Biologic therapy has been a major advance in the treatment of patients with immune diseases. Yet, it is clear that long-term disease management requires a more detailed understanding of factors that influence these drugs’ effectiveness. The authors confirm at least 10 years of observations that immunogenicity most notably with monoclonal antibody therapies results in treatment failure [1]. By contrast, receptor-based constructs seem less likely to be associated with the development of patient-derived antibody failure [2–4]. Also as pointed out by the authors, the development of neutralizing antibodies is independent of underlying immune disease. It is interesting to note that a recently commissioned consensus statement on biologic treatment of rheumatic disease mentioned immunogenicity two times (one time with regard to abatacept and the other time with regard to concomitant methotrexate). A simultaneous search for neutralizing antibodies was fruitless [5].

Long-term observations demonstrate that drop-off rates after institution of biologic treatment is high (likely greater that 50 %). The reasons thought to contribute to this drop-off rate include toxicity, compliance (cost), or loss of effect [6]. As presented in this paper, antibody formation may be as high as 30 % even if the antibody is humanized.

The implications of these findings include at least the following:

  1. 1.

    Moving forward will require a clinically acceptable assay system as an insurance carrier has suggested that present assay systems remain experimental in determining antibody/drug levels in rheumatic disease patients [7].

  2. 2.

    We need long-term data on durability of response using monotherapy with the monoclonal antibodies.

  3. 3.

    The ability of methotrexate, azathioprine, leflunomide, and mycophenolate to inhibit neutralizing antibody formation needs further clarification.

  4. 4.

    Drug developers should take into account the observation that monoclonal antibodies are prone to generate neutralizing antibodies.