IHS Global Insight Perspective | |
Significance | The United Kingdom's National Institute for Health and Clinical Excellence (NICE) has recommended MabThera/Rituxan (rituximab) for the treatment of rheumatoid arthritis (RA) patients in which disease-modifying antirheumatic drugs or at least one tumour necrosis factor inhibitor have been inadequate. Enbrel (etanercept), Remicade (infliximab), Orencia (abatacept), and Humira (adalimumab) have also secured positive recommendations, but only in patients who cannot be treated with MabThera. |
Implications | MabThera is the clear winner in this final guidance. The guidance on the other drugs is a departure from NICE's preliminary guidance, which indicated that Enbrel, Remicade, and Humira should only be used in the appraised indication for research purposes, whereas Orencia was rejected outright for a second time. |
Outlook | Given that up to 30% of RA patients may need to switch from one treatment regime to another over the course of their treatment, MabThera is now in a good position to capture this share of the market. Although the manufacturers of the other four drugs are not expected to gain much from this guidance, the fact that their drugs have been recommended with fewer restrictions than advised by NICE in preliminary consultations will come as a relief. |
The U.K. National Institute for Health and Clinical Excellence (NICE) has published final guidance documents for five rheumatoid arthritis (RA) drugs—Enbrel (etanercept; Wyeth/Pfizer, U.S.), Remicade (infliximab; Johnson & Johnson/Schering-Plough, U.S.), Humira (adalimumab; Abbott, U.S.), MabThera/Rituxan (rituximab; Roche, Switzerland), and U.S. firm Bristol-Myers Squibb's (BMS's) Orencia (abatacept)—looking specifically at the use of these drugs after the failure of a tumour necrosis factor (TNF) inhibitor. According to the guidance, MabThera in combination with methotrexate (MTX) is recommended for use in patients for whom disease-modifying antirheumatic drugs (DMARDs) or at least one TNF inhibitor have been inadequate, or in patients who are intolerant of DMARDs. In addition, treatment should only be continued in patients who respond adequately to initial therapy, with treatment intervals after every six months. Treatment with Enbrel, Remicade, and Humira is only recommended in patients for whom treatment with DMARDs—including at least one TNF inhibitor—has been inadequate, but who cannot be treated with MabThera plus MTX due to contraindication to methotrexate, or when methotrexate is withdrawn due to an adverse event. As in the case of MabThera, NICE has said that treatment should be continued only if there is an adequate response after six months.
The Five RA Drugs at a Glance | |||
Drug | Manufacturer | U.K. Indication | Annual Cost of Treatment |
Humira | Abbott | Treatment of moderate-to-severe, active RA in adult patients for whom response to DMARDs—including MTX—has been inadequate, or for patients not previously treated with MTX. | £9,295 for 26 doses |
Enbrel | Pfizer/Wyeth | Treatment of moderate-to-severe, active RA in adult patients for whom response to DMARDs—including MTX—has been inadequate, or for patients not previously treated with MTX. | £9,295 for 52 doses |
Remicade | Johnson & Johnson/Schering Plough | In combination with MTX for the treatment of active RA in adult patients for whom response to DMARDs—including MTX—has been inadequate, or for patients not previously treated with MTX or other DMARDs. | £7,553–8,812, depending on whether six or seven doses are needed |
MabThera | Roche | In combination with MTX for the treatment of severe active RA in adult patients for whom response to DMARDs—including one or more TNF inhibitor drugs—has been inadequate or unresponsive. | £3,492 per course of treatment |
Orencia | BMS | In combination with MTX for the treatment of severe, active RA in adult patients for whom response to DMARDs—including one or more TNF inhibitor drugs—has been inadequate or unresponsive. | £10,171.14 for the first year of treatment; £9,444.63 for subsequent years |
Source: NICE | |||
Cost Effectiveness
The manufacturers conducted cost-utility analyses for their respective drugs, using conventional DMARDs as the base-case comparator, with the exception of Enbrel, where a full model was not presented, and for Orencia, where the manufacturers used a different comparator.
Abbot's base-case incremental cost-effectiveness ratio (ICER) per quality-adjusted life year (QALY) gained for MabThera, Humira, Enbrel, Remicade, and Orencia in comparison with conventional DMARDs was estimated at £10,986 (US$16,903), £15,962, £15,962, £21,529, and £30,104, respectively. When it was assumed that treatment with MabThera would occur every six months, the ICERs per QALY gained for MabThera increased to £15,856. When Humira or Orencia were compared with MabThera given every six months, the ICERs stood at £16,280 per QALY gained. Humira or Enbrel compared with MabThera, given every 9 months, generated ICERs of £83,230 per QALY gained.
Pfizer used a Markov model to compare three treatment strategies: treatment with two sequential TNF inhibitors, treatment with a TNF inhibitor followed by a conventional DMARD, and treatment with a TNF inhibitor followed by MabThera. The ICER for TNF inhibitors compared with conventional DMARDs was between £14,501 and £15,294 per QALY gained. The ICER for TNF inhibitors compared with MabThera was between £16,225 and £19,077 per QALY gained
Schering-Plough used cost-utility analysis to compare the appraised RA drugs with conventional DMARDs. This analysis produced an ICER of £17,422–27,161 per QALY gained for MabThera, depending on the length of retreatment intervals. ICERs of £35,138, £35,898, £28,661, and £44,795 per QALY gained were generated respectively for Humira, Enbrel, Remicade, and Orencia compared with conventional DMARDs.
Roche performed a cost-utility analysis for MabThera compared with Humira, Enbrel, Remicade, and Orencia followed by treatment with conventional DMARDs. This analysis showed that MabThera was more effective and cheaper than Enbrel, Remicade, and Orencia. MabThera was shown to be less effective but less costly than Humira. When compared with conventional DMARDs, the ICER was £5,311 per QALY.
BMS's cost-utility analysis compared Orencia with MabThera, both followed by treatment with Remicade, as well as Orencia, compared with a basket of TNF inhibitors. The base-case analysis showed that when compared with a basket of TNF inhibitors, the ICER per QALY gained for Orencia was £23,019. When compared with MabThera, the ICER was £20,438 per QALY gained.
NICE also conducted its own economic analysis, using the Birmingham RA model to undertake a comparison of the drugs with each other, as well as a comparison of each drug with conventional DMARDs. This yielded an ICER per QALY of £34,300 for Humira, £38,900 for Enbrel, and £36,100 for Remicade. The ICER per QALY gained for Orencia in comparison with DMARDs was estimated at £38,400. When compared with Humira, Enbrel, and Remicade, the ICERs per QALY for Orencia were £46,400, £37,800, and £41,700, respectively. The analysis for MabThera in comparison with DMARDs yielded an ICER per QALY of £21,100; however, MabThera dominated TNF-inhibitors.
Outlook and Implications
MabThera has still emerged as the big winner in this guidance, as NICE has essentially recommended that it is the most cost-effective RA drug for treatment after the failure of a TNF inhibitor. In the preliminary consultations for the other four drugs, NICE said that Humira, Enbrel, and Remicade should only be used on a research basis in the evaluated setting, while Orencia had been hit by a number of negative opinions. NICE has certainly softened its tone towards the drugs, as they can now be used where treatment with MabThera is not appropriate. With up to 30% of patients switching from one RA drug to another over the course of their treatment, this guidance should certainly translate into gains for these companies, especially in the case of MabThera. NICE has recently softened its heavy-handed approach to RA drugs. Earlier this year, another TNF inhibitor, Cimzia (certolizumab pegol; UCB; Belgium), was also recommended for use, followed by positive guidance for another Roche RA drug, RoActemra/Actemra (tocilizumab), despite initial rejections for both of these drugs. The full guidance is available here.