Answer:
Abatacept is a fusion protein of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), also designated CD152, and human IgG1. Abatacept binds to CD80 and CD86 on antigen presenting cells interfering with antigen specific T-cell activation via CD28, which also binds CD80 and CD86 resulting in a stimulatory signal to the T cell. The result is an immunosuppression that is useful in treating autoimmune diseases such as rheumatoid arthritis. This effect would not affect allergy skin testing or measurement of specific-IgE in vitro. To my knowledge there is no information with respect to allergen immunotherapy. Since specific T-cell regulatory stimulation is necessary for the benefits from immunotherapy, there is a theoretical argument that therapy with abatacept could reduce the effectiveness of the treatment. However, I do not see a reason that SCIT would be contraindicated with abatacept therapy. The issue of autoimmune disease and immunotherapy has been addressed in prior Ask the Expert questions (see below).
In summary, in my opinion abatacept (Orencia) therapy is not a contraindication for allergen testing or allergen immunotherapy.
Q: 6/28/2012
Pt has lupus, stable on cellcept/pred. Chronic sinus disease reagin mediated but also is IGA deficient I want to give her allergy shots what is the expert opinion.
A: Your question can be approached from two standpoints:
• Is there a contraindication to immunotherapy?
• Do any of the conditions you described have a potential effect on the efficacy of immunotherapy?
There are three features that appear in your description that bear mention in regards to both of the above parameters:
• IgA deficiency.
• The disease of systemic lupus erythematosus.
• The drugs mycophenolate mofetil and prednisone.
We will deal with each of these separately:
The issue of IgA deficiency, to my knowledge, has no known effect on the efficacy of immunotherapy nor does it represent a contraindication.
The issue of systemic lupus erythematosus is more complicated. The Parameters are moot on this issue, and certainly systemic lupus erythematosus is not a definite contraindication to immunotherapy, but some physicians feel that it is a relative contraindication. To my knowledge, however, there are no data in the literature to support this contention, and the objection to use of immunotherapy in "collagen vascular diseases," especially systemic lupus erythematosus, is, to the best of my knowledge, theoretical. There is also no evidence in the literature to indicate that this condition will have any effect on the efficacy of immunotherapy.
Thus, the issue of whether or not lupus is a relative contraindication to immunotherapy remains debatable, and there is no consensus of opinion to my knowledge in this regard and no evidence-based literature to refer to to help us make a decision.
Neither the administration of mycophenolate mofetil nor prednisone represents a contraindication to immunotherapy, but both theoretically could affect the response to immunotherapy. It is well known that mycophenolate mofetil can have an effect on antibody response (see Nephrol. Dial. Transplant abstract copied below) and therefore possibly reduce the efficacy of immunotherapy. However, there are no studies in this regard to substantiate that such an effect could occur during allergen immunotherapy.
The same is true for prednisone. We do know that long-term prednisone administration diminishes antibody levels (see JACI abstract copied below); however, the relative contribution of a diminished antibody synthesis versus catabolism has not been clearly delineated, and it may be that most of this effect is to increased catabolism rather than decreased production.
With all of this in mind, obviously we cannot give you a definitive answer, but can only highlight the issues involved, as we have done above, and give you an opinion.
In my personal opinion, systemic lupus erythematosus is not a contraindication to the administration of immunotherapy. We simply have no knowledge as to whether or not it may affect the response. Neither mycophenolate mofetil nor prednisone, as noted, is a definite contraindication to immunotherapy, but I feel that both, especially mycophenolate mofetil, may affect the efficacy of this treatment. I would not worry about administering immunotherapy in the presence of these drugs, but I believe that it should be explained to the patient that because of this treatment, there may be a diminished response to allergy injections.
Nephrol. Dial. Transplant. (1998) 13 (1): 160-164.doi: 10.1093/ndt/13.1.160
Abstract
Background: No conventional immunosuppressive agent preferentially inhibits antibody production. Studies in experimental animals and in human cells in vitro suggested mycophenolate mofetil (MMF) might have such an effect. If this was the case in vivo it could have significant implications in terms of both MMF toxicity and the rational design of immunotherapeutic regimens.
Methods: Subjects were renal transplant recipients (25 patients treated with prednisolone, cyclosporine and azathioprine, and 13 treated with prednisolone, cyclosporine and MMF) and 20 normal controls. The three groups received influenza vaccination, and the antibody response to it was measured 4¨C6 weeks later using a standard haemagglutination assay.
Results: MMF profoundly suppressed the humoral immune response to influenza vaccination when added to prednisolone and cyclosporine. This effect could be seen when comparing the rise in the mean titre of antibody after vaccination. It was also reflected in the number of patients mounting responses deemed to be clinically protective by either demonstrating a 4-fold rise in titre or an increase in titre to ¡Ý40.
Conclusions: Suppression of the humoral immune response by MMF has implications for the design of immunization protocols to protect the immuno-suppressed, and raises the possibility that MMF use may be accompanied by more or different infections than complicate more conventional immunosuppression. More importantly, consideration should be given to harnessing the relatively specific effect of MMF on antibody production to treat antibody-mediated diseases.
J Allergy Clin Immunol. 1978 Sep;62(3):162-6.
Settipane GA, Pudupakkam RK, McGowan JH. Corticosteroid effect on immunoglobulins.
The corticosteroid (prednisone) effect on serum immunoglobulins in 9 atopic asthmatic patients who required corticosteroids for the control of asthma was evaluated. Serum immunoglobulins were determined before corticosteroids were administered, an average of 15 days while on corticosteroids, and again an average of 22 days after corticosteroids were discontinued. While on corticosteroids (averaging 16.8 mg prednisone daily) for 15 days, mean serum IgG was significantly decreased (-22%, p less than or equal to 0.01), mean serum IgA tended to be decreased (-10%), and mean serum IgM was essentially unchanged. Serum IgE was initially significantly increased (p less than 0.01) when compared to levels of other serum immunoglobulins (IgG,A,M). An average of 22 days after corticosteroids were discontinued, mean serum IgG was still significantly decreased (p less than 0.05), and mean serum IgA again tended to be decreased. Serum IgM remained unchanged and mean serum IgE now was significantly decreased (p less than 0.01). Corticosteroids appear to have a significant effect on levels of some serum immunoglobulins.
Sincerely,
Phil Lieberman, M.D.
I hope this information is of help to you and your practice.
All my best.
Dennis K. Ledford, MD, FAAAAI