Drugs used not listed here:

• Azathioprine, Ciclosporin, Mycophenolate, Abrocitinib and Secukinumab see section 8.2.1 Immunosuppressive agents
  • Azathioprine: treatment of adults with severe rheumatoid arthritis, systemic lupus erythematosus and other rheumatological diseases.
  • Mycophenolate: treatment of adults with autoimmune disease
  • Ciclosporin: treatment of adults with severe active rheumatoid arthritis
• Methotrexate, for preparations see section 8.4.3 Antifolates
  • Treatment of adults with inflammatory joint disease and autoimmune disease
• Sulfasalazine, see section 1.5.1 Aminosalicylates
• Cyclophosphamide, see section 8.1.1 Alkylating drugs
• Guselkumab and Ixekizumab, see section 13.5.3 Drugs affecting the immune response
• Rituximab, see section 8.5.8 Monoclonal antibodies

Disease-Modifying Anti-Rheumatic Drugs (DMARDs)

Hydroxychloroquine

• Tablets 200mg (£3.29 = 200mg 12 hourly)

Indications

• Rheumatoid arthritis
• Discoid and systemic lupus erythematosus
• Connective tissue disease (off-label)
• Dermatological conditions caused or aggravated by sunlight

Dose

• Up to 400mg per day. Dose should not exceed 6.5 mg/kg/day (calculated from ideal body weight)

Notes

1. Treatment will be initiated and supervised by a rheumatologist or dermatologist with expertise in treating the indications listed above; the specialist will establish the patient on a stable dose of hydroxychloroquine prior to asking the GP to take on long-term prescribing.
   
2. The specialist will continue to oversee the ongoing management of the condition being treated with hydroxychloroquine (including periodic review of disease response and ongoing need for treatment).
3. If there are any changes in the severity of the patient's condition or concomitant medication, or if troublesome adverse reactions develop, the GP should seek advice from the specialist.
4. NHS Devon ICB has commissioned a hydroxychloroquine retinopathy monitoring service. In accordance with the service specification:
   1. The specialist will refer new patients to the monitoring service at the start of treatment or at the start of care with that provider if the patient has moved into the area.
   2. The specialist will identify any existing patients who are receiving hydroxychloroquine and are not known to the monitoring service.
   3. The monitoring service will manage a recall system for future appointments once a patient has been seen by them.
   4. If a patient reports a visual disturbance (e.g. blurred vision, changes in visual acuity or abnormal colour vision) before their next retinopathy monitoring appointment, redirect to high street optician or refer to ophthalmology for assessment as appropriate.
5. See Hydroxychloroquine/Chloroquine Retinopathy Monitoring Service Key Message for further information.
6. MHRA Drug Safety Update (February 2022): Hydroxychloroquine, chloroquine: increased risk of cardiovascular events when used with macrolide antibiotics; reminder of psychiatric reactions
   1. An observational study has shown that co-administration of azithromycin with hydroxychloroquine in patients with rheumatoid arthritis is associated with an increased risk of cardiovascular events (including angina or chest pain and heart failure) and cardiovascular mortality.
   2. Carefully consider the benefits and risks before prescribing systemic azithromycin or other systemic macrolide antibiotics (erythromycin or clarithromycin) to patients being treated with hydroxychloroquine or chloroquine.
   3. Be vigilant for psychiatric reactions associated with hydroxychloroquine or chloroquine, especially in the first month of treatment; events have been reported in patients with no prior history of psychiatric disorders.
   4. See the safety update for advice to give to patients.

Leflunomide

• Tablets 10mg, 20mg (£2.44 = 20mg daily)

Indications

• Active rheumatoid arthritis
• Active psoriatic arthritis

Notes

1. West Devon: refer to individual shared care guidelines for use in Rheumatology and Dermatology conditions.
2. South Devon: refer to individual shared care guidelines for use in Rheumatology.

Penicillamine

• Tablets 125mg, 250mg

Phosphodiesterase Type-4 inhibitors

Apremilast

• Tablets 10mg, 20mg, 30mg

Notes

1. For use in line with NICE TA419 Apremilast recommended for treating moderate to severe plaque psoriasis (November 2016).
2. For use in line with NICE TA433 Apremilast for treating active psoriatic arthritis (February 2017).

Janus kinase (JAK) inhibitors

Baricitinib

• Tablets 2mg, 4mg

Notes

1. An interim UK clinical commissioning policy has been issued to define routine access to baricitinib for the treatment of COVID-19:
   1. Baricitinib is recommended as a treatment option for adults and children (aged two years and over) hospitalised due to COVID-19 in accordance with the criteria set out in the interim policy (28 November 2022) and clinical guide (CEM/CMO/2022/017).
   2. Information on dose and administration is included in the policy.
   3. Baricitinib is contraindicated during pregnancy. Women of childbearing potential have to use effective contraception during and for at least 1 week after treatment. Clinicians are advised to refer to the Summary of Product Characteristics for baricitinib for more information on use during pregnancy or lactation.
   4. Information on use with other routine treatments for COVID-19 is included in the policy.
   5. Pre-authorised use of baricitinib for individual patients with COVID-19 is required using Blueteq (CEM/CMO/2022/017).
   6. Use of baricitinib for the treatment of COVID-19 is off-label. Seek advice from the Torbay and South Devon trust pharmacy department or the University Hospitals Plymouth trust pharmacy department on whether approval has been given for use in COVID-19 before prescribing baricitinib for this indication.
   7. For information on recording the use of baricitinib in discharge letters to primary care, see CEM/CMO/2022/017.
2. NICE TA466: Baricitinib (Olumiant) is recommended as an option for treating active rheumatoid arthritis in adults (August 2017):
   1. with methotrexate, in those whose disease has responded inadequately to intensive therapy with a combination of conventional disease-modifying antirheumatic drugs (DMARDs), only when the criteria of the NICE TA are met.
   2. with methotrexate, in those whose disease has responded inadequately to or who cannot have other DMARDs, including at least 1 biological DMARD, only when the criteria of the NICE TA are met.
   3. as monotherapy for those who cannot take methotrexate because it is contraindicated or because of intolerance, only when the criteria of the NICE TA are met.
   4. 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, withdraw treatment if at least a moderate EULAR response is not maintained.
3. NICE TA681: Baricitinib (Olumiant) is recommended as an option for treating moderate to severe atopic dermatitis in adults (March 2021), only if:
   1. the disease has not responded to at least 1 systemic immunosuppressant, such as ciclosporin, methotrexate, azathioprine and mycophenolate mofetil, or these are not suitable, and
   2. the company provides it according to the commercial arrangement.
   3. Assess response from 8 weeks and stop baricitinib if there has not been an adequate response at 16 weeks, as defined in the NICE TA.
4. NICE TA926: Baricitinib (Olumiant) is not recommended, within its marketing authorisation, for treating severe alopecia areata in adults (October 2023).
5. MHRA Drug Safety Update (March 2020): Baricitinib (Olumiant): risk of venous thromboembolism
   1. Use caution if considering baricitinib in patients with additional risk factors for deep vein thrombosis and pulmonary embolism, such as prior medical history of venous thromboembolism, surgery, immobilisation, older age, and obesity.
   2. Discontinue baricitinib treatment permanently if clinical features of venous thromboembolism occur.
   3. Advise patients undergoing treatment with baricitinib to seek urgent medical attention if they experience a painful swollen leg, chest pain, or shortness of breath.
6. MHRA Drug Safety Update (August 2020): Baricitinib (Olumiant): increased risk of diverticulitis, particularly in patients with risk factors
   1. Cases of diverticulitis and gastrointestinal perforation have been reported in patients taking baricitinib.
   2. Use caution in patients with pre-existing diverticular disease and in patients on longterm concomitant medications associated with an increased risk of diverticulitis such as non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and opioids.
   3. Advise patients on baricitinib to seek immediate medical care if they experience severe abdominal pain especially accompanied with fever, nausea and vomiting or other symptoms of diverticulitis.
   4. Ensure prompt evaluation of any patients on baricitinib who present with new-onset abdominal signs and symptoms to identify early diverticulitis or gastrointestinal perforation.

Deucravacitinib

• Tablets 6mg

Notes

1. NICE TA907: Deucravacitinib (Sotyktu) is recommended as an option for treating moderate to severe plaque psoriasis in adults, only if; the Psoriasis Area and Severity Index (PASI) score is 10 or more and the Dermatology Life Quality Index (DLQI) score is more than 10; the condition has not responded to other systemic treatments, including ciclosporin, methotrexate and phototherapy, or there option are contraindicated or not tolerated; and the company provides it according to the commercial arrangement (June 2023).
   1. Consider stopping deucravacitinib between 16 weeks and 24 weeks if there has not been at least a 50% reduction in the PASI score (PASI 50) from when treatment started.
   2. Consider stopping deucravacitinib at 24 weeks if the psoriasis has not responded adequately (see TA for adequate response definitions).
   3. If people with the condition and their clinicians consider deucravacitinib to be 1 of a range of suitable treatments (see section 3.18), after discussing the advantages and disadvantages of all the options, use the least expensive.
   4. Take into account how skin colour could affect the PASI score and make any adjustments needed.
   5. Take into account any physical, sensory or learning disabilities, or communication difficulties that could affect the responses to the DLQI and make any adjustments needed.

Filgotinib

• Tablets 100mg, 200mg

Notes

1. NICE TA676: Filgotinib for treating moderate to severe rheumatoid arthritis (February 2021):
   1. Filgotinib (Jyseleca), with methotrexate, is recommended as an option for treating active rheumatoid arthritis in adults whose disease has responded inadequately to intensive therapy with 2 or more conventional disease-modifying antirheumatic drugs (DMARDs), only if:
      • disease is moderate or severe (a disease activity score [DAS28] of 3.2 or more) and
      • the company provides filgotinib according to the commercial arrangement.
   2. Filgotinib (Jyseleca), 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 filgotinib according to the commercial arrangement.
   3. Filgotinib (Jyseleca), 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 filgotinib according to the commercial arrangement.
   4. Filgotinib can be used as monotherapy when methotrexate is contraindicated or if people cannot tolerate it, when the criteria in note 1a, 1b or 1c are met.
   5. If more than 1 treatment is suitable, start treatment with the least expensive drug (taking into account administration costs, dose needed and product price per dose).
   6. Continue treatment only if there is a moderate response measured using European League Against Rheumatism (EULAR) criteria at 6 months after starting therapy. If this initial response is not maintained at 6 months, stop treatment.
   7. 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.
2. NICE TA792: Filgotinib (Jyseleca) is recommended, within its marketing authorisation, as an option for treating moderately to severely active ulcerative colitis in adults (June 2022):
   1. when conventional or biological treatment cannot be tolerated, or
   2. if the disease has not responded well enough or has stopped responding to these treatments, and
   3. if the company provides filgotinib according to the commercial arrangement.

Momelotinib

• Tablets 100mg, 150mg, 200mg

Notes

1. NICE TA957: Momelotinib (Omjjara) is recommended as an option for treating myelofibrosis-related splenomegaly of symptoms in adults with moderate to severe anaemia who have not had a JAK inhibitor or have had ruxolitinib (March 2024), only if:
1. they have intermediate-2 or high-risk myelofibrosis, and
2. the company provides it according to the commercial arrangement.

Ritlecitinib

• Capsules 50mg

Notes

1. NICE TA958: Ritlectinib (Litfulo) is recommended, within its marketing authorisation, as an option for treating severe alopecia areata in people 12 years and over, only if the company provides it according to the commercial arrangement (March 2024).

Tofacitinib

• Tablets 5mg, 10mg

Notes

1. NICE TA480: Tofacitnib for moderate to severe rheumatoid arthritis (October 2017):
   1. Tofacitnib (Xeljanz), 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 anti-rheumatic drugs (DMARDs), only when the criteria of the NICE TA are met.
   2. Tofacitinib (Xeljanz), 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 when the criteria of the NICE TA are met.
   3. Tofacitinib can be used as monotherapy for adults who cannot take methotrexate because it is contraindicated or because of intolerance, when the criteria in of the NICE TA are met.
2. NICE TA543: Tofacitnib (Xeljanz), with methotrexate, is recommended as an option for treating active psoriatic arthritis in adults, only when the criteria of the NICE TA are met (October 2018).
3. NICE TA547: Tofacitinib (Xeljanz) is recommended as an option for treating moderately to severely active ulcerative colitis in adults when conventional therapy or a biological agent cannot be tolerated or the disease has responded inadequately or lost response to treatment (November 2018).
4. NICE TA735: Tofacitinib (Xeljanz) is recommended as an option for treating active polyarticular juvenile idiopathic arthritis (JIA; rheumatoid factor positive or negative polyarthritis and extended oligoarthritis), and juvenile psoriatic arthritis in people 2 years and older. This is if their condition has responded inadequately to previous treatment with disease-modifying antirheumatic drugs (DMARDs) (October 2021), and only if:
   1. a tumour necrosis factor (TNF) alpha inhibitor is not suitable or does not control the condition well enough, and
   2. the company provides tofacitinib according to the commercial arrangement.
   3. Tofacitinib can be used with methotrexate, or as monotherapy when methotrexate is not tolerated or if continued treatment with methotrexate is inappropriate.
5. NICE TA920: Tofacitinib (Xeljanz) is recommended as an option for treating active ankylosing spondylitis that is not controlled well enough with conventional therapy in adults (October 2023), only if:
   1. tumour necrosis factor (TNF)-alpha inhibitors are not suitable or do not control the condition well enough and
   2. the company provides it according to the commercial arrangement.
   3. Refer to TA920 for treatment continuation criteria and other considerations.
6. MHRA Drug Safety Update (March 2020): Tofacitinib (Xeljanz): new measures to minimise risk of venous thromboembolism and of serious and fatal infections
   1. Tofacitinib is associated with a dose-dependent increased risk of serious venous thromboembolism.
   2. Use caution in any patients with known risk factors for venous thromboembolism in addition to the underlying disease (see MHRA October 2021 below for risk factors for other adverse events associated with tofacitinib which should be taken into account in deciding whether treatment with tofacitinib is appropriate).
   3. In patients with ulcerative colitis who have known risk factors for venous thromboembolism in addition to the underlying disease, use of 10mg twice daily tofacitinib for maintenance treatment is not recommended unless no suitable alternative treatment is available.
   4. Do not exceed the recommended dose of 5mg twice daily for rheumatoid arthritis or 5mg twice daily for psoriatic arthritis in any patients.
   5. Inform patients of the signs and symptoms of venous thromboembolism before they start tofacitinib and advise them to seek prompt medical help if they develop signs such as a painful swollen leg, chest pain, or shortness of breath.
   6. Discontinue tofacitinib treatment permanently if signs of venous thromboembolism occur.
   7. Patients older than 65 years of age are at an increased risk of serious infections and should be treated with tofacitinib only if there is no alternative treatment (see MHRA October 2021 below for risk factors for other adverse events associated with tofacitinib in patients older than 65 years which should be taken into account in deciding whether treatment with tofacitinib is appropriate).
7. MHRA Drug Safety Update (October 2021): Tofacitinib (Xeljanz): new measures to minimise risk of major adverse cardiovascular events and malignancies
   1. A clinical safety trial in patients with rheumatoid arthritis aged 50 years or older with at least one cardiovascular risk factor found that compared with TNF-alpha inhibitors (etanercept or adalimumab), tofacitinib was associated with an increased risk of major adverse cardiovascular events and an increased risk of malignancies (excluding nonmelanoma skin cancer [NMSC]), particularly lung cancer and lymphoma).
   2. The following predictive risk factors were identified for:
      1. cardiovascular events: age older than 65 years, current or past smoking, history of diabetes, and history of coronary artery disease (including past myocardial infarction, coronary heart disease, stable angina pectoris, or coronary artery procedures)
      2. malignancy: age older than 65 years and current or past smoking.
   3. Only consider use of tofacitinib in patients with cardiovascular risk factors or malignancy risk factors (including current or previous history of malignancy other than successfully treated NMSC), irrespective of indication, if no suitable alternative treatment is available.
   4. For advice to give to patients and carers, see the safety update here.

Upadacitinib

• Modified-release tablets 15mg, 30mg, 45mg

Notes

1. NICE TA665: Upadacitinib for treating severe rheumatoid arthritis (December 2020):
   1. Upadacitinib (Rinvoq), 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.
   2. Upadacitinib (Rinvoq), 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.
   3. Upadacitinib (Rinvoq), 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.
   4. Upadacitinib can be used as monotherapy for people who cannot take methotrexate because it is contraindicated or because of intolerance, when the criteria of NICE TA665 are met.
   5. Refer to TA665 for continuation criteria and other considerations.
2. NICE TA744: Upadacitinib for treating moderate rheumatoid arthritis (November 2021):
   1. Upadacitinib (Rinvoq), with methotrexate, is recommended as an option for treating active rheumatoid arthritis in adults whose disease has responded inadequately to intensive therapy with 2 or more conventional disease modifying antirheumatic drugs (DMARDs), only if:
      • disease is moderate (a disease activity score [DAS28] of 3.2 to 5.1) and
      • the company provides upadacitinib according to the commercial arrangement.
   2. Upadacitinib can be used as monotherapy when methotrexate is contraindicated or if people cannot tolerate it, when the criteria of NICE TA744 are met.
   3. If more than 1 treatment is suitable, start treatment with the least expensive drug (taking into account administration costs, dose needed and product price per dose). This may vary because of differences in how the drugs are used and treatment schedules.
   4. Refer to TA744 for continuation criteria and other considerations.
3. NICE TA768: Upadacitinib for treating active psoriatic arthritis after inadequate response to DMARDs (February 2022):
   1. Upadacitinib (Rinvoq), alone or with methotrexate, is recommended as an option for treating active psoriatic arthritis in adults whose disease has not responded well enough to disease-modifying antirheumatic drugs (DMARDs) or who cannot tolerate them. It is recommended only if they have peripheral arthritis with 3 or more tender joints and 3 or more swollen joints and:
      • they have had 2 conventional DMARDs and at least 1 biological DMARD or
      • TNF-alpha inhibitors are contraindicated but would otherwise be considered (as described in NICE TA199: Etanercept, infliximab and adalimumab for the treatment of psoriatic arthritis).
   2. Upadacitinib is recommended only if the company provides it according to the commercial arrangement.
   3. Refer to TA768 for continuation criteria and other considerations.
4. NICE TA829: Upadacitinib for treating active ankylosing spondylitis
   1. Upadacitinib is recommended as an option for treating active ankylosing spondylitis that is not controlled well enough with conventional therapy in adults, only if:
      • tumour necrosis factor (TNF)-alpha inhibitors are not suitable or do not control the condition well enough and
      • the company provides upadacitinib according to the commercial arrangement.
   2. Refer to TA829 for continuation criteria and other considerations.
5. NICE TA814: Abrocitinib, tralokinumab or upadacitinib for treating moderate to severe atopic dermatitis (August 2022):
   1. Upadacitinib (Rinvoq) is recommended as an option for treating moderate to severe atopic dermatitis that is suitable for systemic treatment in adults and young people 12 years and over, only if:
      • the disease has not responded to at least 1 systemic immunosuppressant, or these are not suitable
      • the companies provide upadacitinib according to the commercial arrangement.
   2. Refer to TA814 for continuation criteria and other considerations.
6. NICE TA856: Upadacitinib (Rinvoq) is recommended, within its marketing authorisation, as an option for treating moderately to severe active ulcerative colitis in adults (January 2023):
   1. when conventional or biological treatment cannot be tolerated, or
   2. if the condition has not responded well enough or has stopped responding to these treatments, and
   3. if the company provides it according to the commercial arrangement.
7. NICE TA861: Upadacitinib (Rinvoq) is recommended as an option for treating active non-radiographic axial spondyloarthritis with objective signs of inflammation (shown by elevated C-reactive protein or MRI) that is not controlled well enough with non-steroidal anti-inflammatory drugs (NSAIDs) in adults (February 2023), only if:
   1. tumour necrosis factor (TNF)-alpha inhibitors are not suitable or do not control the condition well enough and
   2. the company provides it according to the commercial arrangement.
   3. Refer to TA861 for continuation criteria and other considerations.
8. NICE TA905: Upadacitinib (Rinvoq) is recommended as an option for treating moderately to severely active Crohn's disease in adults (June 2023), only if:
   1. the disease has not responded well enough or lost response to a previous biological treatment or
   2. a previous biological treatment was not tolerated or
   3. tumour necrosis factor (TNF)-alpha inhibitors are contraindicated and
   4. the company provides it according to the commercial arrangement.

T-Cell activation inhibitors

Abatacept

• Powder for solution for infusion vials 250mg
• Solution for injection pre-filled syringes 125mg/1ml

Notes

1. NICE TA195 Adalimumab, etanercept, infliximab, rituximab, and abatacept are recommended for the treatment of rheumatoid arthritis after the failure of a TNF inhibitor (August 2010).
2. NICE TA373 Abatacept, adalimumab, etanercept and tocilizumab are recommended as possible treatments for people with polyarticular juvenile idiopathic arthritis (NHS England Commissioned) (December 2015).

Tumour Necrosis Factor Alpha (TNF-α) inhibitors

NICE TA375: Adalimumab, etanercept, infliximab, certolizumab pegol, golimumab, tocilizumab and abatacept are recommended for rheumatoid arthritis not previously treated with DMARDs or after conventional DMARDs only have failed (January 2016):

• Adalimumab, etanercept, infliximab, certolizumab pegol, golimumab, tocilizumab and abatacept, all in combination with methotrexate, are recommended as options for treating rheumatoid arthritis, only if:
  • disease is severe, that is, a disease activity score (DAS28) greater than 5.1 and
  • disease has not responded to intensive therapy with a combination of conventional disease‑modifying antirheumatic drugs (DMARDs) and
  • the companies provide certolizumab pegol, golimumab, abatacept and tocilizumab as agreed in their patient access schemes.
• Adalimumab, etanercept, certolizumab pegol or tocilizumab can be used as monotherapy for people who cannot take methotrexate because it is contraindicated or because of intolerance, when the above criteria are met.
• Refer to TA375 for continuation criteria and other considerations.

NICE TA383: TNF-alpha inhibitors for ankylosing spondylitis and non-radiographic axial spondyloarthritis (February 2016):

• Adalimumab, certolizumab pegol, etanercept, golimumab and infliximab are recommended, within their marketing authorisations, as options for treating severe active ankylosing spondylitis in adults whose disease has responded inadequately to, or who cannot tolerate, non‑steroidal anti‑inflammatory drugs. Infliximab is recommended only if treatment is started with the least expensive infliximab product.
• Adalimumab, certolizumab pegol and etanercept are recommended, within their marketing authorisations, as options for treating severe non‑radiographic axial spondyloarthritis in adults whose disease has responded inadequately to, or who cannot tolerate, non‑steroidal anti‑inflammatory drugs.
• Refer to TA383 for continuation criteria and other considerations.
• Treatment with another tumour necrosis factor (TNF)‑alpha inhibitor is recommended for people who cannot tolerate, or whose disease has not responded to, treatment with the first TNF‑alpha inhibitor, or whose disease has stopped responding after an initial response.

NICE TA715: Adalimumab, etanercept, infliximab and abatacept for treating moderate rheumatoid arthritis after conventional DMARDs have failed (July 2021):

• Adalimumab, etanercept and infliximab, all with methotrexate, are recommended as options for treating active rheumatoid arthritis in adults, only if:
  • intensive therapy with 2 or more conventional disease-modifying antirheumatic drugs (DMARDs) has not controlled the disease well enough and
  • disease is moderate (a disease activity score [DAS28] of 3.2 to 5.1) and
  • the companies provide adalimumab, etanercept and infliximab at the same or lower prices than those agreed with the Commercial Medicines Unit.
• Adalimumab and etanercept can be used as monotherapy when methotrexate is contraindicated or not tolerated, when the criteria above are met.
• Refer to TA715 for continuation criteria and other considerations.
• Abatacept with methotrexate is not recommended, within its marketing authorisation, for treating moderate active rheumatoid arthritis in adults when 1 or more DMARDs has not controlled the disease well enough.

Adalimumab

• Injection 40mg

Notes

1. Prescribe by brand. A biosimilar medicine is a biological medicine that is highly similar and clinically equivalent (in terms of quality, safety, and efficacy) to an existing biological medicine however they cannot be considered generic equivalents of the originator biological medicine. Because they are not identical, biological medicines must be prescribed by brand. The decision which brand to prescribe rests with the responsible clinician in consultation with the patient. Automatic substitution of brands at the point of dispensing is not appropriate for biological medicines.
2. NICE TA195: Adalimumab, etanercept, infliximab, rituximab, and abatacept for the treatment of rheumatoid arthritis after the failure of a TNF inhibitor (August 2010).
3. NICE TA199: Psoriatic arthritis - etanercept, infliximab and adalimumab (August 2010).
4. NICE TA373: Abatacept, adalimumab, etanercept and tocilizumab are recommended as possible treatments for people with polyarticular juvenile idiopathic arthritis. Adalimumab and etanercept are recommended as possible treatments for people with enthesitis-related juvenile idiopathic arthritis (NHS England Commissioned) (December 2015).
5. NICE TA392: Adalimumab recommended for treating moderate to severe hidradenitis suppurativa (June 2016) (NHS England commissioned).
6. NICE TA455: Adalimumab, etanercept and ustekinumab for treating plaque psoriasis in children and young people (July 2017).
7. NICE TA460: Adalimumab and dexamethasone for treating non-infectious uveitis (July 2017).

Certolizumab pegol

• Solution for injection pre-filled syringes 200mg/1ml

Notes

1. NICE TA415: Certolizumab pegol (Cimzia), in combination with methotrexate, is recommended as an option for treating active rheumatoid arthritis in adults whose disease has responded inadequately to, or who cannot tolerate, other disease-modifying antirheumatic drugs (DMARDs) including at least 1 tumour necrosis factor‑alpha (TNF‑alpha) inhibitor, only when the criteria of the NICE TA are met (October 2016).
2. NICE TA445: Certolizumab pegol and secukinumab for treating active psoriatic arthritis after inadequate response to DMARDs (May 2017):
   1. Certolizumab pegol (Cimzia) alone, or in combination with methotrexate, is recommended as an option for treating active psoriatic arthritis in adults, only when the criteria of the NICE TA are met.
3. NICE TA574: Certolizumab pegol (Cimzia) is recommended as an option for treating plaque psoriasis in adults, only when the criteria of the NICE TA are met (April 2019).

Etanercept

• Paediatric powder and solvent for solution injection vials 10mg
• Powder and solvent for solution for injection vials 25mg, 50mg
• Solution for injection pre-filled syringes 25mg/0.5ml, 50mg/1ml

Notes

1. Prescribe by brand. A biosimilar medicine is a biological medicine that is highly similar and clinically equivalent (in terms of quality, safety, and efficacy) to an existing biological medicine however they cannot be considered generic equivalents of the originator biological medicine. Because they are not identical, biological medicines must be prescribed by brand. The decision which brand to prescribe rests with the responsible clinician in consultation with the patient. Automatic substitution of brands at the point of dispensing is not appropriate for biological medicines.
2. Once commenced on therapy, etanercept should be brand prescribed to ensure continuity of supply for patients.
3. NICE TA195: Adalimumab, etanercept, infliximab, rituximab, and abatacept for the treatment of rheumatoid arthritis after the failure of a TNF inhibitor (August 2010).
4. NICE TA199: Psoriatic arthritis - etanercept, infliximab and adalimumab (August 2010).
5. NICE TA373: Abatacept, adalimumab, etanercept and tocilizumab are recommended as possible treatments for people with polyarticular juvenile idiopathic arthritis. Etanercept is recommended as a possible treatment for people with psoriatic juvenile idiopathic arthritis (NHS England Commissioned) (December 2015).
6. NICE TA455: Adalimumab, etanercept and ustekinumab for treating plaque psoriasis in children and young people (July 2017).

Golimumab

• Solution for injection pre-filled syringes 50mg/0.5ml
• Solution for injection pre-filled pens 50mg/0.5ml, 100mg/1ml

Notes

1. NICE TA220: Psoriatic arthritis – golimumab (April 2011).
2. NICE TA225: Rheumatoid arthritis (after the failure of previous anti-rheumatic drugs) – golimumab (partially updated by TA375) (June 2011).
3. NICE TA497: Golimumab is recommended for treating severe non-radiographic axial spondyloarthritis (January 2018).
   

Infliximab

• Powder for solution for infusion vials 100mg

Notes

1. Prescribe by brand. A biosimilar medicine is a biological medicine that is highly similar and clinically equivalent (in terms of quality, safety, and efficacy) to an existing biological medicine however they cannot be considered generic equivalents of the originator biological medicine. Because they are not identical, biological medicines must be prescribed by brand. The decision which brand to prescribe rests with the responsible clinician in consultation with the patient. Automatic substitution of brands at the point of dispensing is not appropriate for biological medicines.
2. Once commenced on therapy, infliximab should be brand prescribed to ensure continuity of supply for patients.
3. NICE TA195: Adalimumab, etanercept, infliximab, rituximab, and abatacept for the treatment of rheumatoid arthritis after the failure of a TNF inhibitor (August 2010).
4. NICE TA199: Psoriatic arthritis - etanercept, infliximab and adalimumab (August 2010).
5. NICE TA329: Infliximab, adalimumab and golimumab for treating moderately to severely active ulcerative colitis after the failure of conventional therapy (February 2015).

Interleukin inhibitors

Anakinra

• Solution for injection pre-filled syringes 100mg/0.67ml

Notes

1. NICE TA685: Anakinra (Kineret) is recommended as an option for treating Still's disease with moderate to high disease activity, or continued disease activity after non-steroidal anti-inflammatory drugs (NSAIDs) or glucocorticoids (March 2021). It is only recommended for:
   1. adult-onset Still's disease that has responded inadequately to 2 or more conventional disease‑modifying antirheumatic drugs (DMARDs).
   2. systemic juvenile idiopathic arthritis in people 8 months and older with a body weight of 10 kg or more that has not responded to at least 1 conventional DMARD.

Sarilumab

• Solution for injection pre-filled syringes 150mg/1.14ml, 200mg/1.14ml
• Solution for injection pre-filled pens 150mg/1.14ml, 200mg/1.14ml

Notes

1. An interim clinical commissioning policy has been put in place to define routine access to sarilumab for the treatment of COVID-19 across the UK.
   1. Sarilumab is recommended as an alternative treatment option for adults (aged 18 years and over) hospitalised with COVID-19 if tocilizumab is unavailable for this indication or cannot be used and the criteria set out in the interim policy are met (29 November 2022). See also clinical guide (CEM/CMO/2022/018).
   2. Sarilumab is to be delivered as a once-only intravenous infusion. Sarilumab is available as a pre-filled syringe. Information on dose and administration is included in the policy.
   3. Sarilumab should not be used during pregnancy unless clinically necessary. Women of childbearing potential should use effective contraception during and up to 3 months after treatment. Clinicians are advised to refer to the Summary of Product Characteristics for sarilumab for more information on pregnancy and lactation.
   4. Information on co-administration with other treatments for COVID-19 is included in the policy.
   5. Pre-authorised use of sarilumab for individual patients with COVID-19 is required using Blueteq (CEM/CMO/2022/018).
   6. For information on recording the use of tocilizumab in discharge letters to primary care, see CEM/CMO/2022/018.
   7. Contact the hospital pharmacy department before prescribing to determine availability.
   8. Use of sarilumab by intravenous infusion for the treatment of COVID-19 is off-label. Torbay and South Devon NHS Foundation Trust and University Hospitals Plymouth NHS Trust have given approval for use of sarilumab by intravenous infusion for COVID-19.
2. NICE TA485: Sarilumab for moderate to severe rheumatoid arthritis (November 2017).

Tocilizumab

• Solution for injection pre-filled syringes 162mg/0.9ml
• Solution for injection pre-filled pens 162mg/0.9ml
• Solution for infusion vials 80mg/4ml, 200mg/10ml, 400mg/20ml

Notes

1. The commissioning of tocilizumab subcutaneous injection is accepted in Devon as an alternative treatment option to tocilizumab intravenous infusion for the treatment of rheumatoid arthritis where use is in line with NICE guidance for tocilizumab (NICE TA247 and NICE TA375) (see Commissioning Policy for more details).
2. NICE TA238: Tocilizumab (RoActemra) is recommended for the treatment of systemic juvenile idiopathic arthritis in children and young people aged 2 years and older whose disease has responded inadequately to non-steroidal anti-inflammatory drugs (NSAIDs), systemic corticosteroids and methotrexate (December 2011).
3. NICE TA247: Tocilizumab (RoActemra) in combination with methotrexate is recommended as an option for the treatment of rheumatoid arthritis in adults, only when the criteria of the NICE TA are met (February 2012).
4. NICE TA373: Abatacept (Orencia), adalimumab (Humira), etanercept (Enbrel) and tocilizumab (RoActemra) are recommended as options for treating polyarticular juvenile idiopathic arthritis (JIA), including polyarticular‑onset, polyarticular‑course and extended oligoarticular JIA (December 2015).
5. NICE TA375: Adalimumab (Humira), etanercept (Enbrel), infliximab (Remicade, Remsima, Inflectra), certolizumab pegol (Cimzia), golimumab (Simponi), tocilizumab (RoActemra) and abatacept (Orencia), all in combination with methotrexate, are recommended as options for treating rheumatoid arthritis, only when the criteria of the NICE TA are met (January 2016).
6. NICE TA518: Tocilizumab (RoActemra) when used with a tapering course of glucocorticoids (and when used alone after glucocorticoids), is recommended as an option for treating giant cell arteritis in adults, only when the criteria of the NICE TA are met (April 2018).
7. NICE TA878: Casirivimab plus imdevimab, nirmatrelvir plus ritonavir, sotrovimab and tocilizumab for treating COVID-19 (March 2023):
   1. Tocilizumab is recommended, within its marketing authorisation, as an option for treating COVID-19 in adults who:
      1. are having systemic corticosteroids and
      2. need supplemental oxygen or mechanical ventilation.
   2. Tocilizumab is only recommended if the company provides it according to the commercial arrangement.
8. MHRA Drug Safety Update (July 2019): rare risk of serious liver injury including cases requiring transplantation
   1. rare but serious cases of drug-induced liver injury, including acute liver failure and hepatitis, have been reported in patients treated with tocilizumab; some cases required liver transplantation.
   2. advise patients to seek medical help immediately if they experience signs and symptoms of liver injury, such as tiredness, abdominal pain, and jaundice.
   3. monitor alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels at initiation, every 4–8 weeks during the first 6 months of treatment, and every 12 weeks thereafter in patients with rheumatological indications.
   4. exercise caution when considering treatment initiation in patients with ALT or AST higher than 1.5-times the upper limit of normal (ULN); initiation of treatment is not recommended in patients with ALT or AST higher than 5-times the ULN.
   5. if liver enzyme abnormalities are identified, consult the dose modifications recommended, which have not changed.

Ustekinumab

• Solution for injection vials 45mg/0.5ml
• Solution for injection pre-filled syringes 45mg/0.5ml, 90mg/1ml
• Solution for infusion vials 130mg/26ml

Notes

1. NICE TA180: Ustekinumab (Stelara) is recommended as a treatment option for adults with plaque psoriasis, only when the criteria of the NICE TA are met (September 2009).
2. NICE TA340: Ustekinumab (Stelara) is recommended as an option, alone or in combination with methotrexate, for treating active psoriatic arthritis in adults, only when the criteria of the NICE TA are met (June 2015).
3. NICE TA455: Adalimumab (Humira), etanercept (Enbrel) and ustekinumab (Stelara) for treating plaque psoriasis in children and young people (July 2017):Ustekinumab (Stelara) is recommended as an option for treating plaque psoriasis in children and young people aged 12 years or older, only if the disease:
   1. is severe, as defined by a total PASI of 10 or more
   2. has not responded to standard systemic therapy, such as ciclosporin, methotrexate or phototherapy, or these options are contraindicated or not tolerated.
4. NICE TA456: Ustekinumab (Stelara) is recommended, within its marketing authorisation, as an option for treating moderately to severely active Crohn's disease, that is, for adults who have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a TNF‑alpha inhibitor or have medical contraindications to such therapies (July 2017).
5. NICE TA633: Ustekinumab (Stelara) is recommended as an option for treating moderately to severely active ulcerative colitis in adults when conventional therapy or a biological agent cannot be tolerated, or the disease has responded inadequately or lost response to treatment, only when the criteria of the NICE TA are met (June 2020).