SKIN Disease Profiling by an Exploratory, pRospective, Biomarker Study in dermatoloGY Practice (SKINERGY)

Leiden University Medical Center (LUMC)

Status: Enrolling

Conditions: Chronic Spontaneous Urticaria (CSU); Atopic Dermatitis (AD); Hidradenitis Suppurativa (HS); Psoriasis (PsO); CTCL/ Mycosis Fungoides

Study type: Observational

Funder types: Other

Identifiers

NCT07021495

NGID (Other Grant/Funding Number)

NWA.1389.20.182 (Other Grant/Funding Number)

SKINERGY

Details and patient eligibility

About

The goal of this observational study is to comprehensively profile six immune-mediated inflammatory diseases, including atopic dermatitis (AD), plaque psoriasis (PSO), hidradenitis suppurativa (HS), cutaneous T-cell lymphoma subtype mycosis fungoides (MF), chronic spontaneous urticaria (CSU), and cutaneous lupus erythematosus (CLE) in daily practice. Data will be compared with data from healthy volunteers. This study is part of the larger NGID (Next Generation ImmunoDermatology) initiative, of which the main objective is to develop infrastructure that enables personalised patient care. The main questions the SKINERGY study aims to answer are:

• Which biomarkers can discriminate between responders and non-responders to treatment in patients with AD, CLE, CSU, HS, MF, and PSO?
• How do disease-related biomarkers in patients with AD, CLE, CSU, HS, MF, and PSO differ from those in healthy volunteers?
• Which (multi-omics) biomarkers are associated with disease subtypes and predict response or non-response to (targeted) therapies in daily clinical practice?
• How do biomarker profiles compare across different cohorts of patients with immune-mediated inflammatory skin diseases (AD, CLE, CSU, HS, MF, PSO)
• How do biomarker levels change over time in response to treatment in these patient populations?
• Which skin tissue biomarkers are associated with disease progression or treatment response?
• How do the genomic profiles of patients differ across diseases or correlate with treatment outcomes?
• Can additional imaging biomarkers enhance the characterization of disease profiles or treatment monitoring over time?

Researchers will compare both differences beween patients within a disease group in different treatment arms, as well as patients within the same treatment arm. Additionally, biomarker profiles of patients with different diseases will be evaluated. These comparisons will be made to see if shared or distinct biomarker patterns exist across diseases and treatments, which could inform patient stratification, optimize therapeutic decision-making, and identify potential targets for future interventions.

Participants will start medication according to national guidelines for the treatment of their inflammatory skin disease (AD: Cyclosporin A, anti-IL4/13, or anti-JAK; PSO: anti-TNF, anti-IL23, ani-IL17, anti-TYK2; HS: anti-TNF, anti-IL17; MF: CHLORM, TSC, PUVA-UV-B; CSU: anti-IgE, Cyclosporin A, anti-BTK*; CLE: TSC, HCQ, MTX)

*once approved and reimbursed in the Netherlands

Participants will:

• Take the prescribed medication for their skin disease (in line with standard care in the Netherlands).
• Visit the clinic for a study visit combined with their standard care appointment 3 times (baseline, month 3, and month 6. An additional 4th visit at month 12 is optional).
• Fill in an online set of questionnaires from home, 3 times during the study period (an additional 4th time is optional).
• Patients with CSU fill in the UAS7 (and if applicable the AAS7) daily for the study period.

Full description

Atopic dermatitis (AD), cutaneous lupus erythematosus (CLE), chronic spontaneous urticaria (CSU), hidradenitis suppurativa (HS), cutaneous T-cell lymphoma (CTCL, subtype mycosis fungoides, MF), and plaque psoriasis (PSO) are diverse immune-mediated inflammatory skin diseases with complex and often poorly understood pathophysiologies. Genetic, immunological, and environmental factors contribute variably across these conditions, leading to heterogeneous clinical presentations. Despite advances, the identification and validation of specific biomarkers remain limited, hampering precise diagnosis, disease subtyping, and treatment response prediction. For example, AD involves epidermal barrier defects and immune dysregulation; CLE features autoimmune mechanisms and diverse clinical subtypes; CSU results from mast cell activation; HS is driven by follicular occlusion and chronic inflammation; CTCL involves malignant T-cell proliferation in the skin; and PSO is characterized by immune-driven keratinocyte hyperproliferation. The Next Generation ImmunoDermatology project aims to address these challenges by deeply profiling these diseases to discover biomarkers that define disease endotypes and predict therapy response, ultimately enabling personalized treatment strategies.

The investigations will profile various aspects of the disease, including patient-reported outcomes, the clinician-reported outcomes, biophysical, imaging, cellular, microbiological, molecular, blood-based and tissue biomarkers.

This multicenter, open-label, longitudinal biomarker study follows 720 patients with six inflammatory skin diseases-AD, PSO, HS, CSU, CLE, and MF-for one year after starting standard-of-care treatment. Multimodal data are collected at baseline, 3, 6, and 12 months. An additional 120 healthy controls are included for baseline comparison and followed for 6 weeks. Each disease includes multiple treatment arms (N=40 per arm):

• AD: cyclosporine A; anti-IL-4/13 (dupilumab, tralokinumab, lebrikizumab); JAK1 inhibitors (upadacitinib, abrocitinib)
• PSO: anti-IL-23 (guselkumab, risankizumab, tildrakizumab); anti-IL-17 (secukinumab, ixekizumab, brodalumab, bimekizumab); anti-TNFα (adalimumab, certolizumab); TYK2 inhibitor (deucravacitinib)
• HS: anti-TNFα (adalimumab); anti-IL-17 (secukinumab, bimekizumab*)
• MF: topical chlormethine; topical corticosteroids; phototherapy (PUVA/UV-B)
• CSU: anti-IgE (omalizumab*); cyclosporine A; BTK inhibitors* (remibrutinib, rilzabrutinib)
• CLE: topical corticosteroids; hydroxychloroquine; methotrexate

Enrollment: 840 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

Patients:

1. Able to understand and provide a written informed consent prior to any study procedures
2. Male or non-pregnant female, ≥18 years of age
3. Patient is willing to refrain from extensively washing (including bathing, swimming) the target lesional skin 12 hours before every study visit day.
4. Patient is willing and able to comply with the study protocol
5. Female participants are willing to not get pregnant between M0 until M12, from study entry to the last study visit
6. The patient is willing to start the prescribed treatment.

Disease-specific inclusion criteria

For patients with AD:

To be eligible to participate in this study, a subject must meet all of the following criteria:

6. Diagnosis and history of chronic, moderate-to-severe AD (by the Eichenfield revised criteria of Hanifin and Rajka for at least 3 years before baseline visit.

7. Documented recent history (last 6 months) of eligibility for (local or systemic) treatment with immunosuppressants, biologics or JAK-inhibitors.

8. When applicable, documented recent history (last 6 months) of inadequate response to treatment with topical therapy, immunosuppressants, biologics or JAK-inhibitors.

9. Current treatment can include moisturizers, topical treatment and/or systemic treatments with preferable wash-out (see exclusion criterion #9). On-study treatment is at physician and patient discretion but must include eligibility to starting new systemic treatment.

10. EASI≥7 (moderate-to-severe disease) 11. At least one suitable target lesion at the discretion of the investigator 12. Intention to start treatment with cyclosporine A, dupilumab, tralokinumab, lebrikizumab or a JAK1-inhibitor (abrocitinib or upadacitinib)

For patients with CLE:

Participants must have a diagnosis of CLE, including SCLE, CDLE or LET that fulfil the following:

6. Confirmed CLE diagnosis by clinicopathological correlation. 7. An overall CLE Disease Area and Severity Index Activity (CLASI-A) Score ≥3 without counting any diffuse alopecia or oral ulcers.

7. Intention to start treatment with TCS, hydroxychloroquine or methotrexate (combination or mono-treatment).

If participating in the exploratory study with the skin biopsy: location of the lesion(s) selected for biopsy preferably outside the facial area (possible are e.g., neck, chest, back, limbs, scalp, ear etc.).

For patients with CSU:

6. Diagnosis of CSU (moderate to severe according to international guidelines (Zuberbier et al, 2022)) for ≥3 months and symptomatic disease despite treatment with second generation H1 antihistamines (up to fourfold the approved dose).

7.Patients currently on an antihistamine (up to fourfold the approved dose) must be on a stable dose for at least 2 weeks prior to day 1 and must maintain the same stable dose throughout the treatment period.

8. Intention to start (add-on to antihistamine) treatment of omalizumab, cyclosporine A or BTK inhibitor*. (*when approved and reimbursed in NL)

For patients with HS:

6. Patient with a history of signs and symptoms consistent with moderate-to-severe HS, based on IHS4 score (Zouboulis et al., 2017), for at least 1 year prior to baseline 7. Current treatment can include topical treatment. On-study treatment is at physician and patient discretion but must include eligibility to starting systemic treatment 8. Intention to start treatment with anti-TNF or anti-IL17 (secukinumab, bimekizumab*) *when approved and reimbursed in NL.

For patients with MF:

6. A confirmed diagnosis of CTCL MF type and stage classification via histology or clinicopathological correlation 7. For the stage IA-IIA CTCL patients: at least one patch and/or one plaque lesion is present 8. Intention to start treatment with topical chlormethine, topical corticosteroids or phototherapy (PUVA / UV-B).

For patients with PSO:

6. Diagnosed with chronic plaque psoriasis at least 6 months prior to study participation 7. PASI≥5 with at least one suitable target lesion at the discretion of the investigator 8. Current treatment can include moisturizers, topical treatment and/or systemic treatments with preferable wash-out. On-study treatment is at physician and patient discretion but must include eligibility to starting new systemic treatment 9. Intention to start treatment with biologics: anti-TNF, anti-IL23, anti-IL17 or anti-TYK2

Healthy volunteers:

All healthy volunteers must meet all of the following inclusion criteria:

1. Signed informed consent before any study-mandated procedure.
2. Male or non-pregnant female volunteers, ≥18 years of age
3. Subject is in stable good health as per judgement of the investigator based upon the results of medical history and assessments performed at baseline.
4. No clinically significant skin disease as judged by the investigator.
5. No history of hypertrophic scarring or keloid.
6. Subject is willing to refrain from extensively washing (including bathing, swimming) the skin 12 hours before every study visit.
7. Subject is willing and able to wash out and withhold any topical treatment (prescription and over-the-counter products) in the investigational area for 2 weeks prior to Day 1.
8. Subject is willing to refrain from application of any topical product (e.g. ointments, cream, or washing lotions) on the skin 24 hours prior to every study visit day.
9. Subject is willing and able to wash out any antibiotic therapy for 14 days prior to Day 1.
10. Subject is willing and able to comply with the study protocol.
11. Female participants are willing to not get pregnant from study entry to the last study visit

Exclusion criteria

Patients:

1. Have any other relevant skin infection/disease in the treatment area other than the investigated skin disease.

2. Subjects who have received treatment with any non-marketed drug substance (that is, an agent which has not yet been made available for clinical use following registration) within 4 weeks prior to the baseline visit.

3. Any other condition, disease, or known factor that could interfere with the study conduct or the study objectives as per judgement of the investigator. 4. Having received treatments for the investigated skin disease within the following intervals prior to the start of the study is not a strict exclusion criterion since this is a real-world study. However, preferred intervals for washout are as follows:

   • 1 week for topical treatment, e.g. corticosteroids, retinoids, vitamin D analogs, calcineurin inhibitors
   • 4 weeks for phototherapy, e.g. UVB, PUVA, PDT
   • 4 weeks for non-biologic systemic treatment, e.g. retinoids, methotrexate, cyclosporine, JAK inhibitors
   • 8 weeks for radiotherapy or surgery in the treatment area
   • 8 weeks for biologics
   • 3 months for any systemic chemotherapeutical treatment

Disease specific exclusion criteria for patients with CLE:

5. Diagnosed with SLE

Disease specific exclusion criteria for patients with CSU:

5. Treatment with omalizumab within 8 weeks prior to Day 1 6. Urticarial or angioedema symptoms such as urticarial vasculitis, erythema multiforme, cutaneous mastocytosis (urticaria pigmentosa) and hereditary, acquired angioedema or drug-induced (e.g., due to C1 esterase inhibitor deficiency, ACE-inhibitor induced).

Disease specific exclusion criteria for patients with MF:

5. Ongoing uncontrolled active skin infection, other than secondary impetiginized CTCL lesions as judged by the investigator

Disease specific exclusion criteria for patients with PSO:

5. Having primarily erythrodermic, pustular or guttate psoriasis; 6. Having drug-induced psoriasis;

Healthy volunteers:

All healthy volunteers must meet none of the following exclusion criteria:

1. History of immunological abnormality (e.g. immune suppression, severe allergy, or anaphylaxis) that may interfere with study objectives as per judgement of the investigator.

2. History or symptoms of any uncontrolled, significant disease including (but not limited to), a neurological, psychiatric, endocrine, cardiovascular, respiratory, gastrointestinal, hepatic, or renal disorder that may interfere with the study objectives as per judgement of the investigator.

3. The use of systemic antibiotic therapy for >2 months in the past 12 months.

4. The use of any immunosuppressive or immunomodulatory therapy within the past 30 days prior to Day 1.

5. Loss or donation of blood over 500mL within three months prior to baseline. Participation in an investigational drug study within 3 months prior to baseline visit or more than 4 times a year.

6. History of alcohol consumption exceeding 5 standard drinks per day on average within 3 months prior to baseline. Alcohol consumption will be prohibited for at least 24 hours preceding each study visit.

7. Positive urine test for drugs or history of abuse at baseline. 9. Exposure to high doses of UV radiation is not permitted within 3 weeks of the first study visit until the end of the study 10. Extreme physical activities are not permitted within 48 hours before each study visit 11. Any other condition, disease, or known factor that could interfere with the study conduct or the study objectives as per judgement of the investigator.

Trial design

840 participants in 18 patient groups

AD - CsA

Description:

Adult patients with moderate-to-severe AD who start treatment with cyclosporine A. Cyclosporine A (CsA) is a lipophilic, cyclic undecapeptide produced by fungi, acting as a potent immunosuppressant by inhibiting T-cell receptor activation. It's prescribed twice daily at 3-5 mg/kg/day, starting with 3 mg/kg/day and increasing based on clinical response. CsA inhibits cytokine production, especially interleukin-2 (IL-2). In the Netherlands, CsA is the only oral immunosuppressant for moderate-to-severe atopic dermatitis (AD). CsA has shown superiority over placebo in numerous trials, and is the treatment of choice for severe AD. Common adverse reactions include renal dysfunction, tremor, hirsutism, hypertension, diarrhea, nausea, and vomiting. Contraindications include hypersensitivity and certain drug combinations. Regular monitoring is necessary due to potential risks like acute infections, hepatotoxicity, and renal toxicity.

AD - Anti-IL4/13

Description:

Adult patients with AD who start treatment with anti-IL4/13 (dupilumab, tralokinumab, lebrikizumab). Dupilumab is a human monoclonal antibody that targets the IL-4 receptor alpha chain, inhibiting IL-4 and IL-13. In the Netherlands, it's the first biologic registered for moderate-to-severe atopic dermatitis (AD). Administered subcutaneously every other week at 300mg, following a loading dose of 600mg at baseline, it follows standard treatment guidelines with regular monitoring. Dupilumab's efficacy has been shown in clinical trials, with long-term benefits in AD. Common adverse reactions include injection site reactions, conjunctivitis, arthralgia, oral herpes, and eosinophilia. Tralokinumab, another monoclonal antibody, neutralizes IL-13 to reduce AD symptoms. Administered similarly to dupilumab, its efficacy has also been demonstrated in trials, showing superiority over placebo. Common ADRs include upper respiratory infections, injection site reactions, and conjunctivitis.

AD - JAK1 inhibitor

Description:

Adult patients with AD who start treatment with JAK1 inhibitors (upadacitinib/abrocitinib). Upadacitinib and abrocitinib are selective JAK1 inhibitors that reduce immune system activity by blocking Janus Kinases, enzymes involved in inflammatory responses, which drive atopic dermatitis (AD) symptoms like eczematous skin lesions and pruritus. Upadacitinib is dosed at 15mg or 30mg once daily, with clinical trials showing significant improvements in IGA-AD, EASI 75, and pruritus compared to placebo. Common ADRs include upper respiratory infections, acne, and herpes simplex. Abrocitinib is dosed at 100mg or 200mg once daily, with 200mg recommended for severe AD. It has also shown significant efficacy in clinical trials. ADRs for abrocitinib include nausea, headache, and acne.

PSO - Anti-TNF

Description:

Adult patients with moderate-to-severe PSO who start treatment with anti-TNF (e.g. adalimumab, certolizumab, biosimilars). Adalimumab is a monoclonal antibody used to treat moderate-to-severe rheumatoid arthritis, plaque psoriasis, and hidradenitis suppurativa. It inhibits TNF, reducing inflammation. Common adverse events include infections, injection site reactions, headache, and musculoskeletal pain. For plaque psoriasis, the recommended dose is 80 mg at week 0, followed by 40 mg biweekly. Certolizumab, another TNF inhibitor, treats plaque psoriasis with an initial dose of 400 mg at weeks 0, 2, and 4, followed by 200 mg biweekly (or 400 mg if efficacy is insufficient).

PSO - anti-IL23

Description:

Adult patients with moderate-to-severe PSO who start treatment with anti-IL 23 (e.g. guselkumab, risankizumab, tildrakizumab). Guselkumab (Tremfya) is an anti-IL-23 monoclonal antibody approved for moderate-to-severe plaque psoriasis in patients eligible for systemic treatment. It blocks IL-23 interaction with its receptor, reducing pro-inflammatory cytokines. The recommended dose is 100 mg at weeks 0 and 4, followed by 100 mg every 8 weeks. Common adverse reactions include respiratory tract infections and diarrhea. Risankizumab (Skyrizi) also targets IL-23, with a dosing regimen of 150 mg at weeks 0 and 4, followed by 150 mg every 12 weeks. Common AEs include respiratory infections, injection site reactions, tinea, headache, itching, fatigue, and rash. Tildrakizumab (Ilumetri) targets the IL-23 p19 subunit. It is dosed at 100 mg at weeks 0 and 4, followed by 100 mg every 12 weeks. Common AEs include respiratory infections, injection site pain, nausea, diarrhea, and headache.

PSO - anti-IL17

Description:

Adult patients with moderate-to-severe PSO who start treatment with anti IL-17 (e.g. secukinumab, ixekizumab, brodalumab, bimekizumab). Secukinumab is an IL-17A inhibitor for psoriasis and hidradenitis suppurativa. It blocks IL-17 interaction with its receptor. The dose is 300 mg at weeks 0, 1, 2, 3, and 4, followed by 300 mg monthly. Common AEs include respiratory infections, nasopharyngitis, oral herpes, diarrhea, headache, and fatigue. Ixekizumab, another IL-17A inhibitor, is dosed at 160 mg in week 0, followed by 80 mg every 2 weeks for 10 weeks, then 80 mg every 4 weeks. AEs include injection site reactions and respiratory infections. Brodalumab binds IL-17RA, with a dose of 210 mg at weeks 0, 1, and 2, followed by biweekly doses. Common AEs include infections, tinea, headache, and fatigue. Bimekizumab inhibits IL-17A, IL-17F, and IL-17A/F, dosed at 320 mg at weeks 0, 4, 8, 12, and 16, followed by 320 mg every 8 weeks. Common AEs include infections, candidiasis, and fatigue.

PSO - anti-TYK2

Description:

Adult patients with moderate-to-severe PSO who start treatment with TYK2 inhibitor (e.g. deucravacitinib). Deucravacitinib is a selective TYK2 inhibitor used for moderate-to-severe plaque psoriasis. It selectively binds the allosteric pocket of TYK2, leading to high selectivity in inhibition. Inhibiting TYK2 interferes with cytokine signaling involved in plaque psoriasis. The recommended dose is 6 mg daily. The most common adverse reactions occurring in ≥1% of patients are (viral) upper respiratory infections, nasopharyngitis, pharyngitis, sinusitis, herpes simplex, oral ulceration, acneiform rash, folliculitis, and increased creatine kinase levels.

HS - anti-TNF

Description:

Adult patients with moderate-to-severe HS who start treatment with anti-TNF (e.g. adalimumab, certolizumab, biosimilars). Adalimumab is a monoclonal antibody used to treat moderate-to-severe rheumatoid arthritis, plaque psoriasis, and hidradenitis suppurativa. It inhibits TNF, reducing inflammation. Common adverse events include infections, injection site reactions, headache, and musculoskeletal pain. For hidradenitis suppurativa, the dose starts with 160 mg at week 0, then 80 mg at week 2, followed by 40 mg weekly or 80 mg biweekly.

HS - anti-IL17

Description:

Adult patients with moderate-to-severe HS who start treatment with anti-IL 17, i.e. secukinumab, bimekizumab\* (\*once approved and reimbursed in the Netherlands). Secukinumab is an IL-17A inhibitor for psoriasis and hidradenitis suppurativa. It blocks IL-17 interaction with its receptor. The dose is 300 mg at weeks 0, 1, 2, 3, and 4, followed by 300 mg monthly. Common AEs include respiratory infections, nasopharyngitis, oral herpes, diarrhea, headache, and fatigue. Ixekizumab, another IL-17A inhibitor, is dosed at 160 mg in week 0, followed by 80 mg every 2 weeks for 10 weeks, then 80 mg every 4 weeks. AEs include injection site reactions and respiratory infections. Brodalumab binds IL-17RA, with a dose of 210 mg at weeks 0, 1, and 2, followed by biweekly doses. Common AEs include infections, tinea, headache, and fatigue. Bimekizumab inhibits IL-17A, IL-17F, and IL-17A/F, dosed at 320 mg at weeks 0, 4, 8, 12, and 16, followed by 320 mg every 8 weeks. Common AEs include infections, cand

MF - Topical chlormethine

Description:

Adult patients with stage 1 or 2 cutaneous T-cell lymphoma subtype mycosis fungoides who start treatment with topical chlormethine. Chlormethine (CL) gel 0.016% (Ledaga®) is an FDA-approved orphan drug (since August 23, 2013) for stage IA and IB mycosis fungoides in patients previously treated with skin-directed therapy. It forms DNA interstrand crosslinks, blocking replication and transcription, leading to cell death in rapidly dividing cells. CL gel showed no systemic absorption up to 6 hours post-application and after 1 month (Lessin et al., 2013). In a follow-up study with CL gel 0.04%, no detectable drug or degradation product was found in blood up to 6 months (Kim et al., 2014). In a randomized trial (n=128, median 52 weeks), 61.7% had skin-related side effects, mainly dermatitis (54.7%), pruritus (20.3%), infections (11.7%), ulceration/blistering (6.3%), and hyperpigmentation (5.5%). Hypersensitivity occurred in 2.3%. No systemic side effects or overdoses were reported.

MF - Topical corticosteroids

Description:

Adult patients with stage 1 or 2 cutaneous T-cell lymphoma subtype mycosis fungoides who start treatment with topical corticosteroids. Topical corticosteroids are anti-inflammatory medications that are used in the treatment of various inflammatory skin diseases, such as cutaneous T-cell lymphoma subtype mycosis fungoides. Corticosteroids inhibit the release of inflammation factors and therefore, the inflammatory response is reduced. Topical corticosteroids are divided in four subclasses, based on their potency. Topical corticosteroids are generally described as highly effective in the treatment of certain skin diseases. The recommended dose of topical corticosteroids depends on the subclass and specific therapy, however, generally 2 applications per day are recommended over a limited time period. AE's as skin thinning, and increased risk of infections are often reported.

MF - PUVA/UB-B

Description:

Adult patients with stage 1 or 2 cutaneous T-cell lymphoma subtype mycosis fungoides who start treatment with PUVA/UV-B. Psoralen UV-A (PUVA) is used to treat cutaneous T-cell lymphoma subtype mycosis fungoides. It combines UVA light with psoralen, a drug that makes the skin more sensitive to light. Typically, 2-3 treatments per week are required for effectiveness. Common side effects include nausea (due to psoralen) and skin redness (from UVA). Long-term use may lead to premature skin aging. UV-B light therapy, including narrowband UVB, is also used for (folliculotropic) mycosis fungoides. It uses short-wave UVB light that penetrates the outer skin layers. While generally safer than older phototherapies, long-term treatment may increase the risk of skin cancer.

CSU - anti-IgE

Description:

Adult patients with moderate to severe CSU who start (add-on) treatment with anti-IgE. Omalizumab is a highly effective treatment for chronic spontaneous urticaria. It is a recombinant humanized IgG1 monoclonal antibody targeting immunoglobulin E (IgE). Experimental models in cynomolgus monkeys and mice have been used to study its pharmacokinetics. The mouse model focused on antigen-independent behavior in the absence of IgE binding. After subcutaneous administration, bioavailability was 90% in mice and 64-104% in monkeys. Peak concentrations occurred around day 5, with a half-life of approximately 7 days. Clearance of omalizumab:IgE complexes was significantly slower than that of free IgE, leading to up to 20-fold increases in total IgE levels. In use since 2004, omalizumab has a well-established safety profile in asthma, CSU, and CRSwNP, both in trials and post-marketing. The most common AEs in CSU include nasopharyngitis, headache, sinusitis, and injection site reactions.

CSU - CsA

Description:

Adult patients with moderate to severe CSU who start (add-on) treatment with cyclosporin A. Cyclosporine A (CsA) is a lipophilic, cyclic undecapeptide produced by fungi, acting as a potent immunosuppressant by inhibiting T-cell receptor activation. It's prescribed twice daily at 3-5 mg/kg/day, starting with 3 mg/kg/day and increasing based on clinical response. CsA inhibits cytokine production, especially interleukin-2 (IL-2). In the Netherlands, CsA is the only oral immunosuppressant for moderate-to-severe atopic dermatitis (AD). CsA has shown superiority over placebo in numerous trials, and is the treatment of choice for severe AD. Common adverse reactions include renal dysfunction, tremor, hirsutism, hypertension, diarrhea, nausea, and vomiting. Contraindications include hypersensitivity and certain drug combinations. Regular monitoring is necessary due to potential risks like acute infections, hepatotoxicity, and renal toxicity.

CSU - anti-BTK

Description:

Adult patients with moderate to severe CSU who start (add-on) treatment with anti-BTK\*. Bruton's tyrosine kinase (BTK) inhibitors block BTK, a key enzyme in B-cell receptor signaling that controls B-cell activation and survival. By inhibiting BTK, these drugs disrupt B-cell function and pathological immune responses. They are mainly approved for B-cell cancers like chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). Common BTK inhibitors include ibrutinib, acalabrutinib, and zanubrutinib, which are orally administered and generally well tolerated. BTK also plays a crucial role in mast cell and basophil activation via the FcεRI receptor, central to chronic spontaneous urticaria (CSU). Inhibiting BTK blocks mast cell degranulation and histamine release, reducing symptoms in CSU patients, especially those unresponsive to antihistamines or omalizumab. This makes BTK inhibitors promising oral therapies for CSU. \*once approved and reimbursed in the Netherlands

CLE - Topical corticosteroids

Description:

Adult patients with mild to severe chronic lupus erythematosus (CLE) who start treatment with topical corticosteroids. Topical corticosteroids are anti-inflammatory medications that are used in the treatment of various inflammatory skin diseases, such as cutaneous T-cell lymphoma subtype mycosis fungoides. Corticosteroids inhibit the release of inflammation factors and therefore, the inflammatory response is reduced. Topical corticosteroids are divided in four subclasses, based on their potency. Topical corticosteroids are generally described as highly effective in the treatment of certain skin diseases. The recommended dose of topical corticosteroids depends on the subclass and specific therapy, however, generally 2 applications per day are recommended over a limited time period. AE's as skin thinning, and increased risk of infections are often reported.

CLE - Hydroxychloroquine

Description:

Adult patients with mild to severe chronic lupus erythematosus (CLE) who start treatment with HCQ. HCQ is an antimalarial used to treat rheumatoid arthritis, systemic lupus erythematosus, and cutaneous lupus. It accumulates in lysosomes, raising pH, and inhibits TLR3, TLR7, and TLR9, reducing plasmacytoid dendritic cell activation and lowering IFNα and TNF production. HCQ also suppresses T and B cell activation, reducing Th1, Th2, and Th17 responses, while sparing cytotoxic T cells. Orally, HCQ has 74% bioavailability, a Tmax of 2-4.5 hours, and a plasma half-life around 32 days. It concentrates in blood cells and tissues like lungs, kidneys, and eyes. Metabolized in the liver, it is cleared by the kidneys. Common side effects are nausea, abdominal pain, and diarrhea, often reduced by taking HCQ with food. Risks include hypoglycemia, retinopathy, cardiac toxicity, and blood count changes, requiring regular monitoring.

CLE - Methotrexate

Description:

Adult patients with mild to severe chronic lupus erythematosus (CLE) who start treatment with methotrexate. Methotrexate (MTX), introduced in 1947 for cancer, has been used since the 1980s at low doses to treat rheumatoid arthritis (RA). It is given once weekly, orally or by injection (s.c., i.m., i.v.). MTX's anti-inflammatory effects involve inhibition of nucleotide synthesis, NF-κB signaling, JAK-STAT pathway modulation, nitric oxide production, adenosine release, and regulation of certain RNAs. Orally, MTX has \~70% bioavailability with peak levels in 1-2 hours; subcutaneous administration offers higher and faster plasma levels. About 50% binds serum proteins and accumulates in liver, kidneys, and spleen as polyglutamates. The half-life varies from 3 to 17 hours. Common side effects include nausea, fatigue, mouth sores, liver enzyme elevation, and leukopenia. Early detection allows reversibility; patients are closely monitored. Folic acid is recommended to reduce adverse events.