ABSTRACT
Systemic lupus erythematosus (SLE) is an autoimmune rheumatic condition characterized by an unpredictable course and a wide spectrum of manifestations varying in severity. Individuals with SLE are at an increased risk of cerebrovascular events, particularly strokes. These strokes manifest with a diverse range of symptoms that cannot be solely attributed to conventional risk factors, underscoring their significance among the atypical risk factors in the context of SLE. This complexity complicates the identification of optimal management plans and the selection of medication combinations for individual patients. This susceptibility is further complicated by the nuances of neuropsychiatric SLE, which reveals a diverse array of neurological symptoms, particularly those associated with ischemic and hemorrhagic strokes. Given the broad range of clinical presentations and associated risks linking strokes to SLE, ongoing research and comprehensive care strategies are essential. These efforts are critical for improving patient outcomes by optimizing management strategies and discovering new medications. This review aims to elucidate the pathological connection between SLE and strokes by examining neurological manifestations, risk factors, mechanisms, prediction and prevention strategies, management plans, and available research tools and animal models. It seeks to explore this medical correlation and discover new medication options that can be tailored to individual SLE patients at risk of stroke.
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Growing evidence suggests that alterations in the gut microbiome impact the development of inflammatory bowel diseases (IBDs), including Crohn's disease (CD) and ulcerative colitis (UC). Although IBD often requires the use of immunosuppressant drugs and biologic therapies to facilitate clinical remission and mucosal healing, some patients do not benefit from these drugs, and the reasons for this remain poorly understood. Despite advancements, there is still a need to develop biomarkers to help predict prognosis and guide treatment decisions. The aim of this study was to investigate the gut microbiome of IBD patients using biologics to identify microbial signatures associated with responses, following standard accepted criteria. Microbiomes in 66 stool samples from 39 IBD patients, comprising 20 CD and 19 UC patients starting biologic therapies, and 29 samples from healthy controls (HCs) were prospectively analyzed via NGS and an ensemble of metagenomics analysis tools. At baseline, differences were observed in alpha and beta metrics among patients with CD, UC and HC, as well as between the CD and UC groups. The degree of dysbiosis was more pronounced in CD patients, and those with dysbiosis exhibited a limited response to biological drugs. Pairwise differential abundance analyses revealed an increasing trend in the abundance of an unannotated genus from the Clostridiales order, Gemmiger genus and an unannotated genus from the Rikenellaceae family, which were consistently identified in greater abundance in HC. The Clostridium genus was more abundant in CD patients. At baseline, a greater abundance of the Odoribacter and Ruminococcus genera was found in IBD patients who responded to biologics at 14 weeks, whereas a genus identified as SMB53 was more enriched at 52 weeks. The Collinsella genus showed a higher prevalence among non-responder IBD patients. Additionally, a greater abundance of an unclassified genus from the Barnesiellaceae family and one from Lachnospiraceae was observed in IBD patients responding to Vedolizumab at 14 weeks. Our analyses showed global microbial diversity, mainly in CD. This indicated the absence or depletion of key taxa responsible for producing short-chain fatty acids (SCFAs). We also identified an abundance of pathobiont microbes in IBD patients at baseline, particularly in non-responders to biologic therapies. Furthermore, specific bacteria-producing SCFAs were abundant in patients responding to biologics and in those responding to Vedolizumab.
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BACKGROUND: In patients with severe, uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP), dupilumab 300â¯mg every 2 weeks can completely resolve nasal polys, sinus disease, and symptoms. In this case, patients ask for de-escalation. Although trials have demonstrated recurrence after stopping the biologic at 24 weeks, reducing the dose of dupilumab to once every 4 weeks did not result in deterioration of control. An extension of the treatment intervals would, however, diverge from the approval text, and is currently not recommended. METHODS: The course of 29 patients with severe CRSwNP, type2 inflammation-associated comorbidities, and an indication for biologic was retrospectively analyzed. After resolution of CRSwNP and symptoms under biweekly dupilumab 300â¯mg, the dupilumab interval had been prolonged individually, initially up to 4 weeks, thereafter up to 6 weeks, if applicable. Control was assessed via quality of life (22-item sinonasal outcome test, SNOT-22), nasal polyp score, and smell identification test (Sniffin' Sticks; Burghart Messtechnik, Holm, Germany). RESULTS: All patients showed an excellent improvement within the first 3 months. The dupilumab application interval was extended to 4 weeks after 7-31 months (median 13 months) and to 6 weeks (nâ¯= 9) after 17-35 months (median 23 months). No recurrent polyps or symptoms were subsequently observed. CONCLUSION: In case of maximal regression of polyps and discomfort, extension of dupilumab injection intervals to 4 and potentially 6 weeks is possible without clinical worsening. Further studies on de-escalation or termination of biologic treatment when CRSwNP control is achieved are essential.
Subject(s)
Antibodies, Monoclonal, Humanized , Nasal Polyps , Rhinitis , Sinusitis , Humans , Nasal Polyps/drug therapy , Nasal Polyps/complications , Sinusitis/drug therapy , Sinusitis/complications , Antibodies, Monoclonal, Humanized/therapeutic use , Rhinitis/drug therapy , Rhinitis/complications , Chronic Disease , Male , Female , Treatment Outcome , Middle Aged , Adult , Drug Administration Schedule , Aged , Retrospective Studies , RhinosinusitisABSTRACT
Background: Etrolizumab is a promising drug for treating moderate to severe ulcerative colitis. Aim: The aim of this study was to assess the efficacy and safety of etrolizumab for induction and maintenance of remission in moderate to severe ulcerative colitis. Methods: We searched the following databases: PUBMED, Web of Science, OVID, and SCOPUS from inception to January 15. Inclusion criteria were any phase 2 and 3 clinical trials that compared etrolizumab with a placebo in treating moderate to severe ulcerative colitis, excluding case reports, animal studies, phase 1 trials, and conference abstracts due to duplication. We used RevMan software (5.4) for the meta-analysis. Results: Five clinical trials were included in our meta-analysis. The total number of patients included in the study is 1248 patients, 860 patients in the etrolizumab group and 388 patients in the placebo group. In the induction phase, the pooled analyses showed a statistically significant association between etrolizumab and increased clinical remission, and endoscopic remission compared with placebo (risk ratio [RR] = 2.66, 95% confidence interval [CI] = 1.69-4.19, p < 0.0001), and (RR = 2.35, 95% CI = 1.52-3.65, p = 0.0001), respectively. In the maintenance phase, the pooled analyses showed a statistically significant association between etrolizumab and increased histologic remission and endoscopic remission (RR = 2.04, 95% CI = 1.40-2.98, p = 0.0002) and (RR = 1.92, 95% CI = 1.29-2.85, p = 0.001), respectively. No statistically significant difference was observed in adverse events between etrolizumab and placebo in the induction and maintenance phases. Conclusion: Our results show that etrolizumab is an effective and safe drug for the induction and maintenance of clinical remission in moderate to severe ulcerative colitis patients, as proved by histologic and endoscopic findings. Future randomized trials are still needed to compare etrolizumab to the other agents and further establish its value for the practice.
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The global burden of inflammatory bowel diseases (IBD) is estimated at 4.9 million and the global prevalence exceeds 0.3%. Multiple newer therapeutic agents have broadened the options for the therapy of IBD in the last three decades. Thiopurines, however, have retained their place as maintenance therapy in IBD, especially in resource-constrained setting. But thiopurines have narrow therapeutic range, often needing discontinuation due to side effects or lack of efficacy. Biologic agents revolutionized the treatment of IBD, but the efficacy is lost in 50% of patient after one year. These outcomes are often due to inadequate drug concentrations that may lead to the development of antibodies as well as pharmacodynamic failure. Therapeutic drug monitoring (TDM) was proposed to reduce loss of response and to optimize the therapy in patients on thiopurine and biologic therapy. TDM is based on exposure-response relationship, suggesting a positive correlation between elevated serum anti-TNF concentrations and favorable therapeutic outcomes. TDM has multiple facets. This article discusses the benefits, evidence and limitations of TDM. The practical use of TDM in clinical practice is highlighted. Newer developments in the field and their relevance in practice are discussed.
Subject(s)
Inflammatory Bowel Diseases , Tumor Necrosis Factor Inhibitors , Humans , Tumor Necrosis Factor Inhibitors/therapeutic use , Drug Monitoring , Antibodies , Purines/therapeutic use , Inflammatory Bowel Diseases/epidemiologyABSTRACT
Psoriasis is an immune-mediated chronic inflammatory skin disease that affects 2% to 3% of the world's population. It is widely assumed that immune cells and cytokines acting together play a crucial part in the pathophysiology of psoriasis by promoting the excessive proliferation of skin keratinocytes and inflammatory infiltration. Interleukins (ILs), as a critical component of cytokines, have been closely associated with the pathogenesis and progression of psoriasis. This review summarizes the current contribution of ILs to psoriasis and describes the role each IL performs in psoriasis. Furthermore, the paper presents the therapeutic effects and application prospects of biologics developed for ILs in clinical treatment and experiments. The study aims to further the research on ILs in the treatment of psoriasis.
Subject(s)
Interleukins , Psoriasis , Humans , Psoriasis/drug therapy , Psoriasis/pathology , Skin/pathology , Keratinocytes/pathology , CytokinesABSTRACT
Pyoderma gangrenosum (PG) is an uncommon inflammatory dermatological disorder characterized by painful ulcers that quickly spread peripherally. The pathophysiology of PG is not fully understood; however, it is most commonly considered a disease in the spectrum of neutrophilic dermatoses. The treatment of PG remains challenging due to the lack of generally accepted therapeutic guidelines. Existing therapeutic methods focus on limiting inflammation through the use of immunosuppressive and immunomodulatory therapies. Recently, several reports have indicated the successful use of biologic drugs and small molecules administered for coexisting diseases, resulting in ulcer healing. In this review, we summarize the discoveries regarding the pathophysiology of PG and present treatment options to raise awareness and improve the management of this rare entity.
Subject(s)
Biological Products , Pyoderma Gangrenosum , Humans , Pyoderma Gangrenosum/drug therapy , Immunosuppressive Agents/therapeutic use , Inflammation/drug therapy , Biological Products/therapeutic use , ImmunomodulationABSTRACT
BACKGROUND/OBJECTIVES: The aim of the study is to assess the effect of juvenile idiopathic arthritis (JIA) and biologic disease-modifying anti-rheumatic drugs (bDMARDs) on ovarian reserve in children. MATERIALS AND METHODS: A cross-sectional study was performed from March 2021 to March 2022 and included 81 patients with JIA and 49 healthy children. Serum anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol levels were analyzed using electrochemiluminescence methods. RESULTS: The mean of current age (13.5 ± 3.2 vs. 14.4 ± 2.4 years), height standard deviation score (SDS) (- 0.35 ± 1.18 vs. - 0.44 ± 0.94), body mass index SDS (0.12 ± 1.33 vs. 0.25 ± 1.28), and the median weight SDS (- 0.13 (- 2.27-3.23) vs. - 0.52 (- 3.4-3.3)) were similar in JIA patients and controls (p > 0.05). Patients with JIA were divided into two groups according to their treatment regimens: treated with methotrexate (MTX) (biologic naive) (n = 32) and treated with MTX plus bDMARDs (n = 49). No significant differences were detected between the 3 groups regarding menarche age, menstrual cycle length, and flow duration (for all p > 0.05). The median serum concentration of AMH was 2.94 (1.12-7.88) ng/ml in the control group, 3.02 (0.36-8.54) ng/ml in the biologic naïve group, and 3.01 (0.99-8.26) ng/ml in the MTX plus bDMARD group. There were no significant differences between 3 groups according to serum AMH, FSH, LH, and estradiol levels (p > 0.05). CONCLUSION: Biologic DMARDs are reassuring in terms of ovarian reserve in girls with JIA and demonstrate that AMH is unaffected by treatment. Prospective studies with larger sample sizes are needed to confirm our findings and to evaluate the impact on the future fertility of patients. Key Points ⢠Although biologic disease-modifying anti-rheumatic drugs (bDMARDs) are being game-changing treatment options in juvenile idiopathic arthritis, their effect on fertility and ovarian reserve is one of the most discussed issues. ⢠In addition to treatment used, autoimmune diseases might also have a negative effect on fertility. ⢠In this cross-sectional study, we found that anti-Mullerian hormone level of patients who were on bDMARDs, patients who were on methotrexate, and healthy controls were similar. ⢠Our results suggest that bDMARDs are reassuring in terms of ovarian reserve in girls with JIA and demonstrate that AMH is unaffected by treatment.
Subject(s)
Antirheumatic Agents , Arthritis, Juvenile , Biological Products , Ovarian Reserve , Female , Child , Humans , Arthritis, Juvenile/drug therapy , Methotrexate/pharmacology , Cross-Sectional Studies , Anti-Mullerian Hormone , Prospective Studies , Luteinizing Hormone , Follicle Stimulating Hormone , Antirheumatic Agents/therapeutic use , Antirheumatic Agents/pharmacology , Estradiol/pharmacologyABSTRACT
PURPOSE: Historically managed with intranasal corticosteroids (INCS) and endoscopic sinus surgery (ESS), type-2 Chronic RhinoSinusitis with Nasal Polyps (CRSwNP) treatment was revolutionized by the introduction of dupilumab but universally accepted guidelines are still lacking. METHODS: Patients treated at our University Hospital for type-2 CRSwNP were enrolled. Demographic data were collected, as well as laboratory (eosinophils, total IgE), endoscopic [nasal polyps score (NPS), modified Lund-Kennedy score (mLKS)], radiological [Lund-Mackay score (LMS) at CT scan], SNOT-22, and olfactory [Sniffin' Sticks identification test (SSIT)] features. Patients were treated with dupilumab or ESS and re-evaluated after 3 and 12 months. RESULTS: At 3 and 12 months, patients undergoing ESS achieved a higher reduction of NPS and mLKS, while patients receiving dupilumab experienced a higher improvement at SNOT-22 and SSIT with a greater positive variation in the prevalence of anosmia (- 57.7% vs - 42.9%) and normosmia (+ 37.8 vs + 28.5%). Mean mLKS and LMS were quite similar. Results were independent of clinical features known to contribute to CRSwNP severity, except for patients with ≥ 2 prior ESS who had a significantly lower smell improvement. CONCLUSION: ESS and dupilumab were effective at reducing CRSwNP inflammatory burning. CRSwNP smell impairment cannot be attributed only to olfactory cleft obstruction and other mechanisms may be involved. Dupilumab acts systemically with poor correlation with NPS. As of today, dupilumab appears to be more suitable for elderly patients with anesthesiological contraindications and/or several previous surgeries, while ESS may represent the first-line choice in surgery-naive patients.
Subject(s)
Antibodies, Monoclonal, Humanized , Nasal Polyps , Rhinitis , Rhinosinusitis , Sinusitis , Humans , Aged , Nasal Polyps/complications , Nasal Polyps/drug therapy , Nasal Polyps/surgery , Rhinitis/complications , Rhinitis/drug therapy , Rhinitis/surgery , Sinusitis/complications , Sinusitis/drug therapy , Sinusitis/surgery , Chronic Disease , Quality of LifeABSTRACT
Dupilumab-induced hypereosinophilia is mediated by blockade of the IL-4/IL-13 pathway, which reduces eosinophil migration from peripheral blood. The increase in peripheral blood eosinophils may lead to chronic eosinophilic pneumonia (CEP) and/or eosinophilic granulomatosis with polyangiitis, but a direct causal connection between dupilumab and eosinophilic lung diseases has not been established. A 33-year-old Japanese woman with bronchial asthma since age three was treated with fluticasone propionate plus salmeterol twice daily after several asthma exacerbations at age 17. Her course was complicated by CEP at age 33 which resolved without the need for systemic steroids. However, in the four months following resolution of her CEP, the patient had three asthma exacerbations, and a recurrence of CEP, with blood leukocytes of 8500/µL, of which 25.0% were eosinophils. She was treated with prednisolone 50 mg/day, but she could not continue this dose due to the onset of myalgia. Then she had relapsing CEP twice within three months. She was treated with prednisolone 15 mg/day for CEP, but she had persistent asthma for more than one month; dupilumab was added at 600 mg, followed by 300 mg every two weeks. In the first month of treatment with dupilumab, the patient's asthma symptoms resolved completely, and she had only one relapse of CEP. In 12 months of follow-up, she had neither an asthma exacerbation nor another relapse of CEP. Dupilumab may be a promising treatment for patients with refractory asthma complicated by recurring CEP and undesirable steroid side effects.
Subject(s)
Asthma , Churg-Strauss Syndrome , Granulomatosis with Polyangiitis , Pulmonary Eosinophilia , Humans , Female , Adolescent , Adult , Pulmonary Eosinophilia/drug therapy , Pulmonary Eosinophilia/complications , Pulmonary Eosinophilia/diagnosis , Churg-Strauss Syndrome/complications , Churg-Strauss Syndrome/drug therapy , Granulomatosis with Polyangiitis/complications , Asthma/drug therapy , Asthma/complications , Prednisolone/therapeutic use , Chronic Disease , Recurrence , Fluticasone-Salmeterol Drug Combination/therapeutic useABSTRACT
Background: Although it is a truism that drugs benefit patients only when taken, surprisingly little is known about real-world drug-use persistence and discontinuation, even for expensive biologic drugs. Methods: We used longitudinal self-reported drug-use data from the inflammatory bowel disease (IBD) Partners registry of people with IBD to construct Kaplan-Meier drug-use persistency graphs for biologic drug-use spans that started between 2017 and 2022. Results: We examined 2034 drug-use spans for 1594 survey participants. Most of the biologic drugs had a 75%+ persistency rate around the one-year mark and 60%+ persistency at the 3-year mark. The overall persistency and the differences in persistency between drugs were aligned with published literature. Conclusions: This analysis demonstrates the feasibility of collecting IBD-specific patient-reported drug persistency data via a voluntary patient registry. Patient-reported persistency provides real-world drug persistency data and the patient's perspectives as to why they discontinued use of the drug-a combination of data and perspective that is not available from any other real-world medical record, claim, and pharmacy data source that are valuable to physician, patients, payers, healthcare policymakers, and health technology assessment organizations.
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Conventional therapy is the most commonly used treatment for Crohn's disease (CD), but it does not always achieve disease control, which is why the use of biologic drugs is increasing. The aim of this study was to analyze the efficacy and safety of biologic drugs in adult patients diagnosed with moderate-severe CD. An intensive search was performed in PubMed, Web of Science and Medline to collect phase 2 or 3 clinical trials published between 2018 and 2023 that were randomized, placebo-controlled and double-blind trials analyzing the efficacy and safety of biologic drugs in adult patients diagnosed with CD. This systematic review was conducted according to the PRISMA statement. Thirteen clinical trials evaluating eight biologic drugs were included. Upadacitinib, vedolizumab, adalimumab, guselkumab, mirikizumab, ustekinumab and risankizumab showed statistically significant efficacy across different clinical, endoscopic, histological, genetic, biomarker or quality-of-life parameters. However, PF-00547659 only showed statistically significant results for the CDAI-70 at week 12. In terms of safety, the incidence and severity of adverse effects were analyzed, with all drugs being well tolerated and presenting a good safety profile since most adverse effects were mild. Biologic drugs can be considered an effective and safe option for the treatment of moderate-severe CD in adult patients with an inadequate response or intolerance to conventional therapy.
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Background: Recent knowledge of psoriasis pathogenesis has led to the development of selective drugs. Among these, brodalumab is a monoclonal antibody targeting the interleukin (IL)-17A receptor approved for the treatment of moderate-to-severe plaque psoriasis. Biologics may be considered in patients with milder diseases in case of active psoriatic arthritis, severe impact on patient's quality of life, and involvement of sensitive and difficult-to-treat areas. These skin locations commonly require systemic drugs. Recently, psoriasis severity monitoring has also changed. Indeed, the clinical evaluation by means of specific efficacy scores was combined with serological evaluation by means of the assay of specific inflammatory biomarkers. Methods: An observational study enrolled patients affected by moderate-to-severe plaque psoriasis involving difficult-to-treat areas, undergoing treatment with brodalumab to evaluate the effectiveness and safety of brodalumab in patients with psoriasis affecting difficult-to-treat areas (scalp and palmoplantar regions). Secondary outcomes were the assessment of the development of serum markers of inflammation during the treatment period as well as the evaluation of the dermoscopic features of the affected sites to quantify disease activity and response to treatment. Results: Twenty-five patients were included in the study. A statistically significant reduction from baseline in PASI, PSSI, ppPASI and DLQI values as early as week 24 was observed, with further improvement up to week 52. Plasma levels of MMP-3, VEGF-A, and hs-PCR decreased during treatment from week 0 to week 52. Conclusion: Our real-life experience suggests brodalumab as a valuable option for the management of psoriasis located in difficult-to-treat areas. Moreover, our study highlights that the use of brodalumab reduces the plasmatic levels of inflammatory biomarkers (MMP-3, VEGF-A and hs-PCR), showing how the drug modulates the skin inflammatory response by reducing systemic inflammation.
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In recent years, identifying the pathophysiologic mechanisms underlying autoimmune arthritides and systematic diseases has led to the use of biological drugs. The primary targets of those biological therapies are cytokines, B cells, and co-stimulation molecules. So far, these targeted therapies have shown good clinical improvement and an acceptable toxicity profile. However, by blocking components of an intact immune system, autoimmune phenomena and paradoxical inflammation have emerged, and among them many cutaneous immune-related adverse events (irAEs). In this article, we review the current state of knowledge on the clinical features and mechanisms of specific cutaneous irAEs observed during treatment with biological therapies. Among those, psoriatic skin lesions are the most commonly observed. Herein, we also report new cases of cutaneous irAEs recently seen in our clinic to help physicians treating inflammatory arthritides recognize cutaneous irAEs early and better manage patients receiving biologic therapies.
Subject(s)
Arthritis , Neoplasms , Humans , Biological Therapy/adverse effects , Skin , Cytokines , Neoplasms/drug therapyABSTRACT
Psoriasis is a chronic, immune-mediated inflammatory disease with a worldwide prevalence ranging between 0.51 and 11.43%. It results in a large clinical and social burden, with patients frequently suffering from reduced quality of life, psychologic distress and debilitating comorbidities. Biologic agents are used to establish and maintain disease control in patients with moderate-to-severe psoriasis and are essential to improving quality of life. However, a substantial proportion of patients have limited access to therapy due to economics, health policies and clinical considerations, which creates clinical unmet needs that disadvantage both patients and healthcare professionals. Biosimilars are a cost-effective alternative to off-patent biologic therapies, and there is mounting evidence to suggest they offer a valuable pharmacoeconomic strategy to lower healthcare costs in patients with psoriasis. Furthermore, the introduction of biosimilars can increase the number of patients able to receive biologics, allowing these patients to be treated earlier in the disease course, potentially modifying the course of their disease and reducing the risk of comorbidities. In time, the emergence of additional data, particularly those related to long-term safety, efficacy in extrapolated indications and the effects of switching, should reassure physicians and help overcome the final hurdles for a wider implementation of biosimilars. This review aims to provide an overview of current treatment approaches for patients with moderate-to-severe psoriasis in the biosimilars era and explores both the current challenges and potential opportunities to improve access to high-quality, effective treatments.
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Background: Pharmacotherapy with biologics and small molecules, as the more effective therapies for moderate to severe ulcerative colitis (UC) and Crohn's disease (CD), is complex. Choosing the best methods for their utilization in order to induce and maintain remission are critical for practicing gastroenterologists. We aimed to develop an Iranian consensus on the management of inflammatory bowel disease (IBD) patients with biologics and small molecules. Methods: A Delphi consensus was undertaken by experts who performed a literature summary and voting process. Quality of evidence was assessed using the Grading and Recommendations Assessment, Development, and Evaluation; and an additional risk of bias-protocol. Results: Following an extensive search of the literature, 219 studies were used to determine the quality of the evidence. After three rounds of voting, consensus (defined as≥80% agreement) was reached for 87 statements. Conclusion: We considered different aspects of pharmacotherapy in this consensus. This guideline, along with clinical judgment, can be used to optimize management of IBD patients.
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Erythrodermic psoriasis (EP) is a severe and rare variant of psoriasis (less than 3% of cases), characterized by generalized scaling and erythema affecting more than 90% of body surface area. Several systemic symptoms can be present in patients with EP such as lymphadenopathy, arthralgia, fever, fatigue, dehydration, serum electrolyte disturbances, and tachycardia making this condition a possible life-threatening disease, particularly if appropriate treatments are not performed. In this scenario, effective and safe therapies are required. Unfortunately, the rarity of EP makes head-to-head Phase III trials challenging, leading to the lack of established guidelines for its management. Globally, conventional systemic drugs such as cyclosporine, methotrexate, and retinoids often have contraindications linked to patients' comorbidities and have not shown a high profile of efficacy and safety. Recently, the development of biologic drugs including anti-tumor necrosis factor-α and anti-interleukin 12-23, 23, and 17 has revealed favorable results for the management of plaque psoriasis, making them also a possible therapeutic option for EP disease. However, their use in EP is still off-label. The aim of our study was to review current literature on the use of biologic drugs for the treatment of EPs in order to offer a wide perspective on their possible application in EP management.
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Generalized pustular psoriasis (GPP) is a severe and rare form of psoriasis, being a potentially life-threatening condition, characterized by recurring episodes or flares of widespread cutaneous erythema with macroscopic sterile pustules. An irregular innate immune response is linked to GPP, which is considered an auto-inflammatory disorder, while innate and adaptive immunopathogenic responses are involved in psoriasis pathogenesis. In consequence, different cytokine cascades have been suggested to be mainly involved in the pathogenesis of each different psoriasis form, with the interleukin (IL)23/IL17 axis implied in plaque psoriasis, and the IL36 pathway in the GPP. As regards GPP treatment, conventional systemic drugs available for plaque psoriasis are usually used as the first-line treatment option. However, contraindications and adverse events often limit the use of these therapies. In this scenario, biologic drugs may represent a promising treatment option. To date, even if 12 different biologics have been approved for plaque psoriasis, none of these is approved for GPP where they are employed off-label. Recently, spesolimab, an anti-IL36 receptor monoclonal antibody, has been recently approved for GPP. The purpose of this article is to assess the current literature about the use of biological therapies for the treatment of GPP to establish the basis for a shared GPP management algorithm.
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Chronic inflammatory diseases of the lung are some of the leading causes of mortality and significant morbidity worldwide. Despite the tremendous burden these conditions put on global healthcare, treatment options for most of these diseases remain scarce. Inhaled corticosteroids and beta-adrenergic agonists, while effective for symptom control and widely available, are linked to severe and progressive side effects, affecting long-term patient compliance. Biologic drugs, in particular peptide inhibitors and monoclonal antibodies show promise as therapeutics for chronic pulmonary diseases. Peptide inhibitor-based treatments have already been proposed for a range of diseases, including infectious disease, cancers and even Alzheimer disease, while monoclonal antibodies have already been implemented as therapeutics for a range of conditions. Several biologic agents are currently being developed for the treatment of asthma, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis and pulmonary sarcoidosis. This article is a review of the biologics already employed in the treatment of chronic inflammatory pulmonary diseases and recent progress in the development of the most promising of those treatments, with particular focus on randomised clinical trial outcomes.
Subject(s)
Biological Products , Pulmonary Disease, Chronic Obstructive , Humans , Biological Products/therapeutic use , Administration, Inhalation , Pulmonary Disease, Chronic Obstructive/drug therapy , Chronic Disease , Lung , Antibodies, Monoclonal/therapeutic useABSTRACT
BACKGROUND: Inflammatory bowel diseases (IBDs), including ulcerative colitis (UC) and Crohn's disease (CD), are chronic and disabling diseases that affect patient health-related quality of life (HRQoL). IBD patients are frequently exposed to high levels of stress and psychological distress. Biological drugs have been proven to reduce inflammation, hospitalization, and most of the complications that characterize IBDs; their potential contribution to patients' HRQoL remains to be explored. AIM: To evaluate and compare any change in the HRQoL and markers of inflammation in IBD patients undergoing biological drugs (infliximab or vedolizumab). MATERIAL AND METHODS: A prospective observational study was conducted on a cohort of IBD patients, aged >18 years, who were prescribed with infliximab or vedolizumab. Demographic and disease-related data at baseline were collected. Standard hematological and clinical biochemistry parameters, including C-reactive protein (CRP), white blood cells count (WBC), erythrocytes sedimentation rate (ESR), and α1 and α2 globulins were measured after a 12-h fast at baseline (T0), after 6 weeks (T1), and at 14 weeks (T2) of biological treatment. Steroid use, disease activity as measured by the Harvey-Bradshaw index (HBI) and partial Mayo score (pMS) for the CD and UC, respectively, were also recorded at each timepoint. The Short Form 36 Health Survey (SF-36), Functional Assessment of Chronic Illness Therapy (FACIT-F), and Work Productivity and Activity Impairment-General Health Questionnaire (WPAI:GH) were administered to each patient at baseline, T1, and T2 to address the study aims. RESULTS: Fifty eligible consecutive patients (52% with CD and 48% with UC) were included in the study. Twenty-two patients received infliximab and twenty-eight received vedolizumab. We noted a significant reduction in the CRP, WBC, α1, and α2 globulins from T0 to T2 (p = 0.046, p = 0.002, p = 0.008, and p = 0.002, respectively). Participants showed a significant decrease in steroid administration during the observation period. A significant reduction in the HBI of CD patients at all three timepoints and a similarly significant decrease in the pMS of UC patients from baseline to T1 were recorded. Statistically significant changes were observed in all questionnaires during follow-up as well as an overall improvement in the HRQoL. The interdependence analysis carried out between the biomarkers and the scores of the individual subscales showed a significant correlation between the variation (Δ) of the CRP, Hb, MCH, and MCV with physical and emotional dimensions of the SF-36 and FACIT-F tools; work productivity loss expressed by some of the WPAI:GH items negatively correlated with the ΔWBC and positively with the ΔMCV, ΔMCH, and Δ α1 globulins. A sub-analysis according to the type of treatment showed that patients receiving infliximab experienced a more pronounced improvement in their HRQoL (according to both SF-36 and FACIT-F) compared with patients receiving vedolizumab. CONCLUSIONS: Both infliximab and vedolizumab played an important role in contributing to the improvement of the HRQoL in IBD patients by also reducing inflammation and, consequently, steroid use in patients with an active disease. HRQoL, being one of the treatment goals, should also be assessed when taking charge of IBD patients to assess their clinical response and remission. The specific correlation between the biomarkers of inflammation and life's spheres, as well as their possible role as clinical markers of HRQoL, should be further investigated.