In this study, 28 patients with RA were included and treated with 400 mg CZP s.c. at weeks 0, 2 and 4 and every 2 weeks thereafter with 200 mg s.c.. Of these patients, all received CZP for at least 12 weeks, n = 27 (96.4%) until w24, and n = 18 (64.3 %) received CZP throughout the entire 52 weeks. The reasons for drop-out were withdrawal of CZP due to lack of efficacy (n = 9) or worsening of symptoms (n = 1). Fifteen patients were biologic naïve at inclusion. Thirteen patients had a history of biologic treatment. Sixteen patients were on background therapy with methotrexate, who received a mean dosage of 16 ± 4.28 mg per week and 23 patients with prednisolone. During the course of the study, the mean dosage of prednisolone decreased from 6.0 ± 4.75 mg per day to 3.9 ± 2.60 mg/d at w24 and 2.3 ± 2.26 mg/d at w52.

Patients’ characteristics at baseline are presented in Table 1.

Table 1 Baseline characteristics

Clinical and laboratory outcome parameters

Disease activity measured by DAS28 (CRP) continuously decreased from baseline to w52. At baseline, patients had a moderate to high disease activity with a median (min-max; IQR) DAS28 (CRP) of 4.6 (2.7–6.5; 1.8), which decreased under treatment to 3.2 (1.3–6.4;1.8; p = 0.001) at w24 and to 2.7 (1.2–4.9; 2.1; p < 0.001) at w52.

Similar results were observed for SJC-28 and TJC-28, which are also part of the DAS28 (CRP). Both outcome parameters continuously decreased from baseline to w52. For SJC-28, a decrease from median of 2.5 (0–9, 4.0) at baseline to 0.0 (0–6, 2.0; p = 0.005) at w24 and to 0.0 (0-6–1.8; p = 0.012) at w52 was observed. For TJC-28, a decrease from median of 7.0 (0–22, 8.8) at baseline to 3.0 (0–17, 4.0; p = 0.001) at w24 and to 2.0 (0–15, 3.5; p = 0.004) at w52 was observed.

Patient global assessment (VAS) decreased during the course of the study. Significant differences were observed at w6, w12 and w52. Similar results were observed for the global assessment performed by the physician.

Morning stiffness decreases continuously from baseline to w52 with significant findings at w6, w12 and w24.

CRP and ESR values continuously decreased from baseline to w52. The median CRP decreased from 5.4 mg/l (0.3–52; 17.4) to 2.3 mg/l (0.3–41; 5.5; p = 0.028) at w24 and to 2.0 mg/l (0.2–99; 5.0; p = 0.156) at w52. The median ESR decreased from 27 mm/h (8–66; 21) to 21 mm/h (2–70; 25.5; p = 0.203) at w24 and to 18 mm/h (2–54; 20; p = 0.177) at w52.

A summary of all measured clinical and laboratory outcome parameters is listed in Table 2.

Table 2 Summary statistics of clinical and laboratory outcome parameters at baseline and after w6, w12, w24 and w52

Fluorescence optical imaging (FOI)

The sum score of both hands in P1 of FOI continuously decreased from baseline to w52. A decrease in P1 of FOI sum score was already observed at w6, with a reduction from a median of 1.5 (0–16, 9.3) at baseline to 1.0 (0–12, 3; p = 0.069) at w6. The FOI P1 1 sum score further decreased to 0.5 (0–46, 3; p = 0.171), 0.0 (0-–0, 3; p = 0.004) and 0.0 (0–13, 2.8; p = 0.091) at w12, w24 and w52, respectively.

A statistically significant reduction was detected at w24. Although the sumscore from baseline to w52 decreased, the applied test did not yield a significant result. This likely occurred due to the reduced number of patients at that time point.

All other sum scores of both hands (PVM, P2 and P3) did not show a median reduction during the treatment.

The results of the FOI are presented in Table 3.

Table 3 Summary statistics of FOI phases 1-3 and PMV at baseline, w6, w12, w24 and w52

Figure 1 shows an example of a patient with good response to the CZP therapy which is displayed as a signal attenuation in comparison from baseline, visit 1 to week 52 in P1. The improvement of the inflammatory process can be seen in the significant decrease of early enhancement in both hands during the treatment period.

Fig. 1
figure 1

Fluorescence optical imaging illustrations in phase 1. A Baseline visit. FOI findings with clinical active RA. Increased signal intensities as a sign of active inflammation in P1. High signal intensities (FOIAS grade 3) in PIP5 of the right hand, moderate signal intensities (FOIAS grade 2) in both wrists and PIP4 of the right and PIP5 of the left hand. B After 52 weeks of CZP treatment; no increased signal intensities are detectable

Musculoskeletal ultrasound

For GS, a numerical decrease of the US7 synovitis sum score was only observed at w52 (from 11.0 at baseline to 8.5 at w52).

For PD, a numerical decrease of the US7 synovitis score was detected at w12 (from 2.0 to 1.5) with a further decrease at w52 (to 0.5).

For GS tenosynovitis und PD tenosynovitis US7 scores, no relevant changes could be detected throughout the study.

The outcome parameters of the GS and PD US7 synovitis/tenosynovitis scores are presented in the Supplement Table S1 at baseline and after 6, 12, 24 and 52 weeks of therapy with CZP.

A visual summary of the results is provided in Supplement Figure S2 which presents box plots of DAS28, FOIAS P1, GS, PD, SJC-28 and TJC-28 at baseline, w6, w12, w24 and w52.

Correlation of FOIAS with selected clinical and US7 score outcome parameters

Regarding baseline data, FOIAS in PMV and P1, P2 P3 showed no significant positive correlations with any clinical outcome parameter. There was a moderate correlation between FOIAS P3 with PD US7 synovitis score. All other US7 Score parameters showed a weak or no positive correlation with FOIAS in PMV and P1, P2, P3.

At week 24, there was a moderate correlation between FOIAS in P2 with DAS28 and with TJC-28. All other clinical parameters showed weak or no positive correlation with FOIAS in PMV and P1, P2, P3. No significant correlation could be presented between FOIAS in PMV and P1, P2, P3 with all US7 Score parameters.

At week 52, FOIAS P2 showed a moderate correlation with TJC-28. There was a moderate correlation between FOIAS P2, P3, PVM and PD synovitis score and a moderate correlation between FOIAS P3, PVM and PD tenosynovitis score.

Pairwise correlations between clinical and laboratory outcomes with FOIAS P1-P3 and PMV as well as with US7 Score parameters are presented in Figure S1 (supplement).

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