino acids, spironolactone, candicidin, nystatin, flutamide, bromocriptine, alpha-adrenergic blockers, Serenoa repens (Saw palmetto extracts), and mepartricin. However, the current evidence-based opinion suggests that benign enlargement of the prostate can be initially treated with medications that can reduce the volume of the prostate such as finasteride and dutasteride. Tamsulosin or alfuzosin can be added to further improve lower urinary symptoms.

Inflammatory bowel disease secondary to treatment with ixekizumab in a patient with difficult-to-manage psoriasis.

Both psoriasis and inflammatory bowel disease (IBD) are immunomediated diseases. Some of their therapeutic tools are monoclonal antibodies. Ixekizumab is an interleukin-17 (IL-17) inhibitor approved for the treatment of psoriasis. Cases of IBD onset have been reported in patients treated with this drug. We present the case of a 35-year-old patient with the onset of ulcerative colitis (UC) type of IBD after starting ixekizumab treatment.

Upadacitinib Efficacy for the Treatment of Concomitant Psoriasis and Alopecia Areata

Upadacitinib is a selective JAK-1 inhibitor initially approved for the treatment of rheumatoid arthritis and recently psoriatic arthritis (PsA). We present a patient with Atopic Dermatitis (AD), Psoriasis (PsO), PsA and Alopecia Areata (AA) refractory to multiple agents however, successfully treated with upadacitinib. Our patient initially presented with refractory PsO and PsA, leading to treatment with ixekizumab. However, subsequent development of pruritic, erythematous scaly lesions, along with AA, prompted a shift to dupilumab. When distressing PsA and suboptimal outcomes with previous treatments persisted, prior biologics were discontinued and upadacitinib was initiated. Over a three-month period, the patient achieved complete clearance of PsO, significant improvement in AA and resolution of her PsA and AD. This report highlights the therapeutic benefits of upadacitinib in treating inflammatory cutaneous conditions like AA and PsO and further suggests a need for clinical trials to explore its broad therapeutic spectrum.

The Therapeutic Challenge of Treating Refractory Psoriasis: An Educational Article and Expert Opinion

Background: Therapies that are commonly used in the treatment of refractory psoriasis include mycophenolate mofetil, methotrexate, acitretin, apremilast, and tofacitinib. The medications can be used in refractory psoriasis either as monotherapy or in combination with other medications. The use of biological medications such as infliximab and etanercept in the treatment of refractory psoriasis has been increasingly reported. Patients and methods: After one month, treatment with mycophenolate and topical calcipotriol was associated with improvement in the activity of skin disease and the arthritic symptoms, but there was no significant reduction the affected area of skin. Therefore, tazarotene 0.1% cream was added. At two months of treatment, both skin and joint symptoms were slightly worsening and the patient needed a non-steroidal anti-inflammatory medication to control joint symptoms. Acitretin was added in an initial dose of 10 mg daily with intention of increasing it to 25 mg daily gradually. However, on the fourth day after adding of oral acitretin the patient reported a significant reduction in the severity of the disease and the affected area that have not achieved long time ago. The patient also reported experiencing unpleasant taste that was attributed to acitretin. Conclusion: The current expert opinion suggests that the choice of the treatment of methotrexate and mycophenolate refractory psoriasis should be based on the available evidence, and it generally depends mostly on the availability and cost of the medications, and the experience of the treating physician with the available medications. In cases of resistance to methotrexate, and mycophenolate, acitretin can be added mycophenolate, and the use of newer safe biological agents such as etanercept and Infliximab can be considered.

Tofacitinib in the treatment of recalcitrant cases of psoriasis vulgaris

Treatment of recalcitrant cases of psoriasis vulgaris can pose a major challenge to dermatologists. Despite the availability of various drugs and treatment modalities, these cases often either show unsatisfactory response to these treatments or may have to be discontinued due to development of adverse effects or may be contraindicated due to underlying morbidities. After exhausting the conventional modalities such as methotrexate, cyclosporine, acitretin, apremilast, and phototherapy, the next line of management involves usage of biologicals. Biologicals, although efficacious in most cases, come with their own set of drawbacks including cost, availability, and risk of development of anti-drug antibodies, rendering them ineffective. Furthermore, some patients have found to relapse within a few months of stopping them. We present a case series of five patients of refractory psoriasis vulgaris who had exhausted all conventional modalities (including biologicals in three of the patients) who were successfully treated with tofacitinib, a small molecule inhibiting Janus kinase 1/3 enzyme. Our patients have reported no side effects with tofacitinib till date and are continuing to maintain the results. From this series, we conclude that tofacitinib may be an effective therapy for the management of recalcitrant psoriasis.

An institution-based non-randomised prospective study to estimate the efficacy and adverse effect profile of apremilast for moderate to severe refractory palmoplantar psoriasis

Background: Psoriasis is an immune-mediated inflammatory papulo-squamous disorder presenting as chronic plaque, pustular, erythrodermic, nail, scalp, drug induced, inverse, guttate etc. Palmoplantar psoriasis causes significant functional, cosmetic and psychological disability. Apremilast is a relatively newer drug being PDE-4 inhibitor, having negligible adverse effects with minimum blood monitoring. Methods: It is an institution-based, non-randomised, prospective study conducted over a period of 3 months. 42 patients of moderate to severe disease (assessed using PPPASI), refractory to conventional line of therapy (for atleast 3 months) or had contraindications for the same were selected from our Dermatology OPD. Follow up was done monthly for 6 months. Results: 42% of the patients were good responders. 1 patient did not respond and 2 had progression of the disease. There was a decrease in the mean DLQI from a baseline of 25 to less than 15 by the end of 1st month and around 5 by the end of 6th month.60% of patients showed onset of response by the 1st month. 45% of the patients showed adverse effects, mostly being nausea followed by dizziness. Conclusions: From our study and those in the existing literature, it can be inferred that apremilast is a promising drug for palmoplantar as well as other forms of psoriasis, especially in patients with comorbidities or treatment refractory psoriasis.

Randomized study of the efficacy of monoclonal antibodies in patients with refractory psoriasis

BACKGROUND: The main vector of psoriasis therapy is suppression of proliferative activity of keratinocytes, normalization of their differentiation, neutralization of immune inflammation in the dermis and normalization of cytokine balance.
 AIM: of the study was to study the efficacy and tolerability of an IL-17A inhibitor (secukinumab) as monotherapy and in combination with methotrexate in patients with moderate and severe psoriasis vulgaris.
 MATERIALS AND METHODS: The severity of psoriasis was assessed by the Psoriasis Prevalence and Severity Index (Psoriasis Area and Severity Index, PASI). To assess the damage to the nail plates of the hands and feet in psoriasis, the NAPSI index (Nail Psoriasis Severity Index) was used. In order to assess the quality of life of patients with psoriasis, a Russian-language version of the dermatological quality of life index (DQLI) was used. Patients' quality of life was assessed before the prescribed therapy and at 12 weeks of treatment. Assessment of the severity of itching and its impact on the daily life of patients was carried out according to the Prurindex questionnaire.
 RESULTS: All patients were divided into two groups by a randomized method. The first group included 25 patients who received therapy with secukinumab in the age category of 55 (3067) years. The second group included 25 patients aged 56 (3469) years of moderate and severe psoriasis who were treated with secukinumab after initiation (300 mg) 150 mg subcutaneously in combination with methotrexate 15 mg intramuscularly for 24 weeks. Thus, in the first group PASI 90 was achieved after 24 weeks ― in 69%, PASI 100 ― in 31% patients; in the second group ― PASI 90 ― in 68%, PASI 100 ― in 32% patients respectively. In both groups, it was possible to maintain clinical remission (PASI 90) in 87.3% of patients throughout the year. During therapy in patients of both groups, there was a decrease in DLQI values from 25.63.7 to 3.53.1 (p 0.01) in the first group and from 23.33.7 up to 3.12.6 in the second group.
 CONCLUSIONS: Treatment of patients with moderate and severe psoriasis vulgaris with secukinumab has shown its high efficacy and safety. Moreover, it was estimated that the combination of secukinumab and methotrexate is comparable in effectiveness to secukinumab monotherapy. It has been established that the use of secukinumab as monotherapy and in combination with methotrexate significantly improves the quality of life of patients with moderate and severe psoriasis vulgaris.

Association of Transition of Laboratory Markers with Transition of Disease Activity in Psoriasis Patients Treated with Biologics.

Three categories of biologics-tumor necrosis factor (TNF) inhibitors, interleukin (IL) -17 inhibitors, and IL-23 inhibitors-are available for treatment of refractory psoriasis. Recent studies have shown that laboratory biomarkers such as peripheral blood neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR), and serum C-reactive protein (CRP) levels are associated with psoriasis or its severity. This study evaluated associations of transition of NLR, PLR, MLR, and CRP with transition of disease activity in psoriasis patients treated with the three categories of biologics. Data from 67 patients were analyzed. Associations of transition of psoriasis area and severity index (PASI) score with the abovementioned laboratory markers were evaluated by using a mixed effects model with PASI as the response variable, laboratory markers as fixed effects collectively, and patients as random effects. In an analysis of all the patients, serum CRP and NLR were associated with PASI score (P=0.006 and P=0.001, respectively). In patients treated with TNF inhibitors, CRP and NLR were associated with PASI score (P=0.043 and P=0.002, respectively). In patients treated with IL-17 inhibitors, NLR was associated with PASI score (P=0.001). NLR appears to be the most reliable biomarker of the effect of treatment with biologics, especially IL-17 inhibitors.

OA10 Sequential biologic usage in refractory psoriatic arthritis using ultrasound to detect psoriatic arthritis specific sub-clinical active disease

OA10 Sequential biologic usage in refractory psoriatic arthritis using ultrasound to detect psoriatic arthritis specific sub-clinical active disease

Prevalence and characterization of treatment-refractory psoriasis and super-responders to biologic treatment: a nationwide study.

Treatment with biologics often leads to clearance of psoriasis. However, some patients do repeatedly fail to respond and/or lose an achieved response (treatment refractory) to the biologic, whereas other patients achieve excellent response to one biologic and remain clear of psoriasis for several years (super-responders). To identify and characterize patients with treatment refractory psoriasis and patients who are super-responders to biologic treatment. Patients registered in DERMBIO between January 2007 and November 2019 were included. Patients were categorized as being treatment refractory if they had had treatment failure to ≥3 biologics targeting ≥2 different pathways. Super-responders were patients treated with their first biologic for minimum 5 years without an absolute psoriasis area and severity index (PASI) > 3 between 6 months and 5 years of treatment. All remaining patients from DERMBIO served as comparators. In total, 3280 patients were included with a mean age of 45.0 years. 1221 (37%) of the patients were females. Of the included patients, 214 (6.5%) were categorized as treatment refractory and 207 (6.3%) were categorized as super-responders. Treatment refractory patients had higher mean body weight (100.6 kg vs. 90.6 kg, P < 0.0001) and higher mean BMI (32.2 vs. 29.4, P < 0.0001) compared with the rest of patients in DERMBIO. Super-responders had higher socioeconomic status and fewer comorbidities compared with the comparator group (P < 0.0001). A small proportion of patients with psoriasis treated with biologics are either super-responders or treatment refractory. Treatment refractory patients have higher body weight, whereas super-responders have fewer comorbidities and higher socioeconomic status.

Real-world blood examination screening data before initiation of biologics for psoriasis patients.

Psoriasis is a chronic immune-mediated inflammatory skin disease characterized by hyperproliferation of epidermal keratinocytes. Biologics have been available for the treatment of patients with refractory psoriasis since 2010 in Japan, and as of December 2021, 10 biologics were available. The Biologics Review Committee of the Japanese Dermatological Association for Psoriasis recommends blood examination tests for antinuclear antibodies (ANA), Krebs von den Lugen (KL)-6, hepatitis B surface antigen (HBsAg), hepatitis B surface antibodies (HBsAb), hepatitis B core antibodies (HBcAb), hepatitis C virus (HCV) antibodies, HIV antibodies, human T-cell leukemia virus (HTLV)-1 antibodies, β-D-glucan, and the T-cell spot (T-SPOT) test before initiation of biologics at screening. In this study, we evaluated the use of biologics for 127 psoriasis patients and the blood examination screening data before initiation of biologics in the real-world setting. Tumor necrosis factor inhibitors, interleukin (IL)-17 inhibitors and IL-23 inhibitors were initiated for 54 (42.5%), 36 (28.3%), and 37 (29.1%) patients, respectively. The numbers of patients positive for ANA, HBsAg, HBsAb, HBcAb, HCV antibody, HIV antibody, HTLV-1 antibody, and T-SPOT were 27 (21.3%), 0 (0%), 22 (17.3%), 20 (15.7%), three (2.4%), zero (0%), one (0.8%), and 4 (3.1%), respectively. The numbers of patients whose KL-6 and β-D-glucan levels were higher than the reference values were seven (5.5%) and seven (5.5%), respectively. In the real-world setting, it is sometimes unavoidable to use biologics for those patients with abnormal data although careful monitoring is necessary.

A Case of Refractory Pustular Psoriasis Successfully Treated with Multidrug Therapy Using Brodalumab

A Case of Refractory Pustular Psoriasis Successfully Treated with Multidrug Therapy Using Brodalumab

Epidermal Hyperproliferation With Less Prominent Dermal Inflammation Is the Unique Histopathological Feature of the Refractory Lesions in Psoriasis Treated With Ustekinumab.

Although ustekinumab (UST) shows excellent efficacy in treating psoriasis, not all patients have a complete clearance rate. The purpose of this study was to investigate the histopathological characteristics of refractory psoriasis lesions in patients with excellent response to UST. Fifty-seven patients with newly diagnosed psoriasis and 66 patients with a 75% reduction in the Psoriasis Area and Severity Index score after UST treatment were included. Computer-aided image analysis was performed to measure the epidermal thickness, horny layer thickness, number of dermal vessels, and dermal inflammatory cell infiltration rate. Parakeratosis was scored using a 4-point scale. These measurements were compared between the refractory lesions of UST-treated patients and the untreated lesions of newly diagnosed patients after the adjustment for confounding factors. The dermal inflammatory cell infiltration rate was significantly lower in the refractory lesions (P = 0.022). Meanwhile, the epidermal thickness, horny layer thickness, grade of parakeratosis, and dermal vessel count did not differ between the groups (P = 0.125, 0.719, 0.542, and 0.758, respectively). Subgroup analyses were performed within the UST-treated group after dividing them into 2 groups according to the number of treatments or treatment response rates. None of these features were significantly different between the subgroups. This study suggests that the reduction of dermal inflammation by UST was not sufficient to ameliorate the epidermal changes and implies the role of the interleukin-23-independent downstream cytokine pathway in causing the refractory lesions among patients who responded well to UST. The continuation of UST treatment might not further improve epidermal alterations.

Successful ustekinumab treatment of severe refractory psoriasis vulgaris in a hemodialysis patient.

article: Successful ustekinumab treatment of severe refractory psoriasis vulgaris in a hemodialysis patient - Italian Journal of Dermatology and Venereology 2021 August;156(4):510-1 - Minerva Medica - Journals

Refractory Pediatric Psoriasis and Atopic Dermatitis: The Importance of Therapeutical Adherence and Biological Management.

The rates of refractory pediatric psoriasis and atopic dermatitis (AD) have steadily risen over the last few decades, demanding newer and more effective therapies. This review aims to explore the reasons for resistant disease, as well as its management; this includes the indications for, efficacy of, and safety of current therapies for refractory pediatric dermatologic disease. A PubMed search for key phrases was performed. Poor medication adherence is the most common cause of resistant disease and may be managed with techniques such as simplified treatment regimens, more follow-ups and educational workshops, as well as framing and tailoring. Once problems with adherence are ruled out, escalating treatment to stronger biologic therapy may be indicated. Development of anti-drug antibodies (ADAs) can cause patients’ disease to be refractory in the presence of potent biologics, which may be addressed with regular medication use or concomitant methotrexate. If patients with AD fail to respond to biologic therapy, a biopsy to rule out mycosis fungoides, or patch testing to rule out allergic contact dermatitis, may be indicated. A limitation of this study is the absence of more techniques for the management of poor medication adherence. Managing medication adherence, escalating treatment when appropriate, and addressing possible anti-drug antibodies will help assure control and relief for patients with resistant disease.

Management of psoriasis with biologics in clinical practice: an update for 2020.

This article aims to address updates on recent clinical trial findings (April 2019 to April 2020) regarding biologic therapy initiation and maintenance for adult patients. Prescribers should use this update as guidance for determining the appropriate biologic class based on patient characteristics and for approaching biologic-experienced patients with refractory psoriasis. This update also may serve as a reference for the recommended dosing regimens of the 11 approved biologics.

Promising results with secukinumab in refractory pediatric psoriasis

Promising results with secukinumab in refractory pediatric psoriasis

Use of the IL-17 inhibitor ixekizumab in a case of refractory pediatric psoriasis and a summary of FDA-approved biologics for moderate to severe pediatric psoriasis vulgaris

Use of the IL-17 inhibitor ixekizumab in a case of refractory pediatric psoriasis and a summary of FDA-approved biologics for moderate to severe pediatric psoriasis vulgaris

Sarcoid- like Phenomenon - ustekinumab induced granulomatous reaction mimicking diffuse metastatic disease: a case report and review of the literature

BackgroundThe utilization of monoclonal antibodies has become more widespread over the past decade. However, the development of non-caseating granulomas with the use of monoclonal antibodies, such as ustekinumab, is not widely reported in the literature.Case presentationWe report a case of a 50-year-old Caucasian male who presented complaining of weight loss and shortness of breath. He was receiving ustekinumab for refractory psoriasis but had no other significant medical comorbidities. On physical examination, reduced breath sounds on the right side were noted. Blood cultures were drawn on presentation and came back negative in 48 hours. A chest computed tomography scan revealed a large right lung mass in addition to right-sided pleural effusion. Therapeutic thoracocentesis was done; fluid cytology and analysis were negative for malignancy, acid-fast bacilli, or fungal infections. A positron emission tomography scan showed multifocal radiotracer uptake including within right lung mass, multiple bones, lymph nodes, liver and spleen. Biopsies showed hyalinized non-necrotizing granulomas. Immunohistochemical stains for AE1/AE3, cytokeratin 7 and 20, and thyroid transcription factor 1, were all negative. He was started on steroid therapy, and ustekinumab was discontinued and the follow-up computed tomography after a few months showed substantial improvement. However, over the course of next 4 months patient developed hepatic dysfunction and recurrent ascites and ultimately underwent transjugular intrahepatic portosystemic shunt placement. Furthermore, he was started on azathioprine and steroids were tapered. He improved clinically and was discharged from our hospital within a week.ConclusionsThis case highlights the need for careful consideration of patient medication history while evaluating the possible differential diagnoses that may contribute to a patient’s presentation.