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First exposure to r...
First exposure to rituximab is associated to high rate of anti-drug antibodies in systemic lupus erythematosus but not in ANCA-associated vasculitis
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- Faustini, Francesca (författare)
- Karolinska Institutet,Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden
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- Dunn, Nicky (författare)
- Karolinska Institutet,Karolinska Inst, Sweden; Ctr Mol Med, Sweden
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- Kharlamova, Nastya (författare)
- Karolinska Inst, Sweden; Ctr Mol Med, Sweden
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- Ryner, Malin (författare)
- Karolinska Inst, Sweden; Ctr Mol Med, Sweden
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- Bruchfeld, Annette (författare)
- Linköpings universitet,Avdelningen för diagnostik och specialistmedicin,Medicinska fakulteten,Region Östergötland, Njurmedicinska kliniken US,Karolinska Univ Hosp, Sweden; Karolinska Univ Hosp, Sweden; CLINTEC Karolinska Inst, Sweden
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- Malmström, Vivianne (författare)
- Karolinska Institutet,Karolinska Inst, Sweden; Ctr Mol Med, Sweden
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- Fogdell-Hahn, Anna (författare)
- Karolinska Institutet,Karolinska Inst, Sweden; Ctr Mol Med, Sweden
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- Gunnarsson, Iva (författare)
- Karolinska Institutet,Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden
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(creator_code:org_t)
- 2021-08-13
- 2021
- Engelska.
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Ingår i: Arthritis Research & Therapy. - : BMC. - 1478-6362. ; 23:1
- Relaterad länk:
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https://liu.diva-por... (primary) (Raw object)
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https://arthritis-re...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- Background Anti-drug antibodies (ADAs) can impact on the efficacy and safety of biologicals, today used to treat several chronic inflammatory conditions. Specific patient groups may be more prone to develop ADAs. Rituximab is routinely used for ANCA-associated vasculitis (AAV) and as off-label therapy for systemic lupus erythematosus (SLE), but data on occurrence and predisposing factors to ADAs in these diseases is limited. Objectives To elucidate the rate of occurrence, and risk factors for ADAs against rituximab in SLE and AAV. Methods ADAs were detected using a bridging electrochemiluminescent (ECL) immunoassay in sera from rituximab-naive (AAV; n = 41 and SLE; n = 62) and rituximab-treated (AAV; n = 22 and SLE; n = 66) patients. Clinical data was retrieved from medical records. Disease activity was estimated by the SLE Disease Activity Index-2000 (SLEDAI-2 K) and the Birmingham Vasculitis Activity Score (BVAS). Results After first rituximab cycle, no AAV patients were ADA-positive compared to 37.8% of the SLE patients. Samples were obtained at a median (IQR) time of 5.5 (3.7-7.0) months (AAV), and 6.0 (5.0-7.0) months (SLE). ADA-positive SLE individuals were younger (34.0 (25.9-40.8) vs 44.3 (32.7-56.3) years, p = 0.002) and with more active disease (SLEDAI-2 K 14.0 (10.0-18.5) vs. 8.0 (6.0-14), p = 0.0017) and shorter disease duration (4.14 (1.18-10.08) vs 9.19 (5.71-16.93), p = 0.0097) compared to ADA-negative SLE. ADAs primarily occurred in nephritis patients, were associated with anti-dsDNA positivity but were not influenced by concomitant use of corticosteroids, cyclophosphamide or previous treatments. Despite overall reduction of SLEDAI-2 K (12.0 (7.0-16) to 4.0 (2.0-6.7), p < 0.0001), ADA-positive individuals still had higher SLEDAI-2 K (6.0 (4.0-9.0) vs 4.0 (2.0-6.0), p = 0.004) and their B cell count at 6 months follow-up was higher (CD19 + % 4.0 (0.5-10.0) vs 0.5 (0.4-1.0), p = 0.002). At retreatment, two ADA-positive SLE patients developed serum sickness (16.7%), and three had infusion reactions (25%) in contrast with one (5.2%) serum sickness in the ADA-negative group. Conclusions In contrast to AAV, ADAs were highly prevalent among rituximab-treated SLE patients already after the first course of treatment and were found to effect on both clinical and immunological responses. The high frequency in SLE may warrant implementations of ADA screening before retreatment and survey of immediate and late-onset infusion reactions.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)
Nyckelord
- Rituximab; Anti-drug antibodies (ADA); Systemic lupus erythematosus; ANCA-associated vasculitis; Disease activity; B cell counts; ADA-screening
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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