Table 2. Table of Tissue response RCT objectives and outcome measures.

	Objectives	Outcome measures
Primary Objective	1. To establish an effective dose of adalimumab for downregulating the myofibroblast phenotype	1. Expression of mRNA for α-SMA.
Secondary Objectives	2. To determine the effectiveness of adalimumab for myofibroblast inhibition.	2.1. Expression of mRNA for COL-1A1, COL-3A1 and cadherin 11. 2.2. Levels of α-SMA protein. 2.3. Hardness of selected nodule. 2.4. Ultrasound imaging of nodule size. 2.5. Adverse event assessment comparing active and placebo groups using visual inspection of injection site, surgery site and laboratory reports.
Tertiary Objectives	3. Determine circulating levels of adalimumab and antibodies to adalimumab in the blood. 4. To assess if DD injection therapy would be acceptable to participants 5. To evaluate the health-related quality of life of participants	3. Analysis of blood sample. 4. Analysis of injection experience questionnaire 5. Analysis of EQ-5D-5L data to estimate utilities using quality-adjusted life years (QALYs).