Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose: Blocking TNF alpha (TNFα) with monoclonal antibodies (mAbs) has been successful in the treatment of rheumatoid arthritis. However secondary resistances are frequent and impose treatment changes. Active immunization with a TNF-Kinoid that safely induces self polyclonal anti-TNFα antibodies (Abs) could be an alternative to anti-TNFα mAbs. We evaluated the immunogenicity and safety of TNF-K in patients with rheumatoid arthritis and secondary resistance to TNF blockers.
Methods: TNFα-Kinoid (TNF-K, Neovacs SA, Paris, France) is an immunotherapeutic composed of recombinant human TNFα conjugated to KLH, inactivated and adjuvanted with ISA-51 emulsion. 40 patients with active rheumatoid arthritis (DAS28≥3.2) with history of positive clinical response to at least one TNF-blocker followed by secondary failure (35% IFX, 30 % ADA, 42.5% ETA) were enrolled in a double-blind, placebo-controlled, phase 2 study to evaluate three different intramuscular doses of TNF-K (90, 180, 360 mcg) and two immunization schedules (D0 and 28 or D0, 7 and 28). Humoral immune responses were evaluated through titration of anti-TNFα and anti-KLH Abs and neutralization assay. The T cell response was assessed by lymphoproliferative assay with tritiated thymidine incorporation. Clinical response was evaluated by the ACR and EULAR core set response.
Results: No related serious adverse event has been reported. Few minor transient local and systemic reactions have been recorded following immunization. Anti-TNFα Abs were induced in 50%, 75% and 91% of patients at 90 mcg, 180 mcg and 360 mcg, respectively. 100% of patients with three injections of 180 or 360 mcg had immunogenic response against TNF versus 67% in the groups receiving two injections. The anti-TNF antibody geometric mean titres were higher in patients who received 3 injections of 360 mcg. No lymphoproliferative response could be measured after stimulation with native TNF. Among the 21 patients who developed anti-TNF Abs, 48% present a moderate to good response according to EULAR score as opposed to only 31% of the 16 patients without Abs. A mean decrease of -14% of the C reactive protein level is measured in patients with Abs while in patients without Abs, the mean CRP level increased by 5%.
Conclusion: Active immunization with TNFα kinoid to induce a polyclonal, self-anti-TNFα antibody response is safe and immunogenic. A clear dose-response was observed for the dose of kinoid as well as for the number of administrations. Association of anti-TNF Abs induced by the kinoid with clinical and biological responses were observed in patients included in this preliminary phase 2 study. Further studies are needed to confirm this new approach in RA.
Disclosure:
P. Durez,
None;
P. Miranda,
None;
A. Toncheva,
None;
A. Berman Sr.,
None;
O. L. Rillo,
None;
Y. Boutsen,
None;
T. Kehler,
None;
E. Mociran,
None;
L. Soto Saez,
None;
B. Fautrel,
None;
X. Mariette,
Neovacs SA,
5;
P. Solakov,
None;
E. Lucero,
None;
T. Vlak,
None;
S. Grazio,
None;
K. Mastrovic,
None;
R. Chiriac,
None;
G. Grouard-Vogel,
Neovacs SA,
3;
O. Dhellin,
Neovacs SA,
3;
S. Ouary,
Neovacs SA,
3;
P. Vandepapeliere,
Neovacs SA,
3;
M. C. Boissier,
Neovacs SA,
5.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/active-immunization-with-tnf-kinoid-in-rheumatoid-arthritis-patients-with-secondary-resistance-to-tumor-necrosis-factor-alpha-antagonists-is-safe-and-immunogenic/