Switching

Switching-2-interferon-beta

Last updated on February 22nd, 2023 at 06:13 pm

Possible reasons to switch

  • In general, interferon-beta (IFN-beta) is not immunosuppressive.
  • Monitoring requirements are not too onerous.
  • A failure to respond to other DMTs does not necessarily predict a lack of response to IFN-beta.
  • Pregnancy: IFN-beta has been shown to be safe in pregnancy.

Reasons for caution

  • IFN-beta formulations are generally poorly tolerated long-term, owing to injection site reactions and flu-like side effects, often resulting in low adherence.
  • Their efficacy in preventing brain volume loss and damage to nerve fibres is modest.
  • IFN-beta formulations can (to varying degrees) induce neutralising antibodies (NABs). The resulting anti-IFN-beta NABs may potentially cross the placenta and affect foetal development.
  • There is small increased risk of spontaneous abortion when falling pregnant while on IFN-beta treatment.

IFN-beta to IFN-beta switch

The only reason to switch between IFN-beta preparations is for local, or systemic, intolerance. Many patients with local skin, or injection site, reactions move to intramuscular IFN-beta-1a (Avonex), which does not cause local skin reactions. In contrast, many patients move from IFN-beta-1a (Avonex) to IFN-beta-1a (Rebif) or -1b (Betaferon) because of persistent flu-like reactions. Because Avonex allows the interferon receptors to regenerate before the next injections, mild flu-like symptoms can persist; this does not happen with Rebif and Betaferon. Betaferon is administered on alternate days; however, Rebif is given three times per week, and some patients experience mild flu-like side effects after the 2-day injection break (once each week) but not after a 1-day break (twice each week).

NABs

If you have developed NABs to one IFN-beta preparation these cross-react with the other preparations. In this situation NABs would simply neutralise the effect of a new IFN-beta formulation.

Lack of efficacy

I would not recommend switching between IFN-beta preparations because of lack of efficacy or perceived lack of efficacy. If you have had a suboptimal response to one IFN-beta preparation, it will make sense to switch classes. I generally tend to escalate treatment to a more efficacious DMT rather than switch to another moderate efficacy DMT: vertical escalation rather than horizontal switching.

Other DMTs

Provided the baseline screening blood tests are fine and there are no specific contraindications, I see no reason why IFN-beta can’t be used after any of the other licensed DMTs. Apart from NAbs inhibiting the action of other IFN-beta formulations, I am not aware that a failure to respond to a different DMT predicts a lack of response to another IFN-beta. However, if you are switching due to a suboptimal response, I would recommend a potentially more efficacious DMT. There is reasonable real-life data that shows switching upwards (escalation) gives a better overall response rate than switching to a similar efficacy DMT (horizontal switching).

Special circumstances

The presence of some specific comorbidities or adverse events may make it difficult to switch from one DMT to IFN-beta. For example, a persistent low lymphocyte count (<800), low neutrophil count (<1,000), low total white cell count (<1,500) and/or abnormal LFTs, that can occur with several DMTs, are relative contraindications to IFN-beta. Similarly, the presence of a monoclonal gammopathy (abnormal protein in the blood) is a contraindication to IFN-beta due to the risk of capillary leak syndrome (fluid on the lungs).