Antidrug Antibodies Hinder Adalimumab Effect in PsA

Sep 03, 2014

Patients with psoriatic arthritis fare much worse on adalimumab (Humira) if antibodies begin to react against the drug.

Vogelzang EH, Kneepkens EL, Nurmohamed MT, et al., Anti-adalimumab antibodies and adalimumab concentrations in psoriatic arthritis; an association with disease activity at 28 and 52 weeks of follow-up.Ann Rheum Dis. (2014) doi:10.1136/annrheumdis-2014-205554. Online first Aug 12, 2014

For psoriatic arthritis (PsA) patients who don't respond well to adalimumab (Humira), the explanation may be antidrug antibodies (ADAs), judging from work by researchers in the Netherlands who found significantly worse outcomes among those who had any detectable levels.

The study involved 103 consecutive PsA patients at an Amsterdam rheumatology clinic treated with adalimumab. It found lower concentrations of the drug and higher levels of inflammatory markers among the 23 patients who developed ADAs. They also had higher disease activity in 28 joints (DAS28) and Psoriasis Area and Severity Index (PASI) scores.

The patients, all around age 50 (equal numbers of men and women), had received 40 mg subcutaneous adalimumab every other week, either as monotherapy or in combination with disease modifying antirheumatic drugs (DMARDs), with or without prednisone.

A consistent pattern emerged in all clinical outcome variables: those patients with detectable ADAs had a poorer clinical outcome at weeks 28 and 52 than patients without detectable ADAs. Median adalimumab concentrations were markedly lower in those with ADAs: 1.3 mg/L vs 8.7 mg/L at 28 weeks and only 0.9 mg/L vs 9.4 mg/L at 52 weeks (see chart). [[{"type":"media","view_mode":"media_crop","fid":"27513","attributes":{"alt":"anti-adalimumab antibodies in psoriatic arthritis","class":"media-image media-image-right","id":"media_crop_1178856830172","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"2692","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"width: 294px; height: 177px; float: right; margin: 2px;","title":" ","typeof":"foaf:Image"}}]]

Levels of C reactive protein (CRP) and erythrocyte sedimentation rates (ESR) rose as serum drug levels declined, suggesting that low levels of adalimumab can’t effectively block TNFα.

Based on these findings, the researchers suggest an optimal adalimumab concentration range for PsA patients between 5 mg/L and 8 mg/L. Doses could be tapered for those with low disease activity and higher serum drug levels, they add.

A previous study involving patients with in peripheral spondyloarthritis  found no clear association between ADAs and serum adalimumab levels, clinical response to treatment, or relapse after treatment discontinuation. However, an earlier study by authors from the same institutions as this one found the test positively associated with non-response to adalimumab in rheumatoid arthritis patients.

The current study used an assay developed by the Dutch firm Sanquin to determine ADA levels. An anti-adalimumab antibody test using a related method is available from LabCorp in the United States.

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