Cost-effectiveness of Adalimumab and Surgery vs Adalimumab in HS

Study Overview
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Brief Summary
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The primary objective of this randomized controlled clinical trial in a real life setting is to evaluate the cost-utility of limumab monotherapy compared with the combination of adalimumab and a maximum of three surgeries after two years of treatment in adult patients with moderate to severe HS.

Detailed Description
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The primary objective of this randomized controlled clinical trial in a real life setting is to evaluate the cost-utility of limumab monotherapy (Group A) with the combination of adalimumab and a maximum of three surgeries (Group B) years of treatment in adult patients with moderate to severe HS. Patients in group A will be treated with adalimumab monotherapy according to normal clinical practice and will be given the possibility to crossover into Group B when they do not achieve the HiSCR after 6 months of treatment. Additionally patients will be offered treatment with infliximab, according to clinical practice, until the last surgery. Patients in group B will receive adalimumab combined with a maximum of three adjuvant excisions of active lesions, both according to routine clinical practice.

Official Title
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Cost-effectiveness of Adalimumab With Adjuvant Surgery Versus Adalimumab Monotherapy in the Treatment of Hidradenitis Suppurativa'

Conditions
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Hidradenitis Suppurativa

Intervention / Treatment
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* Procedure: Wide Excision
* Drug: Adalimumab Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years. Moderate to (very) severe HS defined as a score of ≥3 points on the PGA (range 1-5) and with a DLQI of at least 11 (range 0-30). Indication for adalimumab: i.e. uncontrolled disease (HS) under conventional therapy and/or minor surgery. A diagnosis of HS for more than six months prior to baseline. Clearance of HS can reasonably be achieved with three surgical interventions as based on consensus between two dermatosurgeons. Willing and able to undergo general anaesthesia or procedural sedation and analgesia. Able and willing to give written informed consent and to comply with the study requirements. Exclusion Criteria: Contraindication for treatment with adalimumab (sepsis or risk of sepsis, active or latent tuberculosis, serious active local and/or chronic infections, heart failure NYHA class III/IV, severe liver disease, pre-existing HIV, active viral hepatitis, demyelinating disease, or allergy to adalimumab or any other ingredients of HUMIRA®). Previous or current use of adalimumab or other anti-TNF-α therapy. Current or recurrent clinically significant skin condition in the HS treatment area other than HS. Presence of other uncontrolled clinically significant major disease. Pregnant and lactating women. Malignancy (except basal cell carcinoma), lymphoproliferative disease or a history of malignancy. Current use of oral antibiotics (a washout period of 14 days is required). Current use of oral corticosteroids (a washout period of 30 days is required).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients will be treated with either the combination of adalimumab and surgery or adalimumab monotherapy for two years, both according to normal clinical practice. Patients on adalimumab monotherapy will be given the possibility to crossover into Group B when they do not achieve the HiSCR after 6 months of treatment. Additionally patients will be offered treatment with infliximab, according to clinical practice, until he last surgery.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Adalimumab Monotherapy<br>Adalimumab injections will be administered through subcutaneously in a weekly dose of 40mg from week 4 up to 24 months (V8), after an initial dose of 160mg at week 0 and a 80mg dose at week 2, continued for 2 years in total. | Drug: Adalimumab Injection<br>* Adalimumab will be administered through subcutaneous injections in weekly dose of 40mg from week 4 up to 24 months (V8), after an initial dose of 160mg at week 0 and a 80mg dose at week 2 until end of study or last surgery.<br>* Other names: Humira;|
| Experimental: Adalimumab + Surgery<br>Patients will be treated with a combination of adalimumab and wide excision, with a maximum of three surgical interventions within the first year. Adalimumab will be administered through subcutaneous injections in weekly dose of 40mg from week 4 up to 24 months (V8), after an initial dose of 160mg at week 0 and a 80mg dose at week 2, continued until the last surgery. | Procedure: Wide Excision<br>* Wide excision is performed under general anaesthesia or procedural sedation and analgesia (PSA). All lesional tissue, including fibrosis, is electrosurgically removed until the area is clear. The subcutaneous fat and epithelised sinus floors are left intact where possible. The wounds are left open to heal by secondary intention.<br>Drug: Adalimumab Injection<br>* Adalimumab will be administered through subcutaneous injections in weekly dose of 40mg from week 4 up to 24 months (V8), after an initial dose of 160mg at week 0 and a 80mg dose at week 2 until end of study or last surgery.<br>* Other names: Humira;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cost-utility | Cost-utility: costs / point change in QALY | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical efficacy using HiSCR | Assessment of clinical efficacy using HiSCR | 2 years | 
| Clinical efficacy using change in HS-PGA | Assessment of clinical efficacy using change in HS-PGA | 2 years | 
| Clinical efficacy using the number of flares | Assessment of clinical efficacy using the overall number of flares | 2 years | 
| Incidence and severity of treatment related adverse events | Assessment of tolerability and safety by recording the incidence and severity of all treatment related adverse events. | 2 years | 
| Cost-effectiveness | Cost-effectiveness: costs / point change in DLQI. | 2 years | 
| Quality of life using change in EQ-5D-5L | Assessment of changes in quality of life using the EuroQol-5D-5L (EQ-5D-5L) | 2 years | 
| Quality of life using change in DLQI | Assessment of changes in quality of life using the DLQI. | 2 years | 
| Quality of life using change in Skindex-17 | Assessment of changes in quality of life using the Skindex-17 | 2 years | 
| Treatment satisfaction | Assessment of treatment satisfaction on a 5 point Likert scale | 2 years | 
| High sensitivity CRP | Assessment of change in high sensitivity CRP. | 2 years | 
| Cytokines | Assessment of cytokines as possible predictive biomarkers in skin biopsies. | 3 months | 
| Change in parameters of metabolic syndrome | Assessment of the change in parameters of metabolic syndrome: waist circumference, blood pressure, fasting plasma glucose, triglycerides, and HDL levels. | 2 years | 
| Change in parameters of pre-diabetes | Assessment of the change in parameters of pre-diabetes using a HOMA model | 2 years | 
| Identification of blood metabolite profiles | Identification of metabolites or metabolite profiles related to HS phenotypes, disease severity. | 3 months | 
| Identification of metabolites associated with treatment response | Identification of metabolites (or metabolite profiles) predicting clinical response to treatment. | 3 months | 
| Assessment of changes in metabolite (profiles) | Assessment of changes in metabolites (or metabolite profiles) in response to treatment. | 3 months | 
| Relation between adalimumab trough concentrations and treatment response | Relation between adalimumab trough concentrations and treatment response | 3 months | 
| Relation between adalimumab trough concentrations in serum and skin samples | Relation between adalimumab trough concentrations in serum and adalimumab trough concentrations in skin biopsies. | 3 months | 
| Influence of patient characteristics on adalimumab serum trough concentrations | adalimumab trough concentrations | 3 months | 
| Predictive value of early dry-blood-spots | Predictive value of early adalimumab concentrations using dry-blood-spots on treatment response at 3 months | 3 months | 
| Objectively assessed therapy adherence using adalimumab trough concentrations | Objectively assessed therapy adherence using adalimumab trough concentrations | 2 years | 
| Objectively assessed therapy adherence using collected syringes | Objectively assessed therapy adherence using collected syringes | 2 years | 
| Patient reported therapy adherence using a diary | Patient reported therapy adherence using a diary recording date of every injection. | 2 years | 
| Impact of surgery on quality of life measured with DLQI | Assessment of the impact of wide excision on quality of life measured with DLQI | 8 weeks after each surgery | 
| Impact of surgery on work productivity measured with WPAI | Assessment of the impact of wide excision on work productivity and activity, measured with WPAI. | 8 weeks after each surgery | 
| Wound closure time | Assessment of time to complete healing after wide excision using patient reported closure time. | through study completion, an average of 15 months | 
| Recurrence rate | Assessment of the recurrence of HS lesions after wide excision | through study completion, an average of 15 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acne inversa, Adalimumab, Cost-effectiveness