Table 1

Key assessments in the PREDICTRA study

AssessmentTiming*Scoring/DetailsOther
Swollen joint count 66†Screening visit and all study visits (and all flare week visits, if applicable)Joint swelling will be classified as present (1), absent (0), replaced (9) or NASwollen joint count based on 28 joints will be used for the DAS28(ESR), DAS28(CRP), SDAI and CDAI calculations
Tender joint count 68†Screening visit and all study visits (and all flare week visits, if applicable)Joint pain/tenderness will be classified as present (1), absent (0), replaced (9) or NATender joint count based on 28 joints will be used for the DAS28(ESR), DAS28(CRP), SDAI and CDAI calculations
PGA of current disease activity (VAS)Screening visit and all study visits (and all flare week visits, if applicable)VAS consists of a 100 mm horizontal scale ranging from 0 (very low) to 100 (very high)The PhGA assessment will be used for the SDAI and CDAI calculation
PGA of disease activity (VAS) within 24 hoursScreening visit and all study visits (and all flare week visits, if applicable)VAS consists of a 100 mm horizontal scale ranging from 0 (very well) to 100 (very poorly)The PGA will be used for the DAS28(ESR), DAS28(CRP), SDAI and CDAI calculations
Patient assessment of pain (VAS) within past weekScreening visit and all study visits (and all flare week visits, if applicable)VAS consists of a 100 mm horizontal scale ranging from 0 (no pain) to 100 (severe pain)
Patient assessment of sleep disturbance (VAS) within past weekScreening visit and all study visits (and all flare week visits, if applicable)VAS consists of a 100 mm horizontal scale ranging from 0 (sleep is no problem) to 100 (sleep is a major problem)
Duration of morning stiffnessScreening visit and all study visits (and all flare week visits, if applicable)The average daily length during the past week in minutes (from time of awaking to time of maximal improvement)
Severity of morning stiffness in the past weekScreening visit and all study visits (and all flare week visits, if applicable)Rated on a numeric rating scale ranging from 0 (not severe) to 10 (very severe)
DAS28(ESR)Screening visit and all study visits (and all flare week visits, if applicable)Based on four variables‡: DAS28(ESR)=0.56× √(TJC28)+0.28× √(SJC28)+0.70×(ln)(ESR)+0.014×PGA
DAS28(CRP)Screening visit and all study visits (and all flare week visits, if applicable)Based on four variables§: DAS28(CRP)=0.56× √(TJC28)+0.28× √(SJC28)+0.36×(ln)(CRP+1)+0.014×PGA+0.96
SDAIScreening visit and all study visits (and all flare week visits, if applicable)SDAI=TJC28+SJC28+PhGA+PGA+CRP
CDAIScreening visit and all study visits (and all flare week visits, if applicable)CDAI=TJC28+SJC28+PhGA+PGA
HAQ-DIAll study visits starting from week 0 of lead-in period (and all flare week visits, if applicable)PRO to assess physical function and health-related quality of life of each patient
FACIT-fatigueEvery other visit starting from week 4 (ie, double-blind baseline and all flare week visits, if applicable)PRO to assess current fatigue
TSQMEvery other visit starting from week 4 (ie, double-blind baseline and all flare week visits, if applicable)PRO to assess satisfaction with current RA treatment
WPAIWeeks 4, 28 and 40 (and flare weeks 0, 10 and 16, if applicable)PRO to assess impact of RA on work productivity and non-work activity limitation
SF-36Weeks 4, 28 and 40 (and all flare week visits, if applicable)PRO to assess health and well-being
Physician and patient assessment of flare severityFlare week 0 onlyAssessed using a numeric rating scale ranging from 0 (not severe) to 10 (very severe)
RAPID-3All study visits starting from week 0 of the lead-in period (and all flare week visits, if applicable)Based on physical function, PGA of pain and patient global health
US (optional at investigator discretion)Week 0 or week 4 visit before randomisation (and at flare week 0 visit, if applicable)Systematic longitudinal and transverse multiplanar examination of 46 joints and 18 tendon/tendon compartments; each joint will be scored for B-mode synovial hypertrophy and synovial power Doppler signal on a scale of 0 to 3 (0=absent/no signal; 1=mild; 2=moderate; 3=marked) and tenosynovitis will be defined and scored according to the OMERACT
MRIWeek 0 of the lead-in period and the final/early termination visit (if last MRI≥12 weeks before and flare week 16, if applicable)MRI of the most affected hand (second to fifth MCP) and wrist or of the dominant hand and wrist (if both sides are considered equally affected)
BiomarkersWeeks 4, 10, 16, 28 and 40 (and flare weeks 0, 4 and 16, if applicable)Blood samples for the following biomarkers: MMP-3, C1M, C3M, CRPM, VICM, SAA, IL-6, CXCL-10, CXCL-13
Adalimumab concentrationWeeks 4, 10, 16, 28 and 40 (and flare weeks 0, 4, 10 and 16, if applicable)Blood sample for adalimumab concentration
Anti-adalimumab antibodiesWeeks 4, 10, 16, 28 and 40 (and flare weeks 0, 4, 10 and 16, if applicable)Blood sample for anti-adalimumab antibody levels
  • *Study visits comprise the following: screening visit, week 0 (lead-in period baseline), week 4 (double-blind baseline) and weeks 10, 16, 22, 28, 34 and 40 and early termination, if applicable. In case of a flare, study visits will subsequently consists of flare weeks 0 (ie, visit at which the flare is documented), 4, 10 and 16.

  • †The swollen and tender joint counts should be performed by a clinical assessor who will be blinded to the participants’ MRI and US results.

  • ‡Three-variable DAS28(ESR) can be used during the trial to evaluate flare (if the PGA score is not available) using the following formula: DAS28(ESR) = [0.56 × √(TJC28) +0.28 × √(SJC28) +0.70 × ln(ESR)]×1.08 + 0.16.

  • §Three-variable DAS28(CRP) can be used during the trial to evaluate flare (if the PGA score is not available) using the following formula: DAS28(CRP) = [0.56 × √(TJC28) +0.28 × √(SJC28) +0.36 × ln(CRP +1)]×1.10 + 1.15.

  • C1M, type I collagen neo-epitope; C3M, type III collagen neo-epitope; CDAI, Clinical Disease Activity Index; CRP, C reactive protein; CRPM, matrix metalloproteinase-degraded CRP; CXCL-10, chemokine (C-X-C motif) ligand 10; CXCL-13, chemokine (C-X-C motif) ligand 13; DAS28, Disease Activity Score based on 28 joints; ESR, erythrocyte sedimentation rate; FACIT, Functional Assessment of Chronic Illness Therapy; HAQ-DI, Health Assessment Questionnaire–Disability Index; IL-6, interleukin-6; ln, natural logarithm; MCP, metacarpophalangeal joint; MMP-3, matrix metalloproteinase 3; NA, no assessment; OMERACT, Outcome Measures in Rheumatology Clinical Trials; PGA, patient global assessment of disease activity; PhGA, physician global assessment of disease activity; PRO, patient-reported outcome; RA, rheumatoid arthritis; RAPID-3, Routine Assessment of Patient Index Data-3; SAA, serum amyloid-associated protein; SDAI, Simplified Disease Activity Index; SF-36, Short Form-36 Health Survey Questionnaire; SJC28, swollen joint count based on 28 evaluated joints; TJC28, tender joint count based on 28 evaluated joints; TSQM, Treatment Satisfaction Questionnaire for Medication; US, ultrasound; VAS, visual analogue scale; VICM, matrix metalloproteinase-degraded citrullinated vimentin; WPAI, Work Productivity and Activity Impairment.

  • ESR expressed as mm/hour and CRP expressed as mg/L.