Reduction of Antidrug Antibody Levels after Switching to Rituximab in Patients with Rheumatoid Arthritis with Previous Failure to Infliximab or Adalimumab

Ana Martínez^1,2, Chamaida Plasencia^2,3, Victoria Navarro-Compán², Borja Hernández-Breijo², Dora Pascual-Salcedo², Pilar Nozal⁴, Cristina Diego⁴, Irene Monjo^2,3, Laura Nuño^3,5 and Alejandro Balsa^2,6, ¹Immunology. La Paz University Hospital, Madrid, Spain, ²Immuno-Rheumatology research group, IdiPaz. La Paz University Hospital, Madrid, Spain, ³Rheumatology, La Paz University Hospital, Madrid, Spain, ⁴La Paz University Hospital, Immunology, Madrid, Spain, ⁵Immuno-Rheumatology research group, IdiPaz. La Paz University Hospital, madrid, Spain, ⁶Hospital Universitario La Paz, Madrid, Spain

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: Adalimumab, infliximab, plasma cells, rheumatoid arthritis (RA) and rituximab

Session Information

Date: Tuesday, October 23, 2018

Title: 5T089 ACR Abstract: RA–Treatments IV: Strategy (2820–2825)

Session Type: ACR Concurrent Abstract Session

Session Time: 2:30PM-4:00PM

Background/Purpose:

Rituximab (Rtx) induces transient depletion of B cells. Previous data showed that Rtx is particularly effective on autoimmune diseases in which auto-antibodies (auto-Ab) are produced, such as rheumatoid arthritis (RA). It is hypothesized that plasma cells expressing CD20 could be targets of Rtx. Therefore, the immunogenicity related to the use of Infliximab (Ifx) or Adalimumab (Ada) could be cleared by Rtx.

The study aims were i) to analyze the persistence of anti-drug antibodies (ADA) after switching to a 2nd drug (TNFi, Rtx or Tocilizumab-Tcz-) after 24 months of follow-up and ii) to evaluate whether the reduction of ADA level is influenced by the mechanism of action of the second biological therapy (BT).

Methods: Dataset from a prospective cohort including all patients with RA starting BT in a tertiary hospital was used. For this study, data from 40 patients who failed to Infliximab (Ifx) (68%) or Adalimumab (Ada) (32%) related to ADA detection and then switched to a 2nd TNFi (Ifx, Ada, Etanercept or Certolizumab) or to Rtx or to Tcz were analyzed. Additionally, patients should have two determinations of ADA levels: one at the end of the first BT and at least another one at 6, 12 or 24 months after switching BT. ADA levels were determined by bridging ELISA. The proportion of patients with ADA negative levels at 6, 12 and 24 months was determined. Median ADA survival time (mst) performed by Kaplan-Meier curves was determined. The relative reduction (in median) of ADA levels at 6, 12 and 24 months respect to baseline was compared between the switching to different BT.

Results:

Out of 40 ADA positive patients with RA, 26 (65%) switched to a 2nd TNFi, 9 (23%) to Rtx and 5 (13%) to Tcz. Patients’ characteristics are shown in Table 1.

The percentage of patients with undetectable ADA levels was higher in the group of patients switching to Rtx or Tcz compared with patients switching to a 2nd TNFi (29% and 33% vs 8% at 12 months; 33% and 25% vs 8% at 24 months, respectively).

Moreover, undetectable ADA levels appears earlier in patients switching to Rtx (mst=12) than in patients switching to TNFi or Tcz (mst=24 in both BT).

The relative ADA reduction was higher in patients switching to Rtx than in patients switching to TNFi or Tcz. Reduction of median ADA levels at 6, 12 and 24 months were as follows: 80%, 75% and 92%, respectively for TNFi; 97%, 98% and 98% for Rtx and 25%, 84% and 67% for Tcz.

Conclusion: Despite discontinuing TNFi, ADA titters remain positive in a high proportion of patients with RA after 24 months of treatment with a second biologic. However, in patients receiving Rtx, ADA levels appear to decrease earlier and more patients became ADA negative than patients receiving TNFi or Tcz. This effect could be explained by the intrinsic action mechanism of Rtx on plasmatic CD20+ cells.

Table I: Demographics characteristics of the 40 patients according to the second biologic.

Switch to:	TNFi (n=26)	Rtx (n=9)	Tcz (n=5)	p
Women, n(%)	24 (92%)	6 (67%)	5 (100%)	0.08
Age, years, median (IQR)	44 (33.5-53.2)	51 (42.5-63.5)	52 (44-67.5)	0.09
Smokers, n (%)	10 (38%)	3 (33%)	1 (20%)	0.7
BMI, Kg/m², median(IQR)	24,7 (22.1-27)	31 (26.3-34.6)	25.9 (23-33.1)	0.05
MTX, n (%)	20 (77%)	6 (67%)	2 (40%)	0.2
Duration in previous biologic, median (IQR)	4.3 (1.3-7.84)	1.4 (1.1-3.6)	1.3(0.15-4.7)	0.08
Duration in second biologic, median (IQR)	2.3 (0.7-3)	1.75 (1-2)	1.96 (1-2,6)	0.2

Disclosure: A. Martínez, None; C. Plasencia, None; V. Navarro-Compán, None; B. Hernández-Breijo, None; D. Pascual-Salcedo, None; P. Nozal, None; C. Diego, None; I. Monjo, None; L. Nuño, None; A. Balsa, None.

To cite this abstract in AMA style:

Martínez A, Plasencia C, Navarro-Compán V, Hernández-Breijo B, Pascual-Salcedo D, Nozal P, Diego C, Monjo I, Nuño L, Balsa A. Reduction of Antidrug Antibody Levels after Switching to Rituximab in Patients with Rheumatoid Arthritis with Previous Failure to Infliximab or Adalimumab [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/reduction-of-antidrug-antibody-levels-after-switching-to-rituximab-in-patients-with-rheumatoid-arthritis-with-previous-failure-to-infliximab-or-adalimumab/. Accessed .

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