NICE Issues Final Guidance for RA Drugs

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but who cannot be treated with MabThera plus MTX due to contraindication to methotrexate, or when methotrexate is withdrawn due to an adverse event.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.

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