Author Of 3 Presentations
P0085 - Harmonization of real-world studies in multiple sclerosis: retrospective analysis from the RIReMS group (ID 687)
Worldwide multiple sclerosis (MS) centers have coordinated their efforts to use data acquired in clinical practice for real-world observational studies.
In this retrospective study, we aim to harmonize outcome measures, and to evaluate their heterogeneity within the Rising Italian Researchers in MS (RIReMS) study group.
RIReMS members filled in a structured questionnaire evaluating the use of different outcome measures in clinical practice. Thereafter, thirty-four already-published papers from RIReMS centers were used for heterogeneity analyses, using the DerSimonian and Laird random-effects method to compute the between-study variance (τ2).
Based on questionnaire results, we defined basic modules for diagnosis and follow-up, consisting of outcome measures recorded by all participating centers at the time of diagnosis, and, then, at least annually; we also defined more detailed/optional modules, with outcome measures recorded less frequently and/or in the presence of specific clinical indications. Looking at heterogeneity, we found 5-year variance in age at onset (ES=27.34; 95%CI=26.18, 28.49; p<0.01; τ2=4.76), and 7% in female percent (ES=66.42; 95%CI=63.08, 69.76; p<0.01; τ2=7.15). EDSS variance was 0.2 in studies including patients with average age <36.1 years (ES=1.96; 95%CI=1.69, 2.24; p<0.01; τ2=0.19), or from 36.8 to 41.1 years (ES=2.70; 95%CI=2.39, 3.01; p<0.01; τ2=0.18), but increased to 3 in studies including patients aged >41.4 years (ES=4.37; 95%CI=3.40, 5.35; p<0.01; τ2=2.96). The lowest variance of relapse rate was found in studies with follow-up duration ≤2 years (ES=9.07; 95%CI=5.21, 12.93; p=0.02; τ2=5.53), whilst the lowest variance in EDSS progression was found in studies with follow-up duration >2 years (ES=5.41; 95%CI=3.22, 7.60; p=0.02; τ2=1.00).
We suggest common sets of biomarkers to be acquired in clinical practice, that can be used for research purposes. Also, we provide researchers with specific indications for improving inclusion criteria and data analysis, ultimately allowing data harmonization and high-quality collaborative studies.
P0094 - Inter-laboratory evaluation of cerebrospinal fluid and serum kappa free light chain measurements (ID 966)
The kappa index, calculated by dividing the cerebrospinal (CSF)/serum kappa free light chain (KFLC) ratio by the CSF/serum albumin ratio, is gaining increasing interest as an indirect marker of intrathecal activation of the humoral immune response. The demonstration of intrathecal synthesis is of particular relevance in the diagnostic work-up of suspected Multiple Sclerosis. However, the lack of consistent data on inter-laboratory agreement in CSF and serum KFLC measurements is one of the factors that hamper the use of kappa index in routine practice.
Aim of this study was to assess agreement in CSF and serum KFLC measurements and kappa index values across different laboratories.
Fifteen paired CSF and serum samples were analyzed in all participating laboratories (nr=8). Four centers used Binding Site instruments and assays, 3 centers used Siemens instruments and assays, and one center used a Siemens instrument and a Binding Site assay.
Absolute individual agreement between laboratories was calculated using a two-way mixed effects intraclass correlation coefficient (ICC). Cohen's kappa coefficient was used to measure inter-laboratory agreement on positive (≥5.8) kappa index values.
Within Binding Site laboratories, ICC for KFLC measurements was 0.96 (95%CI: 0.9-0.98) for CSF, 0.93 (95%CI: 0.63-0.98) for serum and 0.97 (95%CI: 0.94-0.99) for kappa index values. Within Siemens laboratories, ICC for KFLC measurements was 0.99 (95%CI: 0.97-100) for CSF, 0.93 (95%CI: 0.48-0.98) for serum and 0.95 (95%CI: 0.89-0.98) for kappa index values. ICC calculated for all laboratories was 0.93 (95%CI: 0.87-0.97) for CSF KFLC, 0.81 (95%CI: 0.53-0.93) for serum KFLC and 0.65 (95%CI: 0.43-0.84) for kappa index. Cohen's kappa coefficient for a positive kappa index was 0.89 across Binding Site laboratories, 0.70 across Siemens laboratories, and 0.77 across all laboratories.
There was an excellent agreement in CSF KFLC measurements and in kappa index values within laboratories using the same instrument and assay (Binding Site or Siemens), while serum KFLC measurements were less concordant. Agreement across all laboratories was decreased when including the laboratory using a Siemens instrument coupled with a Binding Site assay in the analyses. Concordance for a positive kappa index was substantial across all laboratories and within Siemens laboratories, and very good within Binding Site laboratories.
P0883 - MRI activity and extended interval of Natalizumab dosing: a multicenter Italian study (ID 1269)
- M. Clerico
- S. De Mercanti
- A. Signori
- M. Iudicello
- C. Cordioli
- E. Signoriello
- G. Lus
- S. Bonavita
- L. Lavorgna
- G. Maniscalco
- E. Curti
- L. Lorefice
- E. Cocco
- V. Nociti
- M. Mirabella
- D. Baroncini
- G. Mataluni
- D. Landi
- M. Petruzzo
- R. Lanzillo
- I. Gandoglia
- A. Laroni
- R. Frangiamore
- A. Sartori
- P. Cavalla
- G. Costantini
- M. Sormani
- R. Capra
Extending the natalizumab interval after the 24th administration could reduce the risk of progressive multifocal leukoencephalopathy (PML) without efficacy reduction.
To evaluate the non-inferiority of the efficacy of an extended interval dosing (EID) regimen compared with the standard interval dosing (SID) of natalizumab regarding the multiple sclerosis (MS) MRI activity.
It is an observational, multicenter (14 Italian centers), retrospective cohort study, starting from the 24th natalizumab infusion to the loss of follow-up or 2 years after baseline. Patients were grouped in 2 categories according to the mean number of weeks between doses: < 5 weeks, SID; ≥ 5 weeks, EID. Three hundred and eight patients were enrolled. Median dose interval (MDI) following 24th infusion was 5 weeks, with a bimodal distribution (modes at 4 and 6 weeks).
Two hundred and sixteen patients were in the SID group (MDI = 4.4 weeks) and 144 in the EID group (MDI 6 weeks). The risk to develop active lesions on MRI is similar in SID and EID groups during the 6 and 12 months after the 24th natalizumab infusion, respectively 2.98% (95% CI: 0.56-5.40) vs 3.32% (95% CI: 0.00-6.65%) [p=0.88] and 6.65% (95% CI: 3.02-10.29) vs 5.67% (95% CI: 1.76-9.58%) [p=0.73]. The EID regimen does not increase the occurrence of MRI activity after 6 and 12 months.
There is no evidence of a reduced efficacy of natalizumab in an EID setting regarding the MRI activity. This observation confirms previous clinical results and together with the increasing evidence of a reduced risk of PML associated to an EID regimen, supports the need of a bigger randomized study to assess the need to change the standard of the natalizumab dosing schedule, in order to better manage JCV-positive patients after 24 doses of natalizumab.