Table 4 List of pre specified objectives

Primary

Objective A:

Primary efficacy endpoint:

To evaluate the effect of biosimilar infliximab on disease specific disability in patients with chronic low back pain and Modic changes type 1

Oswestry Disability Index change from baseline to day 154 (5 months)

Secondary

Objective B:

Secondary endpoints:

To evaluate the effect of biosimilar infliximab on bone marrow oedema in patients with chronic low back pain and Modic changes type 1

– Short tau inversion recovery (STIR) signal (intensity and extent) of MCs from baseline to 5/6 months

Objective C:

Secondary endpoints:

To evaluate the effect of biosimilar infliximab on pain in patients with chronic low back pain and Modic changes type 1

– LBP intensity at day 154 (5 months) follow-up

Objective D:

Secondary endpoints:

To evaluate the effect of biosimilar infliximab on disease specific disability in patients with chronic low back pain and Modic changes type 1

– Roland Morris Disability Questionnaire at day 154 (5 months) follow-up

Objective E:

Secondary endpoints:

To evaluate whether the short tau inversion recovery (STIR) signal (intensity and extent) of Modic changes type 1 on baseline MRI predicts clinical outcome

– ODI score at day 154 (5 months) follow-up

– LBP intensity at day 154 (5 months) follow-up

Objective F:

Secondary endpoints:

To evaluate the effect of biosimilar infliximab on health-related quality of life in patients with chronic low back pain and Modic changes type 1

– Health-related quality of life (the EQ-5D) at day 154 (5 months) follow-up

Objective G:

Secondary endpoints:

To evaluate cost-effectiveness of biosimilar infliximab in patients with chronic low back pain and Modic changes type 1

– ODI score at day 154 (5 months) follow-up

– Health-related quality of life (the EQ-5D) at day 154 (5 months) follow-up

– Co-interventions (pharm. and non-pharmacological)

– Days with sick-leave

Objective H:

–

To evaluate the incidence of AEs and SAEs in patients who receive biosimilar infliximab

Exploratory

To evaluate the effect of biosimilar infliximab versus placebo on other outcome measures not mentioned above in patients with chronic low back pain and Modic changes type 1

Exploratory endpoints at day 154 (5 months) follow-up:

– Leg pain intensity

– Hours with LBP during the last 4 weeks

– Symptom-specific well-being

– Days with sick leave

– Co-interventions

– Patients’ satisfaction

– Global perceived effect

To evaluate the long-term effect of biosimilar infliximab versus placebo on pain and disability in patients with chronic low back pain and Modic changes type 1

Exploratory endpoints:

– ODI at 9 months follow-up

– Leg pain intensity at 9 months follow-up

To evaluate the feasibility of machine learning to assess imaging features of Modic changes type 1

Exploratory endpoints:

– Machine detected features of MCs baseline and 6 months

To investigate the underlying biological mechanisms of Modic changes type 1 through combined gene expression and epigenetic profiling and correlate with clinical outcome

Exploratory endpoints:

– Epigenetic patterns, longitudinal gene- and protein expression, genetic variation at baseline, end of treatment and at 5 months

To identify biomarkers for any TNF-alfa blockers response in patients with chronic low back pain and Modic changes type 1

Exploratory endpoints:

– Protein expression at baseline