10.1. Drugs used in rheumatic diseases and gout
10.1.1. Non-steroidal anti-inflammatory drugs
Restrictions:
Use of MR preparations is restricted. Modified-release preparations of any NSAID should be restricted to patients with early morning stiffness or compliance problems as they encourage regular/higher doses of NSAIDs and do not afford flexibility in reducing the dose.
Prescribing Notes:
There is a significant cost difference between the tablets and the enteric coated tablets.
Restrictions:
Use of MR preparations is restricted. Modified-release preparations of any NSAID should be restricted to patients with early morning stiffness or compliance problems as they encourage regular/higher doses of NSAIDs and do not afford flexibility in reducing the dose.
Prescribing Notes:
In June 2013, the MHRA issued new contraindications and warnings for diclofenac following a review of the cardiovascular risk, which it states is similar to that of the selective COX-2 inhibitors. A summary of the guidance on the MHRA website is available HERE
Restrictions:
Restricted to use in acute gout only. Other indications, including the use in the treatment of ankylosing spondylitis which has not been accepted by SMC, are non-Formulary.
10.1.2. musculoskeletal-corticosteroids
10.1.2.1. Systemic corticosteroids
10.1.2.2. Local corticosteroid injections
10.1.3. Drugs that suppress the rheumatic disease process
Restrictions:
Restricted to specialist initiation.
Prescribing Notes:
Oral methotrexate should only be prescribed as 2.5mg tablets to avoid patient confusion. The dose should be clearly specified on the dispensing label. In view of reports of blood dyscrasias (including fatalities) and liver cirrhosis with low-dose methotrexate, the CSM has advised: - full blood count and renal and liver function tests before starting treatment and repeated weekly until therapy stabilised, thereafter patients should be monitored every 2-3 months. - that patients should be advised to report all symptoms and signs suggestive of infection, especially sore throat.
Near Patient Testing (NPT) arrangements for GPs may be in place for this medicine. See the relevant section in the Prescribing Resources page for current information.
Prescribing Notes:
The CSM has advised that patients should be advised to report any unexplained bleeding, bruising, purpura, sore throat, fever or malaise (potential signs of blood dyscrasia).
Near Patient Testing (NPT) arrangements for GPs may be in place for this medicine. See the relevant section in the Prescribing Resources page for current information.
Restrictions:
Restricted to specialist use in combination with methotrexate for adult patients with active rheumatoid arthritis as measured by a disease activity score (DAS28) greater than 5.1 confirmed on at least two occasions 1 month apart who have responded inadequently to previous therapy with one or more disease-modifying anti-rheumatic drugs including methotrexate or a TNF-alpha inhibitor.
Prescribing Notes:
The following indications are not recommended by SMC and remain non-Formulary
- The treatment of patients with RA not previously treated with methotrexate
- With methotrexate for the treatment of patients with moderate rheumatoid arthritis (see NICE TA715 for further information)
- Alone, or in combination with methotrexate, for the treatment of active psoriatic arthritis in adults when the response to previous disease-modifying anti-rheumatic drug (DMARD) therapy including methotrexate, has been inadequate, and for whom additional systemic therapy for psoriatic skin lesions is not required.
Restrictions:
Restricted to specialist use only in accordance with the prescribing notes below.
Prescribing Notes:
Adalimumab should be prescribed by brand name. Amgevita® is the preferred biosimilar.
Rheumatoid Arthritis
- Adalimumab, in combination with methotrexate, may be used for the treatment of severe arthritis in accordance with local guidelines.
- Adalimumab, in combination with methotrexate, may be used for the treatment of moderate arthritis in accordance with local guidelines only if:
-
intensive therapy with 2 or more conventional disease-modifying antirheumatic drugs (DMARDs) has not controlled the disease well enough and
- a disease activity score [DAS28] of 3.2 to 5.1
- See NICE TA715 for further guidance relating to use in moderate disease.
-
- Adalimumab can be used as monotherapy when methotrexate is contraindicated or not tolerated for moderate to severe arthritis as indicated above.
Ankylosing Spondylitis
- Use for ankylosing spondylitis is restricted to use in accordance with the British Society for Rheumatology guidelines of July 2004.
Axial Spondyloarthritis
- The treatment of adults with severe axial spondyloarthritis without radiographic evidence of ankylosing spondylitis but with objective signs of inflammation by elevated C-reactive protein (CRP) and/or magnetic resonance imaging (MRI), who have had an inadequate response to, or are intolerant to non-steroidal anti-inflammatory drugs (NSAIDs) is restricted to specialist use in accordance with Assessment in Spondyloarthritis Internation Society (ASIS) guidance.
Active polyarticular idiopathic arthritis
- Use for active polyarticular idiopathic arthritis in adolescents aged 13-17 years is restricted to those who have an inadequate response to one or more DMARDs.
For the use in other indications, see sections 1.5.3, 11.8 and 13.5.3
Restrictions:
Restricted to specialist use and the indications listed under Prescribing Notes below.
Prescribing Notes:
Formulary indications:
- Treatment of Still's disease, including Systematic Juvenile Idiopathis Arthritis (SJIA) and Adult-Onset Still's Diease (AOSD), in adults and adolescents with active systemic features of moderate to high disease activity, or in patients with continued disease activity after treatment with non-steroidal anti-inflammatory drugs (NSAIDs) or glucocorticosteroids. Anakinra can be given as monotherapy or in combination with other anti-inflammatory and disease-modifying anti-rheumatic drugs (DMARDs).
Non-formulary indications:
- Treatment of rheumatoid arthritis is not recommended by SMC.
- Treatment of Cryopyrin-Associated Periodic Syndromes (CAPS) in adults and adolescents is not recommended by SMC.
- Treatment of Familial Mediterranean Fever (FMF) is not recommended by SMC.
Restrictions:
Use in the treatment of Psoriatic Arthritis (PsA) is restricted to specialist initiation in adults with active psoriatic athritis who have had an inadequate response with at least two prior disease modifying anti-rheumatics drugs (DMARDs) or who are intolerant to such therapies.
Prescribing Notes:
- Specialist secondary care clinics continue to have responsibility for:
- providing prescription for the initiation pack
- all monitoring
- assessment of response
- GPs can obtain advice from specialist clinics (contact details provided with each patient request)
- Further information can be found in the accompanying GP Information sheet
For other indications please see chapter 13.5.3
Restrictions:
Restricted to specialist initiation.
Prescribing Notes:
Near Patient Testing (NPT) arrangements for GPs may be in place for this medicine. See the relevant section in the Prescribing Resources page for current information.
Restrictions:
Use in rheumatoid athritis is restricted to specialist use in patients with severe disease (a disease activity score [DAS28] >5.1) that has not responded to intensive therapy with at least two conventional DMARDs including methotrexate. In patients with severe disease inadequately controlled by a tumour necrosis factor (TNF) antagonist, it may be used in patients ineligible to receive rituximab.
Prescribing Notes:
Where a JAK inhibitor is the selected treatment option, baricitinib would be the preferred choice in NHSGGC.
Following a MHRA review in April 2023, the risk of increased incidence of malignancy, major adverse cardiovascular events (MACE), serious infections, venous thromboembolism (VTE) and mortality, when compared to those treated with tumour necrosis factor (TNF)-alpha inhibitors, were are considered a class effects across JAK inhibitors used for chronic inflammatory disorders and therefore it is advised to avoid prescribing these medicines unless there are no suitable alternatives in patients with the following risk factors:
- age 65 years or older
- current or past long-time smoking
- other risk factors for cardiovascular disease or malignancy
Please see further details of the review here.
Restrictions:
Restricted to specialist use for the following indications:
- in patients with evidence of serological disease activity (i.e. positive anti-dsDNA and low complement) and a Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) score of ≥10.
- as add-on therapy in adult patients with evidence for at least one marker of serological disease activity (low complement, positive anti-dsDNA) and a Safety of Estrogens in Lupus Erythematosus National Assessment-
Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) score ≥10.
Prescribing Notes:
Use in combination with background immunosuppressive therapies for the treatment of adult patients with active lupus nephritis is not recommended by SMC and is non-Formulary.
Restrictions:
Restricted to specialist use for the following indications:
Psoriatic Arthritis
Alone or in combination with methotrexate, for the treatment of active psoriatic arthritis in adults who have had an inadequate response or who have been intolerant to two conventional disease-modifying antirheumatic drugs (DMARDs), given either along or in combination.
Axial spondyloarthritis
- For the treatment of adults with active non-radiographic axial spondyloarthritis with objective signs of inflammation as indicated by elevated C-reactive protein (CRP) and/or magnetic resonance imaging (MRI) who have responded inadequately or are intolerant to non-steroidal anti-inflammatory drugs (NSAIDs).
- For the treatment of adults with active ankylosing spondylitis who have responded inadequately or are intolerant to conventional therapy.
Restrictions:
Restricted to specialist use only for the indications as outlined below in the Prescribing Notes section:
Prescribing Notes:
Formulary indications and restrictions:
- Moderate to severe active rheumatoid arthritis in combination with methotrexate in adult patients when the response to disease modifying anti-rheumatic drugs, including methotrexate, has been inadequate and monotherapy in case of intolerance to methotrexate or when continued treatment with methotrexate is inappropriate
- The treatment of adult patients with severe active axial spondyloarthritis, comprising (1) Ankylosing spondylitis (AS) and (2) Axial spondyloarthritis without radiographic evidence of AS (nr-axSpA)
- Active psoriatic arthritis is restricted to specialist use in patients whose disease has not responded to adequate trials of at least two standard DMARDs either individually or in combination. It may be used in combination with methotrexate or as monotherapy in cases of intolerance to methotrexate or when continued treatment with methotrexate is inappropriate.
Non-formulary indications:
- Treatment of severe, active and progressive RA in adults not previously treated with MTX or other DMARDs.
For indications in dermatology, see section 13.5.3
Restrictions:
Restricted to specialist initiation. Restricted to specialist use for refractory patients.
Prescribing Notes:
Prescribe by brand name.
Restrictions:
Restricted to specialist use only.
In adults, etanercept is restricted to initiation by consultant rheumatologists for:
Rheumatoid arthritis
- In combination with methotrexate, may be used for the treatment of severe arthritis in accordance with local guidelines.
- In combination with methotrexate, may be used for the treatment of moderate arthritis in accordance with local guidelines only if:
-
intensive therapy with 2 or more conventional disease-modifying antirheumatic drugs (DMARDs) has not controlled the disease well enough and
- a disease activity score [DAS28] of 3.2 to 5.1
- See NICE TA715 for further guidance relating to use in moderate disease.
-
- Can be used as monotherapy when methotrexate is contraindicated or not tolerated for moderate to severe arthritis as indicated above
Ankylosing spondylitis
- restricted to use in accordance with the British Society for Rheumatology (BSR) guidelines of July 2004.
Axial spondyloarthritis
- restricted to specialist use in accordance with the recommendations made in NICE TA 383 click here
Prescribing Notes:
Etanercept should be prescribed by brand name. Benepali® is the preferred biosimilar.
Restrictions:
Restricted to specialist use in accordance with local guidance for use in patients with moderate (DAS28 of 3.2 to 5.1) or severe disease (DAS28 greater than 5.1) that has not responded to intensive therapy with a combination of conventional DMARDs and in patients with severe disease inadequately controlled by a TNF antagonist in whom rituximab is not appropriate.
Prescribing Notes:
Following a MHRA review in April 2023, the risk of increased incidence of malignancy, major adverse cardiovascular events (MACE), serious infections, venous thromboembolism (VTE) and mortality, when compared to those treated with tumour necrosis factor (TNF)-alpha inhibitors, were are considered a class effects across JAK inhibitors used for chronic inflammatory disorders and therefore it is advised to avoid prescribing these medicines unless there are no suitable alternatives in patients with the following risk factors:
- age 65 years or older
- current or past long-time smoking
- other risk factors for cardiovascular disease or malignancy
Please see further details of the review here.
Restrictions:
Golimumab is included in the Formulary for use in specific patient groups in ankylosing spondylitis, psoriatic arthritis, rheumatoid arthritis and axial spondyloarthritis in accordance with SMC advice/local formulary restrictions as detailed in the prescribing notes below.
Prescribing Notes:
Ankylosing spondylitis:
The treatment of severe active ankylosing spondylitis in adults is restricted to use in accordance with the British Society of Rheumatology guidelines.
For the relevant SMC advice for ankylosing spondylitis click here
Psoriatic Arthritis:
Use in combination with methotrexate, for the treatment of active and progressive psoriatic arthritis in adult patients when the response to previous disease-modifying anti-rheumatic drug (DMARD) therapy has been inadequate is restricted to specialist use in patients whose disease has not responded to adequate trials of at least two standard DMARDs, administered either individually or in combination. .
For the relevant SMC advice for psoriatic arthritis click here
Rheumatoid Arthritis:
The use in combination with methotrexate, for the treatment of moderate to severe, active rheumatoid arthritis is restricted to use in accordance with the British Society for Rheumatology (BSR) guidelines (2005).
For relevant SMC advice for rheumatoid arthritis click here
Axial Spondyloarthritis:
The treatment of adults with severe, active non-radiographic axial spondyloarthritis with objective signs of inflammation as indicated by elevated C-reactive protein (CRP) and/or magnetic resonance imaging (MRI) evidence, who have had an inadequate response to, or are intolerant to non-steroidal anti-inflammatory drugs (NSAIDs) is restricted to specialist use.
For the relevant SMC advice for axial spondyloarthritis click here
Restrictions:
Use in combination with methotrexate for the treatment of active psoriatic arthritis is restricted to specialist use in:
- Patients whose disease has not responded adequately or who have been intolerant to two previous
conventional DMARD therapies but have not received biologic DMARD therapy (biologic-naïve
population) - Patients whose disease has not responded adequately to conventional DMARDs and one or more
tumour necrosis factor (TNF) inhibitors (biologic-experienced population); and - Patients in whom TNF inhibitors are contraindicated or not tolerated.
Restrictions:
Restricted to specialist use only.
In adults, infliximab is restricted to initiation by consultant rheumatologists for the following:
Rheumatoid arthritis
- In combination with methotrexate, may be used for the treatment of severe arthritis in accordance with local guidelines.
- In combination with methotrexate, may be used for the treatment of moderate arthritis in accordance with local guidelines only if:
-
intensive therapy with 2 or more conventional disease-modifying antirheumatic drugs (DMARDs) has not controlled the disease well enough and
- a disease activity score [DAS28] of 3.2 to 5.1
- See NICE TA715 for further guidance relating to use in moderate disease.
-
- Can be used as monotherapy when methotrexate is contraindicated or not tolerated for moderate to severe arthritis as indicated above
Psoriatic arthritis
- Restricted to criteria set out in NICE Technology Appraisal 104.
Ankylosing spondylitis
- Restricted to use in accordance with recommendations made in the NICE TA 383 click here.
Prescribing Notes:
Infliximab should be prescribed by brand name. Remsima® is the preferred biosimilar.
Restrictions:
Ixekizumab as monotherapy or in combination with methotrexate for the treatment of active psoriatic athritis in adults is restricted to specialist use in accordance with local guidelines.
Prescribing Notes:
Use for the following is not recommended by SMC and is non-Formulary
- Ankylosing spondyloarthritis (radiographic axial spondyloarthritis)
- Treatment of adult patients with active ankylosing spondylitis who have responded inadequately to conventional therapy.
- Treatment of adult patients with active non-radiographic axial spondyloarthritis with objective signs of inflammation as indicated by elevated C-reactive protein (CRP) and/or magnetic resonance imaging (MRI) who have responded inadequately to nonsteroidal anti-inflammatory drugs (NSAIDs).
For the use of ixekizumab in psoriasis, see section 13.5.3.
Restrictions:
Restricted to specialist initiation. In adults, leflunomide is restricted to initiation by consultant rheumatologists.
Prescribing Notes:
Near Patient Testing (NPT) arrangements for GPs may be in place for this medicine. See the relevant section in the Prescribing Resources page for current information.
Restrictions:
To be initiated and supervised by a specialist, though GPs are able to continue prescribing.
Restrictions:
Restricted to specialist initiation. This is an unlicensed indication of minocycline and is restricted to initiation by consultant rheumatologists for use in patients who could not be successfully treated with other DMARDs or anti-TNF therapy because of sepsis.
Restrictions:
Use for active psoriatic arthritis is restricted to specialist use in:
- patients whose disease has not responded adequately or who have been intolerant to two previous
conventional disease-modifying antirheumatic drug (DMARD) therapies but have not received biologic
DMARD therapy (biologic-naïve population) - patients whose disease has not responded adequately to conventional DMARDs and one or more
tumour necrosis factor (TNF) inhibitors (biologic-experienced population) and - patients in whom TNF inhibitors are contraindicated or not tolerated.
Restrictions:
Restricted to specialist use only. Use in rheumatoid arthritis is restricted to specialist use in accordance with local protocol.
Restrictions:
The use in the treatment of active rheumatoid athritis is restricted to patients with severe disease (a disease activity score [DAS28] greater than 5.1) that has not responded to intensive therapy with a combination of conventional disease-modifying anti-rheumatic drugs (DMARDs) including methotrexate. In patients with severe disease inadequately controlled by a TNF antagonist, it may be used in patients ineligible to receive rituxumab.
Prescribing Notes:
Where the treatment choice is an IL-6 inhibitor, then sarilumab is the preferred choice.
Restrictions:
Restricted to specialist use for the following indications:
- Treatment of psoriatic arthritis is restricted to specialist use only in patients whose disease has not responded to adequate trials of at least two standard DMADRs either individually or in combination
- Treatment of active ankylosing spondylitis (AS) in adults who have responded inadequately to conventional therapy
- Treatment of active non-radiographic axial spondyloarthritis with objective signs of inflammation as indicated by elevated C reactive protein and/or magnetic resonance imaging evidence in adults who have responded inadequately to non steroidal anti
inflammatory drugs
Prescribing Notes:
See section 13.5.3 for use in plaque psoriasis.
Restrictions:
Restricted to specialist initiation.
Prescribing Notes:
Near Patient Testing (NPT) arrangements for GPs may be in place for this medicine. See the relevant section in the Prescribing Resources page for current information.
Restrictions:
Specialist use only.
- Use for moderate to severe active rheumatoid arthritis in combination with methotrexate, or as monotherapy, in patients who are intolerant to methotrexate or where continued treatment with methotrexate is inappropriate, is restricted in accordance with the British Society of Rheumatology guidelines (2005).
- Treatment of Giant Cell Arteritis (GCA) in adults is restricted to use in accordance with local guidelines and is subject to a 12-month clinical stopping rule.
Prescribing Notes:
Non-formulary indications:
- Treatment of severe, active and progressive rheumatoid arthritis in adults not previously treated with methotrexate is not recommended by SMC.
Restrictions:
- Use in rheumatoid athritis is restricted to specialist use in patients with severe disease (a disease activity score [DAS28] >5.1) that has not responded to intensive therapy with at least two conventional DMARDs including methotrexate. In patients with severe disease inadequately controlled by a tumour necrosis factor (TNF) antagonist, it may be used in patients ineligible to receive rituximab
Psoriatic Arthritis:
- Use in combination with methotrexate for the treatment of active psoriatic arthritis in adults is restricted to use in accordance with local guidelines.
Ankylosing spondylitis:
- The treatment of active ankylosing spondylitis (AS) in patients who have responded inadequately to conventional therapy is restricted to use in accordance with local guidelines.
Prescribing Notes:
Where a JAK inhibitor is the selected treatment option, baricitinib would be the preferred choice in NHSGGC.
Following a MHRA review in April 2023, the risk of increased incidence of malignancy, major adverse cardiovascular events (MACE), serious infections, venous thromboembolism (VTE) and mortality, when compared to those treated with tumour necrosis factor (TNF)-alpha inhibitors, were are considered a class effects across JAK inhibitors used for chronic inflammatory disorders and therefore it is advised to avoid prescribing these medicines unless there are no suitable alternatives in patients with the following risk factors:
- age 65 years or older
- current or past long-time smoking
- other risk factors for cardiovascular disease or malignancy
Please see further details of the review here.
Restrictions:
Restricted to specialist use in accordance with local guidelines for the following indications:
- adult patients with rheumatoid arthritis with severe disease (a disease activity score [DAS28] greater than 5.1) that has not responded to intensive therapy with a combination of conventional DMARDs and in patients with severe disease inadequately controlled by a TNF antagonist in whom rituximab is not appropriate.
- adult patients with moderate disease (a disease activity score [DAS28] of 3.2 to 5.1) when intensive therapy with 2 or more conventional DMARDs has not controlled the disease well enough.
- adult patients with psoriatic arthritis whose disease has not responded adequately to at least two conventional DMARDs given alone or in combination.
- adult patients with active ankylosing spondylitis (AS) who have responded inadequately to conventional therapy.
- Treatment of active non-radiographic axial spondyloarthritis in patients with objective signs of inflammation as indicated by elevated CRP and/or MRI, who have responded inadequately to NSAIDs.
Prescribing Notes:
For use in atopic dermatitis please refer to chapter 13.5.3
Following a MHRA review in April 2023, the risk of increased incidence of malignancy, major adverse cardiovascular events (MACE), serious infections, venous thromboembolism (VTE) and mortality, when compared to those treated with tumour necrosis factor (TNF)-alpha inhibitors, were are considered a class effects across JAK inhibitors used for chronic inflammatory disorders and therefore it is advised to avoid prescribing these medicines unless there are no suitable alternatives in patients with the following risk factors:
- age 65 years or older
- current or past long-time smoking
- other risk factors for cardiovascular disease or malignancy
Please see further details of the review here.
Restrictions:
The use as monotherapy or in combination with methotrexate, for the treatment of active psoriatic arthritis in adult patients when the response to previous non-biological disease-modifying anti-rheumatic drug therapy has been inadequate, is restricted to specialist use in patients with active psoriatic arthritis who have failed on, or are unsuitable for, treatment with an anti-TNF drug
Prescribing Notes:
For use in psoriasis, see section 13.5.3 and use in Crohn's disease, see section 1.5.3.
10.1.4. Gout and cytotoxic-induced hyperuricaemia
Prescribing Notes:
Allopurinol alone should not be initiated during the acute phase as it may precipitate further attacks or make the gout worse.
Restrictions:
Etoricoxib is restricted to use only in acute gout in high risk patients. See section 10.1.1 in preferred list for CSM advice. All other indications are non-Formulary.
Restrictions:
Restricted to use as outlined in Prescribing Notes section below.
Prescribing Notes:
- Chronic hyperuricaemia: restricted to symptomatic patients whose uric acid levels have failed to respond adequately despite optimal dosing of allopurinol.
- Hyperuricaemia related to chemotherapy: prevention and treatment of hyperuricaemia in adult patients undergoing chemotherapy for haematologic malignancies is restricted to specialist use for patients at intermediate risk of tumour lysis syndrome (TLS) in whom allopurinol is either unsuitable or contraindicated, such as those intolerant of allopurinol or those in whom allopurinol is contraindicated, e.g. patients with renal impairment.
Restrictions:
Restricted to specialist use only. Restricted to use under the supervision of haematologists and oncologists and subject to NHSGGC protocol for adults and children.