RRMS-HDA (High Disease Activity)
Six European clinical neurologists met in December 2015 to finish and validate a model initially constructed by Merck KGaA staff of the benefit-safety balance of six RRMS drugs. After completing the RRMS model, the clinicians replaced some of the original data to reflect research outcomes for patients experiencing High Disease Activity, with results reported here. Click here to open the original RRMS model in a new window for comparing the two sets of results.
The six drugs are listed here, with figures that represent the benefit-safety balance of each. Green figures indicate the best benefit-safety balance; Red the worst. For HDA, cladribine shows the best benefit-safety balance.
The six drugs are listed here, with figures that represent the benefit-safety balance of each. Green figures indicate the best benefit-safety balance; Red the worst. For HDA, cladribine shows the best benefit-safety balance.
- Cladribine 76
- Alemtuzumab 62
- Natalizumab 61
- Dimethyl fumarate 60
- Fingolimod 49
- Teriflunomide 47
The numbers are preference values out of 100, which take into account available data for the effects and judgements by the experts about the clinical relevance of the effects. They do not take account of contra-indications, interactions with other drugs, or any precautions.
Reductions in the frequency of MS symptoms define each drug's favourable effects, and frequencies of side effects are classed as unfavourable effects. The breakdown of the preference values into those two categories is shown in the following table. The weighted sum of the two figures for each drug gives its overall benefit-safety balance.
Bar graphs after the 51-49 weight is applied show the separate contribution of benefits and safety to the total. Note, for example, that cladribine is second best for both benefits and safety, but together they combine to move the benefit-safety balance well above the rest.
Another way to look at the benefit and safety information is to show each drug's two figures from the above table (before the benefit-safety trade-off is considered) in a 2-D plot.
This figure facilitates comparisons of the drugs. The top rating of cladribine is close to being best for both benefits and safety; it is the best drug over a wide range of trade-off weights. Also, cladribine is better in both benefits and safety than 3 and 5, and 4 is better in both than 5.
All the above is based on (1) the following data, based on available public sources, and (2) experts' judgements about the clinical relevance of the data. To support patient-oriented prescribing based on the evidence, green shading identifies the best drug for each favourable effect while red shows the worst drug for each unfavourable effect.
* (1) oral vs iv, (2) few or many doses, (3) monitoring during administration (Y or N) and (4) Co-administration of other drugs (Y or N). Bold Face means preferred.
AR=adverse reaction; AV=atrioventricular; EDSS=expanded disability status scale; Gd+=gadolinium enhanced; PML=progressive multifocal leukoencephalopathy.
AR=adverse reaction; AV=atrioventricular; EDSS=expanded disability status scale; Gd+=gadolinium enhanced; PML=progressive multifocal leukoencephalopathy.
Reference: Vermersch, P., Martinelli, V., Pfleger, C., Rieckmann, P., Alonso-Magdalena, L., Galazka, A., . . . Phillips, L. (2019). Benefit-risk Assessment of Cladribine using Multi-Criteria Decision Analysis (MCDA) for Patients with Relapsing-Remitting Multiple Sclerosis. Clinical Therapeutics, 41(2), 249-260.