Background In the last years, the “treat to target” strategy revealed the importance of tight control of disease activity in RA patients1. To reach clinical remission or at least low disease activity as soon as possible, this strategy, now part of the EULAR guidelines, requires therapeutic combinations and/or fast switches between different therapies2. Over the last years it became clear that drug immunogenicity is one of the main mechanism behind biologic therapeutic failure3-4. How to integrate the notion of drug immunogenicity in clinical practice remains to be formally established. We conducted a systematic review of the Literature with a meta-analysis evaluating the clinical implications of drug immunogenicity5. Based on the information retrieved we designed a new algorithm which introduces immunogenicity assessment in the EULAR guidelines for the management of RA patients receiving biologic therapy.
Objectives We assessed the influence of adherence to our proposed algorithm on therapeutic responses and low disease activity rates in a prospective cohort of RA patients treated with biologics.
Methods We conducted a prospective cohort study over 2-years evolving 106 consecutive RA patients, 92% female, with a mean age of 55±13 yrs and mean disease duration of 6±4 yrs. Patients had been submitted to biologic therapy by a mean period of 4±3 years. Serum drug trough levels were assessed by ELISA and anti-drug antibodies (ADA) by an optimized Bridging ELISA, which we previously compared with a fluid-phase RIA. Clinicians were blind for the tests results. Therapeutic response and low disease activity were defined according to the EULAR guidelines.
Results At the study onset 22 patients were receiving Infliximab (36.4% anti-infliximab pos), 33 Adalimumab (27.3% anti-adalimumab pos) and 49 Etanercept (0% anti-etanercept pos). Patients with detectable ADAs had undetectable serum drug trough levels and lower therapeutic responses rates (37.5% vs 76.9%, p=0.001 for Infliximab and 33.3 vs 66.7%, p=0.02 for Adalimumab). Not a single patient with detectable ADAs had low disease activity. During follow-up period, therapeutic decision coincident with our proposed algorithm concerned 48.6% of the patients (Group 1), however with a décalage median (IQR) time of 249 days (116-388). Therapeutic decisions were discordant with our algorithm for 51.4% of the patients (Group 2). A significant higher proportion of patients in Group 1, when compared to Group 2, reached therapeutic response at 3 months (97.9% vs 52.2%, p=0.001) and at 12 months (71.4% vs 13% p=p=0.000). Moreover, a significant higher proportion of patients in Group 1 achieved low disease activity at 3 months (71.4% vs 13%, p=0.000) and at 12 months (58.8% vs 3.8%, p=0.000). Considering drug direct costs only, we evaluated that about 1 million euros were spent inefficiently in this cohort over 2 years.
Conclusions Our study strongly suggests that including immunogenicity assessment in EULAR guidelines will allow the design of more cost-effective strategies, tailored to each RA patient receiving biologic therapy.
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Bartelds et al. JAMA 2011;305:1460-8.
Jamnistski et al. Ann Rheum Dis 2011; 70:284-8.
EULAR 2012 Abstract: EULAR12-3348.
Disclosure of Interest None Declared