1 Recommendations

This guidance only includes recommendations for treating severe rheumatoid arthritis.

The scope for this technology appraisal also included moderate rheumatoid arthritis. This is covered by NICE technology appraisal guidance on upadacitinib for treating moderate rheumatoid arthritis.

1.1 Upadacitinib, with methotrexate, is recommended as an option for treating active rheumatoid arthritis in adults whose disease has responded inadequately to intensive therapy with a combination of conventional disease-modifying antirheumatic drugs (DMARDs), only if:

disease is severe (a disease activity score [DAS28] of more than 5.1) and
the company provides upadacitinib according to the commercial arrangement.

1.2 Upadacitinib, with methotrexate, is recommended as an option for treating active rheumatoid arthritis in adults whose disease has responded inadequately to or who cannot have other DMARDs, including at least 1 biological DMARD, only if:

disease is severe (a DAS28 of more than 5.1) and
they cannot have rituximab and
the company provides upadacitinib according to the commercial arrangement.

1.3 Upadacitinib, with methotrexate, is recommended as an option for treating active rheumatoid arthritis in adults whose disease has responded inadequately to rituximab and at least 1 biological DMARD, only if:

disease is severe (a DAS28 of more than 5.1) and
the company provides upadacitinib according to the commercial arrangement.

1.4 Upadacitinib can be used as monotherapy for people who cannot take methotrexate because it is contraindicated or because of intolerance, when the criteria in sections 1.1, 1.2 or 1.3 are met.

1.5 Continue treatment only if there is a moderate response measured using European League Against Rheumatism (EULAR) criteria at 6 months after starting therapy. After an initial response within 6 months, stop treatment if at least a moderate EULAR response is not maintained.

1.6 When using the DAS28, healthcare professionals should take into account any physical, psychological, sensory or learning disabilities, or communication difficulties that could affect the responses to the DAS28 and make any adjustments they consider appropriate.

1.7 These recommendations are not intended to affect treatment with upadacitinib that was started in the NHS before this guidance was published. People having treatment outside these recommendations may continue without change to the funding arrangements in place for them before this guidance was published, until they and their NHS clinician consider it appropriate to stop.

Why the committee made these recommendations

Clinical trials show that upadacitinib with methotrexate or conventional DMARDs is more effective than methotrexate or conventional DMARDs for treating moderate to severe active rheumatoid arthritis that has not responded adequately to conventional DMARDs. The trials also show that for moderate to severe active rheumatoid arthritis that has not responded adequately to conventional DMARDs, upadacitinib with methotrexate is more effective than adalimumab with methotrexate or placebo with methotrexate.

Because there are no trials comparing upadacitinib with the full range of biological DMARDs, the company did an indirect comparison. This shows that upadacitinib with conventional DMARDs (including methotrexate) or on its own works as well as the biological DMARDs that NICE has already recommended.

Based on the health-related benefits and costs compared with conventional and biological DMARDs, upadacitinib alone, or with methotrexate, is recommended only for severe active rheumatoid arthritis, in line with recommendations in NICE's technology appraisal guidance on: