HEalthy Living in Inflammatory Arthritis (HELIA trial): a randomized controlled trial comparing efficacy between an interactive, online lifestyle intervention program and general nutrition recommendations

The primary outcome is the proportional difference in DAS28/DAPSA remission

and/or those who were able to taper their medication without having a disease

flare after 12 months of follow-up between inflammatory arthritis patients who

followed the lifestyle intervention program and those who received general

nutrition recommendations. Disease activity in rheumatoid arthritis (RA) and

psoriatic arthritis (PsA) patients is respectively measured with the DAS28 and

DAPSA. The DAS28 is a pooled index that involves the incorporation of an

28-joint count for tenderness (TJC28), a 28-joint count for swelling (SJC28),

an erythrocyte sedimentation rate (ESR) and general health (GH, measured with a

VAS 0 -100mm) into a formula to obtain a numerical indicator of disease

activity. The DAS28 formula is 0.56*(TJC28) + 0.28*(SJC28) + 0.70ln(ESR) +

0.014(GH). The DAPSA is also a pooled index, which is made up following 5

domains: (1) a 68-joint count for tenderness, (2) a 66-joint count for

swelling, (3) a C-reactive protein (expressed in mg/dl),(4) a patient*s

assessment of the disease activity (VAS, 0 - 10 cm) and (5) a patient*s

assessment of pain severity (VAS, 0 - 10 cm). The numerical values for the

aforementioned 5 domains are summed to provide the DAPSA score. Thresholds for

remission are respectively <2.6 and <=4. Tapering of treatment is left to the

discretion of the treating rheumatologist and patient.



The co-primary outcome for the cost-effectiveness analysis will be the

incremental cost-effectiveness ratio (ICER), which is the ratio of the

difference in costs to incremental benefits between the online interactive

lifestyle intervention program and general nutrition recommendations. For the

cost-effectiveness analysis we will calculate the Quality Adjusted Life Years

(QALYs) and total costs. QALYs express the impact of the disease on patients*

health over time. Living in perfect health corresponds to a QALY of 1, a QALY

of 0 reflects death. QALYs are determined by calculating the area under the

curve of dutch EuroQol questionnaire with 5 dimensions (EQ-5D) with 5 levels.

Costs are divided in direct and indirect costs. We will analyse direct and

indirect costs from a societal perspective. Direct costs are the costs of

treatment and medical consumption, whereas indirect costs are costs due to loss

of productivity (i.e. presenteeism and absenteeism). Medication costs are

calculated from doses reported in the patients* case records, valued according

to the Dutch college of health insurances. Medical consumption, including

duration of hospitalizations and admission diagnosis are recorded every three

months with the iMTA medical consumption questionnaire. We will use the Dutch

average length of stay by diagnosis if the duration of hospitalization is

unknown. Indirect costs include not fully functioning, sick leave and reduction

in work time. Worker productivity is measured with the Work Productivity and

Activity Impairment (WPAI) questionnaire, which includes presenteeism and

absenteeism. WPAI outcomes are expressed as impairment percentages, with higher

numbers indicating greater impairment and less productivity.

For our secondary endpoints the effectiveness from a clinical, patient as well

as a societal point of view, will be compared between the online interactive

lifestyle intervention program and general nutrition recommendations.



Clinical outcomes:

• In rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients disease

activity (states) are respectively measured with the DAS28 and DAPSA. The DAS28

is a pooled index that involves the incorporation of an 28-joint count for

tenderness (TJC28), a 28-joint count for swelling (SJC28), an erythrocyte

sedimentation rate (ESR) and general health (GH, measured with a VAS 0 -100mm)

into a formula to obtain a numerical indicator of disease activity. The DAS28

formula is 0.56*(TJC28) + 0.28*(SJC28) + 0.70ln(ESR) + 0.014(GH). The DAPSA is

also a pooled index, which is made up following 5 domains: (1) a 68-joint count

for tenderness, (2) a 66-joint count for swelling, (3) a C-reactive protein

(expressed in mg/dl), (4) a patient*s assessment of the disease activity (VAS,

0 - 10 cm) and (5) a patient*s assessment of pain severity (VAS, 0 - 10 cm).

The numerical values for the aforementioned 5 domains are summed to provide the

DAPSA score. Thresholds for remission and moderate-to-high disease activity are

respectively <2.6 and <=4 and >=3.2 and >14.



Patient reported outcomes (PROs):

• Self-reported disease activity, measured with the Routine Assessment of

Patient Index Data 3 (RAPID3). Thresholds for remission and moderate-to-high

disease activity are respectively <3.1 and >=6.1 if the 0 - 30 scale is used.

• General Health, measured with a visual analogue scale (VAS, 0 - 100 mm),

whereby higher scores reflect greater severity.

• Pain, measured with a visual analogue scale (VAS, 0 - 100 mm), whereby higher

scores reflect greater severity.

• Morning stiffness (severity and duration), measured with a 10-point Likert

scale, whereby higher scores reflect greater severity.

• Fatigue, measured with the Functional Assessment of Chronic Illness Therapy -

Fatigue (FACIT-F). The FACIT-F consists of 13-items with a 7-day recall period.

Items are scored on a 0 - 4 response scale with anchors ranging from *Not at

all* to *Very much so*. All items are summed to create a single fatigue score

with a range from 0 to 52 and higher scores represent less fatigue.

• Fatigue, measured with a visual analogue scale (VAS, 0 - 100 mm), whereby

higher scores reflect greater severity.

• Functional ability, measured with the health assessment questionnaire (HAQ).

Higher HAQ scores indicate poorer function.

• Quality of life, measured with the Dutch EuroQol questionnaire with 5

dimensions (EQ-5D) with 5 levels. Higher scores represent a higher quality of

life.

• Quality of sleep, measured with the sleep scale from the medical outcomes

study (MOS-ss). The MOS-ss includes 12 items assessing sleep disturbance, sleep

adequacy, somnolence, quantity of sleep, snoring, and awakening. A sleep

problems index, grouping items from each of the former domains, is also

available.

• Diet compliance, measured with a self-developed questionnaire consisting of

17 questions.



Societal outcomes:

• Worker productivity, measured with the Work Productivity and Activity

Impairment (WPAI) questionnaire,which includes presenteeism and absenteeism.

WPAI outcomes are expressed as impairment percentages, with higher numbers

indicating greater impairment and less productivity.