Prognostic Utility of Antibodies to Adalimumab in RA, AS, and PsA

Adalimumab is a subcutaneously administered recombinant fully human monoclonal antibody that inhibits tumor necrosis factor.  It has been approved by the US Food and Drug Administration for use in rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), and Crohn’s disease.

In a study published in Joint Bone Spine, Hoxha and colleagues evaluated the significance of the formation of anti-adalimumab (anti-ADA) antibodies to clinical disease burden and diagnostic laboratory features in RA, AS, and PsA.¹ The 24-week open-lab prospective multicenter study included patients who had a diagnosis of RA, AS , or PsA for at least 6 months, with disease activity as defined by a 28-joint Disease Activity Score-CRP (DAS 28-CRP) ≥3.2 and a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score ≥4. The investigators recruited 58 adalimumab-naive patients (35 women, 23 men) with a mean age of 45.9 years and a mean disease duration of 89.2 months.  The participants were all given adalimumab 40 mg every 2 weeks.

Blood samples measuring anti-ADA antibodies, antinuclear antibodies (ANA), antidouble stranded DNA antibodies,  antiextractable nuclear antigens (anti-ENA), and antiphospholipid antibodies (aPL) were obtained at baseline and then at 4, 12, and 24 weeks after initiation of treatment.

The researchers found that anti-ADA antibodies were associated with treatment failure (odds ratio [OR] 4.5; 95% confidence interval [CI]: 1.1-18.2) and that anti-ADA antibodies arose in 6 out of 21 (28.6%) patients with RA, 4 out of 22 (18.2%) patients with ankylosing spondylitis, and 1 out of 15 (6.7%) patients with PsA. They concluded that patients who developed measurable anti-ADA antibodies were less likely to benefit from treatment.  These data are consistent with previous studies that reported an association between the generation of antidrug antibodies and a decreased response to treatment in RA and AS.² It is important to note that this study was limited by small study size and included patients with different inflammatory disease states (RA, PsA, or AS), of which a subset received concomitant methotrexate therapy, which could have confounded results. 

Summary and Clinical Applicability

In this study, the researchers concluded that patients who developed antibodies to adalimumab were less likely to benefit from treatment.  If this is further confirmed with larger studies, antibodies to adalimumab may serve as an early prognostic indicator of poor clinical response to adalimumab treatment.

References

1. Hoxha A, Calligaro A, Tonello M, et al. The clinical relevance of early anti-adalimumab antibodies detection in rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis: A prospective multicentre study. Joint Bone Spine. 2015; Dec 29. pii: S1297-319X(15)00253-5. doi: 10.1016/j.jbspin.2015.04.020. [Epub ahead of print]

2. de Vries MK, Brouwer E, van der Horst-Bruinsma IE, et al. Decreased clinical response to adalimumab in ankylosing spondylitis is associated with antibody formation. Ann Rheum Dis. 2009;68:1787-1788.