Tuesday, 6 December 2011

NABs: what about the long-term implications?

"At the recent European Charcot Foundation meeting in Marbella, Spain, on "Towards Personalized Treatment in Multiple Sclerosis" a large part of  the programme was devoted to biomarkers (biological markers). The one biomarker that was discussed in some detail was neutralising anti-interferon beta antibodies or NABs. NABs develops in ~20-25% of subjects on IFNβ treatment. These antibodies neutralise the effects of interferon beta, hence the drug loses its effect. In several countries testing for NABs is part of routine clinical practice."

"The one issue that was not discussed is the long-term implications of having NABs. IFNβ is a single gene product and is therefore the only protein in its class and has several unique biological functions in relation to the immune system and the health of bone; it inhibits the cell called the osteoclast that is responsible for the breaking down or remodelling of bone."

"The question is will MS'ers with persistent high levels of NABs, that presumably neutralise natural IFNβ within the body, develop long-term immunological problems; possibly secondary malignancies, rare infections or autoimmunity?"
Secondary cancer
"Will NABs predispose to the development of osteoporosis (thinning of bones)?"
Osteopaenia or osteoporosis
"MS is a disease of young woman; will the active transport of NABs into the foetal circulation via the placenta have any deleterious effects on the developing immune system or skeleton of the unborn child?" 
Foetal-placental unit
"To the best of my knowledge these questions have not been systematically studied. These potential long-term effects of NABs may be subtle therefore we need to remain vigilant to the possibility that NABs may have negative effects." 

"If you have been on IFNβ, and have been shown to have NABs, and have any problems or concerns please discuss them with your neurologist or nurse specialist."

"The following article addresses the issue of the persistence of NABs. Persistence seems to be a big problem with IFNβ-1a (Rebif and Avonex) and less of a problem with IFNβ-1b (Betaseron, Betaferon or Extavia). However, NABs to IFNβ-1b only disappear if the IFNβ-1b is continued long-term." 


OBJECTIVE: The main objective was to follow serum levels of neutralizing antibodies (NABs) against interferon-beta (IFNbeta) after discontinuation of IFNbeta therapy.


BACKGROUND: A large proportion of patients treated with recombinant IFNbeta for MS develop therapy-induced NABs. Knowledge of persistence of NABs after discontinuation of therapy is limited. 
Design/patients: A retrospective follow-up study of patients treated in Denmark for RRMS with IFNbeta for at least 12 months. NAB-positive patients, who discontinued therapy, were followed up with measurements of NABs.

RESULTS:  Thirty-seven patients were included. Mean follow-up time was 22 months. Of the 29 patients with a NAB titre at or above 25 prior to termination of therapy, only three patients reverted to a titre below 25. Of these, two had a titre below 200 and one patient a titre of 600 at the last examination before treatment stop. The longest post-treatment follow-up during which a patient maintained NAB positivity was 59 months.

CONCLUSION: NABs against IFNbeta, especially with high titres, tend to persist after discontinuation of IFNbeta therapy. NABs should always be measured before reinstitution of IFNbeta treatment in NAB-positive patients.

"Because of our concerns regarding the persistence of NABs we are currently recruiting for a clinical trial to try and trick the immune system into stopping the production of NABs. This is an exploratory study and if successful will have major implications for the field of immunology. For example the method we are using may be suitable for use in solid organ transplantation."

1 comment:

  1. Re "The question is will MS'ers with persistent high levels of NABs, that presumably neutralise natural IFNβ within the body, develop long-term immunological problems ... ":
    -Are NABs the same for all interferon betas? (IFNb-1a, IFNb-1b, natural IFNb)
    -Isn't it possible to check whether NABs are really working against natural IFNb?
    -If long-term problems are possible then many MS'ers will have them already. Have such problems been reported? (even if there is no systematic study)

    Re "The longest post-treatment follow-up during which a patient maintained NAB positivity was 59 months.":
    -Does that mean any immunological problems because of NABs will go away within 5 years of stopping interferon treatment?

    Re "If you have been on IFNβ, and have been shown to have NABs, and have any problems or concerns please discuss them with your neurologist or nurse specialist.":
    -Will they be interested in anything other than whether the treatment works/needs to be changed?

    ReplyDelete

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