HANDSCAN OPTICAL MEASUREMENTS IN RHEUMATOID ARTHRITIS: AN INVENTORY COMPARING SERUM LEVELS OF CRP, ESR, IL-6, CLINICAL ARTHRITIS AND REPRODUCIBILITY OF DAS28.

A better tool for monitoring disease activity in RA is necessary for several reasons.
The Handscan is a new (Dutch) non invasive imaging device that visualizes inflammation in the joints of hands and wrists in patients with rheumatoid arthritis (RA). The technique is based on optical spectral transmission measurements. By using this technique, the Handscan is supposed to be an objective measurement tool. We will elaborate on the underlying physiological principles, practical set up and use of the Handscan in Chapter 7.
The Handscan already demonstrated its ability to visualize subclinical inflammation when compared to ultrasound imaging and DAS28 scores (1)
At this time, only a few institutes (including MCL and LUMC) have access to and experience with this new device. Until now there are no data comparing the Handscan with systemic parameters of inflammation, such as ESR, CRP, IL-6 and arthritis activity. Also, the range of the optical score in different patients is not known.
With this study proposal we will gather data, which may lead to more specific clinical Handscan studies. First we have to define its association with current objective inflammatory parameters and its quality to sense small (subclinical) changes in a short treatment period. If this quality exists, than the Handscan might be a new tool for objective and better measurement of disease activity. Preliminary data suggest that the Handscan is more sensitive to change than clinical examination. If persistence of subclinical arthritis may be an indicator of difficult to treat disease, one intriguing application could be the use of the Handscan as a classification tool for early patients, who would benefit most from rapid onset initiation of biologic treatment at the beginning of the disease.
Furthermore, use of the Handscan as an instrument for substitution of medical healthcare workers in controlling disease activity could be an important answer to the expected shortage of healthcare workers in rheumatology.
Study design: Randomized open label trial.
Study population: Early MTX naive RA patients, who will be randomized in three subgroups: I. methotrexate monotherapy, II. methotrexate plus depomedrol and III. methotrexate plus Sarilumab.
Main study parameters/endpoints:
Describing the association between Handscan optical scores and markers of inflammation (levels of CRP, serum IL-6) and clinical swollen joint score in three treatment groups with different pharmacokinetic modes of action for RA activity. Each of these groups has its own time to response due to differences in pharmacodynamic properties of the used medication. If the Handscan is really sensitive to early response then a difference in Handscan scores between treatment groups should be detected.
Secondary endpoints are:
- a comparison of differences in time to response between the three treatment groups for swollen joint count, tender joint count, DAS28, CRP, ESR and IL-6
- Defining the Handscan optical scores in untreated early RA patients at baseline
- Establish reproducibility of Handscan measurements with interobserver variability of DAS28.
- Association between Handscan total optical score and DAS28
- Describing the effects of Sarilumab therapy in MTX naïve patients compared to the monotherapy MTX group
- Establish IL-6 levels with rate of severity of arthritis activity, DAS28 categories

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Six visits (week 0, 1, 3, 6, 9 12), with three Handscans at each visit. DAS28 scores will be performed by three independent assessors at each visit. Blood samples for ESR, CRP and IL-6 at each visit. There is no additional discomfort associated with the Handscan and no sequels or further complications are involved. Sarilumab in combination with MTX is not yet registered for prescription in MTX naïve patients, however we judge that this combination can safely be administered in this group of RA patients. As a benefit, experimental data obtained through this experiment may result in validating the Handscan as a diagnostic tool.

First we have to define its association with current objective inflammatory parameters and its quality to sense small (subclinical) changes in a short treatment period. If this quality exists, than the Handscan might be a new tool for objective and better measurement of disease activity. Preliminary data suggest that the Handscan is more sensitive to change than clinical examination. If persistence of subclinical arthritis may be an indicator of difficult to treat disease, one intriguing application could be the use of the Handscan as a classification tool for early patients, who would benefit most from rapid onset initiation of biologic treatment at the beginning of the disease.

week 1 (early), week 3 (early), week 6 (intermediate), week 9 (late), week 12 ( late)

Early MTX naive RA patients will be randomized in three subgroups: I. methotrexate monotherapy, II. methotrexate plus depomedrol and III. methotrexate plus Sarilumab.
After randomisation the study is an open label observational study, which focusses on the characteristics of different modes for scoring RA disease activity during 12 weeks.

In this study the Handscan is used as an investigational product and is compared to current methods for quantification of disase activity in Rheumatoid Arthritis, such as physical examination (clinical judgement) of a rheumatologist and composite scores of disease activity such as DAS28, ACR response criteria and laboratory measurements as CRP en ESR.