Cost-effectiveness of Adalimumab and Surgery vs Adalimumab in HS (HS-COST)

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

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.

Study Overview

• Status: Unknown
• Conditions: Hidradenitis Suppurativa
• Intervention / Treatment: Drug: Adalimumab Injection; Procedure: Wide Excision

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 128
• Phase: Phase 4

Contacts and Locations

Study Locations

• Netherlands
  • Rotterdam, Netherlands
    • Recruiting
    • Erasmus MC
    • Contact: Kelsey van Straalen, MD; Phone Number: + 31 107040110; Email: k.vanstraalen@erasmusmc.nl
    • Principal Investigator: Martijn van Doorn, MD, PhD
    • Sub-Investigator: Errol Prens, MD, PhD
    • Sub-Investigator: Hessel van der Zee, MD, PhD
    • Sub-Investigator: Allard Vossen, MD
    • Sub-Investigator: Kelsey van Straalen, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Adalimumab Monotherapy; 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; 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.; Other Names: Humira
Experimental: Adalimumab + Surgery; 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.	Drug: Adalimumab Injection; 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.; Other Names: Humira; Procedure: Wide Excision; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Erasmus Medical Center
• Collaborators: Prothya Biosolutions
• Investigators: Principal Investigator: Martijn van Doorn, MD, PhD, Erasmus Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): July 31, 2018
• Primary Completion (Anticipated): July 31, 2022
• Study Completion (Anticipated): July 31, 2022

Study Registration Dates

• First Submitted: July 4, 2017
• First Submitted That Met QC Criteria: July 17, 2017
• First Posted (Actual): July 18, 2017

Study Record Updates

• Last Update Posted (Actual): February 8, 2019
• Last Update Submitted That Met QC Criteria: February 7, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: Cost-effectiveness; Adalimumab; Acne inversa
• Additional Relevant MeSH Terms: Sweat Gland Diseases; Skin Diseases; Infections; Bacterial Infections; Bacterial Infections and Mycoses; Skin Diseases, Infectious; Suppuration; Skin Diseases, Bacterial; Hidradenitis Suppurativa; Hidradenitis; Anti-Inflammatory Agents; Antirheumatic Agents; Adalimumab
• Other Study ID Numbers: HS-COST

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No