Estimated impact for the NHS | Skin involvement in systemic sclerosis: rituximab | Advice

Other medicines

The British Society for Rheumatology (BSR) and British Health Professionals in Rheumatology (BHPR) guideline for treating systemic sclerosis advises that skin involvement in diffuse systemic sclerosis may be treated with either methotrexate or mycophenolate. Other options include cyclophosphamide, oral corticosteroid therapy and possibly rituximab. Azathioprine or mycophenolate should be considered after cyclophosphamide to maintain improvement in skin sclerosis and/or lung function. Use of any of these immunosuppressants would be off‑label.

Costs of other medicines

No cost-effectiveness studies of rituximab for treating scleroderma were identified.

Table 3 shows the cost of rituximab alongside the costs of other immunosuppressants that are used for diffuse systemic sclerosis; however, these costs are not directly comparable for many reasons. Although the BSR/BHPR guideline advises which immunosuppressants may be considered, they do not make any recommendations around dosage or duration. Dosages for rituximab included in the table are those commonly used in the studies: dosages for other immunosuppressants are based on the summaries of product characteristics for other indications and expert opinion. The doses shown do not represent the full range that can be used and they do not imply therapeutic equivalence. Note that, in the studies, rituximab was used in addition to other, conventional immunosuppressants, not instead of these medicines.

The costs shown in the table are for the medicines only (excluding VAT) and do not include any local procurement discounts or other costs incurred, such as dilution and administration, standard supportive therapy, or attendance for day case treatment. They also assume that vials are used for only 1 patient and are not shared between patients. Standard supportive therapy for rituximab includes premedication with paracetamol, an antihistamine and methylprednisolone.

Table 3 Costs of rituximab compared with other immunosuppressants

Medicine	Usual dose ^a	Estimated annual cost excluding VAT
Rituximab (intravenous)	375 mg/m² weekly for 4 weeks at baseline and 6 months	£9,779.20^b,c
Rituximab (intravenous)	1,000 mg at 0 and 2 weeks	£3,492.60^c,d
Methotrexate (oral)	15 mg weekly	£19.72^e
Cyclophosphamide (intravenous)	15 mg/kg monthly	£204.72^f
Cyclophosphamide (oral)	2 mg/kg daily	£1,522.05^g
Mycophenolate mofetil (oral)	1,000 mg twice daily	£180.16^h
Mycophenolate sodium (oral)	720 mg twice daily	£2,353.40^c
Azathioprine (oral)	2.5 mg/kg daily	£64.85ⁱ
^a Dosages for rituximab are those commonly used in the studies. Dosages for other medicines are based on the summaries of product characteristics for other indications and expert opinion. None of these medicines are licensed for scleroderma and use would be off-label. The doses shown do not represent the full range that can be used and they do not imply therapeutic equivalence ^b Based on a dose of 700 mg for an adult with a body surface area of 1.86 m² given 1×50 ml and 2×10 ml vials for each dose ^c Cost taken from MIMS, January 2017 ^d Assuming no further treatment cycles; some participants in the studies received more than 1 cycle of treatment ^e Cost taken from the Drug Tariff, January 2017 ^f Cost taken from the British national formulary (BNF), January 2017; based on a 70 kg adult given 1×1 g vial monthly ^g Cost taken from the Drug Tariff, January 2017; based on a 70 kg adult given 3×50 mg tablets daily ^h Cost taken from the Drug Tariff, January 2017; based on 500 mg tablets: 250 mg capsules would be substantially more expensive at £2,401.99 ⁱ Costs taken from the Drug Tariff, January 2017; based on a 70 kg adult given 1×25 mg and 3×50 mg tablets daily

Current or estimated usage

Estimating current usage of rituximab for treating scleroderma is difficult because rituximab is used to treat various conditions. No information on prescribing rituximab for scleroderma was available at the time this evidence summary was prepared.

Likely place in therapy

Local decision makers need to take safety, efficacy, cost and patient factors into account when considering the likely place in therapy of rituximab for systemic sclerosis.

The BSR/BHPR guideline for treating systemic sclerosis suggests that methotrexate and mycophenolate are the preferred options for treating skin involvement in diffuse systemic sclerosis. Cyclophosphamide and oral corticosteroid therapy (in as low a dose as possible to suppress symptoms, and with close monitoring of renal function) are other options, and rituximab is listed as a possible option. Although the studies included in this evidence summary suggest that rituximab may be effective for treating skin involvement in some people with diffuse systemic sclerosis, the evidence is of low quality and has many limitations, and it is difficult to draw any firm conclusions from it.

The adverse effects seen in the studies reflect those listed in the summary of product characteristics for rituximab. Several deaths and hospitalisations were reported with rituximab (and usual care): not all were considered related to the study medication.

The acquisition cost of rituximab is more than that of other medicines that are used for diffuse systemic sclerosis. However, many factors need taking into account. In the studies, rituximab was often taken in addition to other immunosuppressants.

Specialists involved in producing this evidence summary considered that rituximab is currently only an option for treating skin involvement in diffuse systemic sclerosis that is progressing despite an adequate trial of standard immunosuppressant treatment (or when standard immunosuppressant treatment cannot be tolerated) in limited situations. For example, when autologous hematopoietic stem cell transplantation is contraindicated, or when cyclophosphamide is not suitable because of the risk of sterility and there are no other options. The risk of serious adverse effects with rituximab should be taken into account.