As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to golimumab in the trials described below with the incidence of antibodies in other trials or to other products may be misleading.

Results from the EIA Method

Using an enzyme immunoassay (EIA method), antibodies to golimumab were detected in 57 (4%) of SIMPONI-treated patients across the Phase 3 RA, PsA and AS trials through Week 24. Similar rates were observed in each of the 3 indications. Patients who received SIMPONI with concomitant MTX had a lower proportion of antibodies to golimumab than patients who received SIMPONI without MTX (approximately 2% vs. 7%, respectively).

With the EIA method, the presence of serum concentrations of golimumab can interfere with the detection of antibodies to golimumab leading to inconclusive results. In UC trials, 34 (3%), 341 (28%) and 823 (69%) of SIMPONI-treated patients were positive, negative and inconclusive for antibodies to golimumab, respectively. Treatment with concomitant immunomodulators (AZA, 6-MP or MTX) resulted in a lower proportion of patients with antibodies to golimumab than patients receiving SIMPONI without immunomodulators (2% vs. 4%, respectively).

Of the patients with a positive antibody response to golimumab in the Phase 2 and 3 trials, most were determined to have neutralizing antibodies to golimumab as measured by a cell-based functional assay.

Results from the Drug-Tolerant EIA Method

A drug-tolerant enzyme immunoassay (drug-tolerant EIA) method for detecting antibodies to golimumab was developed and validated, which eliminated the inconclusive category as reported above. This method is approximately 16-fold more sensitive than the original EIA method with less interference from golimumab in serum.

Based on the drug tolerant EIA method, 246 (23%) of SIMPONI-treated patients across the Phase 3 RA, PsA and AS trials, antibodies to golimumab were detected in 59 (16%), 106 (28%), and 81 (24%) patients, respectively. Treatment with concomitant MTX resulted in a lower proportion of patients with antibodies to golimumab than in patients receiving SIMPONI without MTX in RA patients (7% vs. 35%), in PsA patients (18% vs. 38%) and in AS patients (6% vs. 29%). A trend of decreasing drug concentrations with increasing antibody titers was observed. While an overall decrease in clinical efficacy for ADA positive patients compared with ADA negative patients was not observed in patients with RA (ACR 20: 75% vs. 75%), PsA (ACR 20: 72% vs. 66%) and AS (ASAS 20: 57% vs. 65%), higher titer antibodies may be associated with diminished efficacy.

In the UC trials, 254 (21%) of SIMPONI-treated patients were positive for antibodies to golimumab through week 54 while the remaining 941 (79%) patients were negative. Treatment with concomitant immunomodulators (AZA, 6-MP or MTX) in the UC trials resulted in a lower proportion of patients with antibodies to golimumab than in patients receiving SIMPONI without immunomodulators (12% vs. 26%). There is a trend of decreasing drug concentrations with increasing antibody titers. Although the development of antibodies to golimumab did not preclude clinical response, a trend toward decreased efficacy in ADA positive patients was observed compared to ADA negative patients in the UC trials (clinical response 38% vs. 53%).