104 CHAPTER 5 No correlation of depletion and treatment outcome To answer the question whether timing of B-cell depletion correlates with treatment efficacy, we evaluated changes in DAS28 and clinical response separately in patients who had their first post-depletion timepoint within one month after treatment (early depleting group), and patients who achieved this endpoint later during the follow-up (late depleting group). Interestingly, while achieving the post-depletion timepoint at one month, patients in the early depleting group did not show any change in DAS28 at this timepoint. In contrast, late depleting patients did show a decrease in DAS28-score one-month post-treatment, significantly different from that in early depleting patients (median (IQR): -0.9 (-1.7 – 0.0) vs. 0.0 (-0.7 – 0.2); p-value = 0.04); Figure 3A and online supplementary figure S3A excluding imputed data). This effect was still observed after 3 months (-1.5 ± 0.8 vs. -0.50 ± 1.1; p-value = 0.02; Figure 3B and online supplementary figure S3B). At month 6 or 12 the groups did not show significant differences in changes in DAS28 and in clinical response (data not shown). Taken together these data indicate that timing of depletion is not correlated to long-term therapy response, and suggest that a delayed achievement of B-cell depletion after treatment might be associated with reduced disease activity in the first three months. Figure 3 |Timing of depletion does not predict long-term clinical outcome but correlates with short-term disease activity A-B) Boxplot showing the changes in DAS28-score between month 1 (A) or month 3 (B) post-treatment and baseline in early or late depleting patients Boxplots show the median and 25th and 75th interquartile, error bars show the range, and single data points are depicted in grey (*p ≤ 0.05, using Mann-Whitney test in A and unpaired t-test in B). Correlation of repopulation with treatment outcome Next, we evaluated whether the timing of repopulation of the B-cell compartment is correlated with treatment outcome. Patients were divided into an “early” or “late” repopulation group, with early repopulating patients having their first post-repopulation timepoint within 6 months after treatment. Compared to baseline, no dif-
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