Treatment algorithm
Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer
conventional synthetic disease-modifying anti-rheumatic drug (DMARD)
Patients with mild disease at presentation are usually started on a single conventional synthetic DMARD.[49][62][88]
The American College of Rheumatology and the National Institute of Health and Care Excellence (NICE) in the UK recommend first-line hydroxychloroquine treatment for patients with low disease activity over other DMARDs; it is better tolerated and has a more favourable risk profile in patients with rheumatoid arthritis (RA).[49][62]
Sulfasalazine is recommended over methotrexate as patients with low disease activity may wish to avoid adverse effects associated with methotrexate therapy. Methotrexate is recommended over leflunomide due to its greater dosing flexibility.[49] Treatment with methotrexate has been demonstrated to significantly reduce overall mortality for patients with RA, including cardiovascular and interstitial lung disease mortality.[98]
Folic acid supplementation can also be started at the same time as starting methotrexate, as a prophylactic measure to reduce the risk of some adverse effects.
[ 
]
Hepatitis B and C status, purified protein derivative (PPD), FBC, and LFTs need to be checked before starting DMARDs.
Primary options
hydroxychloroquine: 400-600 mg/day orally given in 1-2 divided doses initially, reduce dose to 200-400 mg/day after clinical response is obtained
MoreSecondary options
sulfasalazine: 0.5 to 1 g/day orally (enteric-coated) for 7 days initially, increase by 500 mg/day increments every week according to response, maximum 2 g/day given in 2-3 divided doses
OR
methotrexate: 7.5 mg orally once weekly (on the same day each week) initially, increase gradually according to response, maximum 20 mg/week
OR
leflunomide: low risk for hepatotoxicity or myelosuppression: 100 mg orally once daily for 3 days, followed by 20 mg once daily; high risk for hepatotoxicity or myelosuppression: 20 mg orally once daily without loading dose
Moreconventional synthetic disease-modifying anti-rheumatic drug (DMARD)
If the patient has moderate-to-severe disease with or without extra-articular manifestations (e.g., pleuritis, interstitial lung disease, pericarditis, inflammatory eye disease) with poor prognostic factors such as rheumatoid factor (RF) positivity and/or anti-cyclic citrullinated peptide (anti-CCP) antibodies, and radiographic evidence of bony erosions at presentation, a more aggressive approach to initial therapy may be needed.
Methotrexate monotherapy is the initial treatment of choice.[49][88] Evidence suggests that methotrexate administered subcutaneously is more effective than oral methotrexate. Oral administration is, however, preferred for patients initiating methotrexate, due to the ease of administration and similar bioavailability at typical starting doses.[49][101]
For patients who are not able to tolerate oral weekly methotrexate, a split dose of oral methotrexate over 24 hours or weekly subcutaneous injections, and/or an increased dose of folic acid, is recommended before switching to an alternative DMARD.[49]
Folic acid supplementation can also be started at the same time as starting methotrexate, as a prophylactic measure to reduce the risk of some adverse effects.
[ ]
If methotrexate cannot be used then leflunomide, hydroxychloroquine, or sulfasalazine are alternatives.[49][88]
Hepatitis B and C status, purified protein derivative (PPD), FBC, and LFTs need to be checked before starting DMARDs.
Primary options
methotrexate: 7.5 mg orally/subcutaneously once weekly (on the same day each week) initially, increase gradually according to response, maximum 20 mg/week
Secondary options
sulfasalazine: 0.5 to 1 g/day orally (enteric-coated) for 7 days initially, increase by 500 mg/day increments every week according to response, maximum 2 g/day given in 2-3 divided doses
OR
hydroxychloroquine: 400-600 mg/day orally given in 1-2 divided doses initially, reduce dose to 200-400 mg/day after clinical response is obtained
MoreOR
leflunomide: low risk for hepatotoxicity or myelosuppression: 100 mg orally once daily for 3 days, followed by 20 mg once daily; high risk for hepatotoxicity or myelosuppression: 20 mg orally once daily without loading dose
Morebiological agent or targeted synthetic DMARD
Additional treatment recommended for SOME patients in selected patient group
If the patient does not respond or has an inadequate response to methotrexate, a biological agent (e.g., a tumour necrosis factor [TNF]-alpha inhibitor, an interleukin 6 [IL-6] inhibitor, abatacept, or rituximab) or a targeted synthetic DMARD such as an oral Janus kinase (JAK) inhibitor (e.g., tofacitinib, baricitinib, upadacitinib) can be added to methotrexate, taking into account pertinent risk factors.[49][88][102][103][104][105][Evidence C]
One systematic review concluded that the combination of methotrexate with a biological agent does increase efficacy of treatment for people with rheumatoid arthritis (RA) compared with methotrexate treatment alone.[107] In absolute terms, 7 to 16 more people out of 100 may have increased overall likelihood of responding to treatment with combination therapy.[107]
Combination therapy with methotrexate in addition to certolizumab pegol, abatacept, or tocilizumab is generally well tolerated in people with early RA at 24 weeks.[108] Adverse effects tend to increase at the target dose, and these were more frequent in combination with tocilizumab compared with active conventional treatment, which included either methotrexate plus an oral corticosteroid, or methotrexate plus sulfasalazine plus hydroxychloroquine plus intra-articular corticosteroids at 24 weeks.[108]
TNF-alpha inhibitors (etanercept, infliximab, adalimumab, golimumab, and certolizumab pegol) have proven efficacy in placebo-controlled trials.[110][111]
[ ]
One network meta-analysis reported that biological agents in combination with methotrexate (with the exception of golimumab) were associated with significantly lower rates of radiographic progression at 1 year compared with methotrexate alone.[112]
In the UK, adalimumab, etanercept, or infliximab, added to methotrexate, is recommended for adult patients with moderate RA (a disease activity score [DAS28] of 3.2 to 5.1) who have an inadequate response with two or more conventional synthetic DMARDs.[113]
[ ]
Adalimumab and etanercept can be used as monotherapy for patients when methotrexate is contraindicated, or not tolerated, provided that the above criteria are met.[113]
TNF-alpha inhibitors are approved for use either with or without methotrexate depending on the specific drug; check local drug formulary for specific licence information.
TNF-alpha inhibitors have been associated with increased risk for serious infection (tuberculosis and other opportunistic infections) compared with synthetic DMARDs, and increased risk for treatment discontinuation.[114][115][116]
[ ]
[ ]
Lymphoma and other malignancies have been reported in patients treated with TNF-alpha inhibitors. However, systematic reviews and meta-analyses have not reported an increased risk of malignancy among patients with RA receiving TNF-alpha inhibitor therapy.[116][117][118][119][120][121] When evaluating relevant systematic reviews and meta-analyses, consider that studies subject to meta-analysis have typically been of short duration and increased long-term risk of malignancy cannot, therefore, be excluded; patients with a prior history of cancer may have been excluded from studies, making it difficult to extrapolate results to patients with a previous cancer. Ongoing research seeks to establish the effect of specific DMARDs on risk of malignancy, particularly risk for non-melanoma skin cancer and melanoma.[122]
Potential adverse effects associated with TNF-alpha inhibitors could be minimised by using an individualised dose reduction/withdrawal strategy once disease control has been established.
The results of two systematic reviews suggest that disease activity-guided dose tapering of TNF-alpha inhibitors is comparable to continuation of treatment with respect to the proportion of patients with persistent remission and may be comparable regarding disease activity, while discontinuation of TNF-alpha inhibitors is inferior to continuation of treatment with respect to disease activity, the proportion of participants with persistent remission, function, and minimal radiographic damage.[123][124]
Abatacept is a T-cell modulator approved for the treatment of moderately to severely active RA. It has similar safety and efficacy to the TNF-alpha inhibitors, and is indicated in patients who have an inadequate response to methotrexate.[138][139]
[ ]
Abatacept or adalimumab given subcutaneously with background methotrexate (as would usually be the case in clinical practice) have been shown to have similar efficacy, safety, and time to response in patients with active RA who were naive to biological agents and those who had an inadequate response to methotrexate.[139]
Evidence suggests that abatacept, as monotherapy or in combination with methotrexate, provides more effective disease control compared with conventional treatment (methotrexate with corticosteroids), methotrexate alone, biological agents or targeted synthetic DMARDs in patients with RA.[141][142]
[ ]
There is evidence demonstrating sustained remission with abatacept following dose reduction or complete drug withdrawal.[141][143] Few patients sustain a major response 1 year after withdrawal of abatacept therapy; re-treatment with abatacept plus methotrexate may be effective in this setting.[144]
Abatacept is recommended over other biological agents and targeted synthetic DMARDs for patients with non-tuberculous mycobacterial lung disease who have moderate-to-high disease activity despite conventional synthetic DMARDs.[49]
Rituximab is a B-cell modulator approved for use in combination with methotrexate for the treatment of adults with moderately to severely active RA who have had an inadequate response to one or more TNF-alpha inhibitors.
Rituximab is recommended over other DMARDs, regardless of previous DMARD experience, for patients who have a previous lymphoproliferative disorder (for which rituximab is an approved treatment), and who have moderate-to-high disease activity, because it would not be expected to increase the risk of recurrence or worsening of lymphoproliferative disorders.[49]
In the setting of persistent hypogammaglobulinaemia without infection, continuation of rituximab therapy for patients at target is conditionally recommended over switching to a different biological agent or targeted synthetic DMARD.[49] Continuing rituximab in patients who are at target is preferred due to the uncertain clinical significance of hypogammaglobulinaemia in patients without infection. Although an increased risk of infection has been described in RA patients with hypogammaglobulinaemia, it is not known if a switch in DMARDs in patients who are at target is more effective in lowering infection risk while maintaining disease control than continuation of rituximab.
Interleukin 6 (IL-6) inhibitors (e.g., tocilizumab and sarilumab) are approved for the treatment of adults with moderately to severely active RA who have had an inadequate response to one or more DMARDs.
They may be used as monotherapy, or in combination with methotrexate or other conventional synthetic DMARDs.[125][126]
Evidence from systematic reviews using indirect comparisons suggest that tocilizumab may be more effective than sarilumab for treating people with RA who inadequately respond to either methotrexate or TNF-alpha inhibitors.[128][129] An additional systematic review concluded that for people with RA with an inadequate response to conventional synthetic DMARDs, sarilumab monotherapy is more effective than adalimumab, biological agents and targeted synthetic DMARDs.[130]
One open-label randomised trial evaluated the efficacy and safety of increasing the dose interval of subcutaneous tocilizumab in patients with RA who are in remission.[131] The study reported that although most patients sustained remission with a half-dose of tocilizumab, increasing the dose interval to 2 weeks was associated with a lower likelihood of maintaining remission, with no improvement in tolerability.[131]
There is evidence to suggest that treatment with IL-6 inhibitors may increase the risk of serious infection, opportunistic infections, and cancer in patients with RA compared with placebo.[132] Tocilizumab has been associated with a drug-induced sarcoidosis-like reaction, occurring in temporal relationship with the initiation of tocilizumab, and a significant risk of the reactivation of hepatitis B virus (HBV) in people with RA and chronic HBV.[132][133][134][135]
The European Medicines Agency (EMA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA) identified serious hepatotoxicity (including acute liver failure, hepatitis, and jaundice) in eight patients treated with tocilizumab worldwide.[136][137]
Monitor alanine aminotransferase (ALT) or aspartate aminotransferase (AST) at initiation of treatment, every 4-8 weeks for the first 6 months of treatment, and then every 12 weeks thereafter.[136][137] Advise patients to seek medical help immediately if they experience signs and symptoms of hepatic injury.[137]
Targeted synthetic DMARDs include the oral Janus kinase (JAK) inhibitors tofacitinib, baricitinib, and upadacitinib, which are all approved to treat moderate to highly active RA.[49][150] Filgotinib, another selective inhibitor of JAK1, is approved in Europe and the UK for the treatment of moderate to severely active rheumatoid arthritis in adults who have responded inadequately to, or who are intolerant to, one or more DMARDs.
The US Food and Drug Administration (FDA) has issued a warning about an increased risk of serious cardiovascular events, malignancy, thrombosis, and death with tofacitinib, baricitinib, and upadacitinib.[145] This follows final results from a large randomised safety clinical trial comparing tofacitinib with tumour necrosis factor (TNF)-alpha inhibitors in patients with RA. The study found an increased risk of blood clots and death with the lower dose of tofacitinib (5 mg twice daily); this serious event had previously been reported only with the higher dose (10 mg twice daily) in the preliminary analysis.[146]
The FDA advises clinicians to reserve tofacitinib, baricitinib, and upadacitinib for patients who have had an inadequate response or are intolerant to one or more TNF-alpha inhibitors, and consider the patient's individual benefit-risk profile when deciding to prescribe or continue treatment with these medications, particularly in patients who are current or past smokers, patients with other cardiovascular risk factors, those who develop a malignancy, and those with a known malignancy (other than a successfully treated non-melanoma skin cancer).[145]
The European Medicines Agency (EMA) has also recommended measures to minimise the risk of serious adverse effects with JAK inhibitors. The EMA advice relates to patients aged >65 years, those who are current or past smokers, patients with other cardiovascular risk factors (such as heart attack or stroke), and patients with other malignancy risk factors. In these patient groups, JAK inhibitors should only be used to treat moderate or highly active RA, if no suitable treatment alternative is available.[147]
The EMA recommends that JAK inhibitors should be used with caution in patients with risk factors for blood clots in the lungs and in deep veins (venous thromboembolism, VTE); and that doses should be reduced in patient groups who are at risk of VTE, cancer, or major cardiovascular problems, if possible. This recommendation is based on one observational study comparing the safety of baricitinib with TNF-alpha inhibitors.[147][148]
In the UK, the National Institute for Health and Care Excellence (NICE) has recommended filgotinib (a JAK1 inhibitor) in combination with methotrexate as an option for adult patients with moderate to severe RA (i.e., a disease activity score [DAS28] of 3.2 or more), who have an inadequate response to intensive therapy with two or more conventional synthetic DMARDs.[149]
For patients with severe disease (DAS28 of more than 5.1) NICE recommends filgotinib with methotrexate as an option if the patient cannot tolerate rituximab and has responded inadequately to or cannot have other DMARDs, including at least one biological DMARD, or if the patient has an inadequate response to rituximab and at least one biological DMARD.[149]
Filgotinib can be used as monotherapy in a patient with a contraindication to or intolerance of methotrexate when the above criteria are met.[149][150]
Primary options
etanercept: 50 mg subcutaneously once weekly; or 25 mg subcutaneously twice weekly
OR
infliximab: 3 mg/kg intravenous infusion at weeks 0, 2, 6, and then every 8 weeks thereafter
MoreOR
adalimumab: 40 mg subcutaneously every 2 weeks
OR
certolizumab pegol: 400 mg subcutaneously at weeks 0, 2, and 4, and then 200 mg every 2 weeks or 400 mg every 4 weeks thereafter
OR
golimumab: 50 mg subcutaneously once monthly; or 2 mg/kg intravenous infusion at weeks 0 and 4, and then every 8 weeks thereafter
OR
abatacept: body weight <60 kg: 500 mg intravenous infusion at weeks 0, 2, and 4, and then every 4 weeks thereafter; body weight 60-100 kg: 750 mg intravenous infusion at weeks 0, 2, and 4, and then every 4 weeks thereafter; body weight >100 kg: 1000 mg intravenous infusion at weeks 0, 2, and 4, and then every 4 weeks thereafter
MoreOR
rituximab: 1000 mg intravenous infusion on days 1 and 15, may repeat course every 16-24 weeks if inadequate response
OR
tocilizumab: 4 mg/kg intravenous infusion every 4 weeks, may increase to 8 mg/kg every 4 weeks if necessary, maximum 800 mg/dose; body weight <100 kg: 162 mg subcutaneously every 2 weeks initially, increase to 162 mg once weekly if necessary; body weight ≥100 kg: 162 mg subcutaneously once weekly
OR
sarilumab: 200 mg subcutaneously every 2 weeks
MoreOR
tofacitinib: 5 mg orally (immediate-release) twice daily; 11 mg orally (extended-release) once daily
OR
baricitinib: 2 mg orally once daily
OR
upadacitinib: 15 mg orally once daily
OR
filgotinib: 100-200 mg orally once daily
methotrexate
Combination therapy with methotrexate and either a biological agent or a targeted synthetic disease-modifying anti-rheumatic drug (DMARD) is recommended first line in these patients.[49][88]
For patients taking weekly oral methotrexate who are not at target, switching to subcutaneous methotrexate is recommended over addition of/switching to alternative DMARD(s).[49]
Folic acid supplementation can also be started at the same time as starting methotrexate, as a prophylactic measure to reduce the risk of some adverse effects.
[ ]
Primary options
methotrexate: 7.5 mg orally/subcutaneously once weekly (on the same day each week) initially, increase gradually according to response, maximum 20 mg/week
biological agent or disease-modifying anti-rheumatic drug (DMARD)
Treatment recommended for ALL patients in selected patient group
TNF-alpha inhibitors (etanercept, infliximab, adalimumab, certolizumab pegol, and golimumab) all have proven efficacy in placebo-controlled trials.[110][111]
[ ]
One systematic review and network meta-analysis reported only minor differences in efficacy between biological treatments in combination with methotrexate in patients with rheumatoid arthritis (RA) after methotrexate failure.[167]
One network meta-analysis reported that biological agents in combination with methotrexate (with the exception of golimumab) were associated with significantly lower rates of radiographic progression at 1 year compared with methotrexate alone.[112]
TNF-alpha inhibitors are approved for use either with or without methotrexate depending on the specific drug; check local drug formulary for specific licence information.
TNF-alpha inhibitors have been associated with increased risk for serious infection (tuberculosis and other opportunistic infections) compared with synthetic DMARDs, and increased risk for treatment discontinuation.[115][116]
[ ]
[ ]
However, systematic reviews and meta-analyses have not reported an increased risk of malignancy among patients with RA receiving TNF-alpha inhibitor therapy.[116][117][118][119][120][121] Ongoing research seeks to establish the effect of specific DMARDs on risk of malignancy, particularly risk for non-melanoma skin cancer and melanoma.[122]
Potential adverse effects associated with TNF-alpha inhibitors could be minimised by using an individualised dose reduction/withdrawal strategy once disease control has been established.
The results of two systematic reviews suggest that disease activity-guided dose tapering of TNF-alpha inhibitors is comparable to continuation of treatment with respect to the proportion of patients with persistent remission and may be comparable regarding disease activity, while discontinuation of TNF-alpha inhibitors is inferior to continuation of treatment with respect to disease activity, the proportion of participants with persistent remission, function, and minimal radiographic damage.[123][124]
Abatacept is a T-cell modulator approved for the treatment of moderately to severely active RA. It has similar safety and efficacy to the TNF-alpha inhibitors, and is indicated in patients who have an inadequate response to methotrexate.[138][139]
[ ]
Abatacept or adalimumab given subcutaneously with background methotrexate (as would usually be the case in clinical practice) were shown to have similar efficacy, safety, and time to response in patients with active RA who were naive to biological agents and who had an inadequate response to methotrexate.[139]
Evidence suggests that abatacept, as monotherapy or in combination with methotrexate, provides more effective disease control compared with conventional treatment (methotrexate with corticosteroids), methotrexate alone, biological agents or targeted synthetic DMARDs in patients with RA.[140][141][142]
[ ]
There is evidence demonstrating sustained remission with abatacept following dose reduction or complete drug withdrawal.[141][143] Few patients sustain a major response 1 year after withdrawal of abatacept therapy; re-treatment with abatacept plus methotrexate may be effective in this setting.[144]
Abatacept is recommended over other biological agents and targeted synthetic DMARDs for patients with non-tuberculous mycobacterial lung disease who have moderate-to-high disease activity despite conventional synthetic DMARDs.[49]
Rituximab is a B-cell modulator approved for use in combination with methotrexate for the treatment of adults with moderately to severely active RA who have had an inadequate response to one or more TNF-alpha inhibitors.[49]
Rituximab is recommended over other DMARDs, regardless of previous DMARD experience, for patients who have a previous lymphoproliferative disorder (for which rituximab is an approved treatment), and who have moderate-to-high disease activity, because it would not be expected to increase the risk of recurrence or worsening of lymphoproliferative disorders.[49]
In the setting of persistent hypogammaglobulinaemia without infection, continuation of rituximab therapy for patients at target is conditionally recommended over switching to a different biological agent or targeted synthetic DMARD.[49] Continuing rituximab in patients who are at target is preferred due to the uncertain clinical significance of hypogammaglobulinaemia in patients without infection. Although an increased risk of infection has been described in RA patients with hypogammaglobulinaemia, it is not known if a switch in DMARDs in patients who are at target is more effective in lowering infection risk while maintaining disease control than continuation of rituximab.
Interleukin 6 (IL-6) inhibitors (tocilizumab and sarilumab) are approved for the treatment of adults with moderately to severely active RA who have had an inadequate response to one or more DMARDs. They may be used as monotherapy, or in combination with methotrexate or other conventional synthetic DMARDs.[125][126][127]
Evidence from systematic reviews using indirect comparisons suggest that tocilizumab may be more effective than sarilumab for treating people with RA who inadequately respond to either methotrexate or TNF-alpha inhibitors.[128][129] An additional systematic review concluded that for people with RA with an inadequate response to conventional synthetic DMARDs, sarilumab monotherapy is more effective than adalimumab, biological agents and targeted synthetic DMARDs.[130]
One open-label randomised trial evaluated the efficacy and safety of increasing the dose interval of subcutaneous tocilizumab in patients with RA who are in remission.[131] The study reported that although most patients sustained remission with a half-dose of tocilizumab, increasing the dose interval to 2 weeks was associated with a lower likelihood of maintaining remission, with no improvement in tolerability.[131]
There is evidence to suggest that treatment with IL-6 inhibitors may increase risk of serious infection, opportunistic infections, and cancer in patients with RA compared with placebo.[132] Tocilizumab has been associated with a drug-induced sarcoidosis-like reaction, occurring in temporal relationship with the initiation of tocilizumab, and a significant risk of the reactivation of hepatitis B virus (HBV) in people with RA and chronic HBV.[132][133][134][135]
The European Medicines Agency (EMA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA) identified serious hepatotoxicity (including acute liver failure, hepatitis, and jaundice) in eight patients treated with tocilizumab worldwide.[136][137] Monitor alanine aminotransferase (ALT) or aspartate aminotransferase (AST) at initiation of treatment, every 4-8 weeks for the first 6 months of treatment, and then every 12 weeks thereafter.[136][137] Advise patients to seek medical help immediately if they experience signs and symptoms of hepatic injury.[137]
Targeted synthetic DMARDs include the oral Janus kinase 1-selective (JAK1) inhibitors tofacitinib, baricitinib, and upadacitinib, which are all approved to treat moderate to highly active RA.[49][150] Filgotinib, another selective inhibitor of JAK1, is approved in Europe and the UK for the treatment of moderate to severely active rheumatoid arthritis in adults who have responded inadequately to, or who are intolerant to, one or more DMARDs.
The US Food and Drug Administration (FDA) has issued a warning about an increased risk of serious cardiovascular events, malignancy, thrombosis, and death with tofacitinib, baricitinib, and upadacitinib.[145] This follows final results from a large randomised safety clinical trial comparing tofacitinib with tumour necrosis factor (TNF)-alpha inhibitors in patients with RA. The study found an increased risk of blood clots and death with the lower dose of tofacitinib (5 mg twice daily); this serious event had previously been reported only with the higher dose (10 mg twice daily) in the preliminary analysis.[146]
The FDA advises clinicians to reserve tofacitinib, baricitinib, and upadacitinib for patients who have an inadequate response or are intolerant to one or more TNF-alpha inhibitors, and to consider the patient's individual benefit-risk profile when deciding to prescribe or continue treatment with these medications, particularly in patients who are current or past smokers, patients with other cardiovascular risk factors, those who develop a malignancy, and those with a known malignancy (other than a successfully treated non-melanoma skin cancer).[145]
The European Medicines Agency (EMA) has also recommended measures to minimise the risk of serious adverse effects with JAK inhibitors. The EMA advice relates to patients aged >65 years, those who are current or past smokers, patients with other cardiovascular risk factors (such as heart attack or stroke), and patients with other malignancy risk factors. In these patient groups, JAK inhibitors should only be used to treat moderate or highly active RA, if no suitable treatment alternative is available.[147]
The EMA recommends that JAK inhibitors should be used with caution in patients with risk factors for blood clots in the lungs and in deep veins (venous thromboembolism, VTE); and that doses should be reduced in patient groups who are at risk of VTE, cancer, or major cardiovascular problems, if possible. This recommendation is based on one observational study comparing the safety of baricitinib with TNF-alpha inhibitors.[147][148]
In the UK, the National Institute for Health and Care Excellence (NICE) has recommended filgotinib (a JAK1 inhibitor) in combination with methotrexate as an option for adult patients with moderate to severe RA (i.e., a disease activity score [DAS28] of 3.2 or more), who have an inadequate response to intensive therapy with two or more conventional synthetic DMARDs.[149]
For patients with severe disease (DAS28 of more than 5.1) NICE recommends filgotinib with methotrexate as an option if the patient cannot tolerate rituximab and has responded inadequately to or cannot have other DMARDs, including at least one biological DMARD, or has had an inadequate response to rituximab and at least one biological DMARD.[149]
Filgotinib can be used as monotherapy in a patient with a contraindication to or intolerance of methotrexate when the above criteria are met.[149][150]
For patients at target for at least 6 months, the preferred option is to continue all DMARDs at their current dose, rather than reducing the dose or gradual discontinuation of DMARD treatment.[49]
For patients taking combination therapy who wish to discontinue a DMARD, gradual discontinuation of methotrexate is recommended rather than gradual discontinuation of the biological agent or targeted synthetic DMARD.[49][90] One open-label randomised controlled trial comparing half-dose with stable conventional synthetic DMARDs found that patients given the half-dose had significantly more disease flares than those on the stable dose.[91]
Primary options
etanercept: 50 mg subcutaneously once weekly; or 25 mg subcutaneously twice weekly
OR
infliximab: 3 mg/kg intravenous infusion at weeks 0, 2, 6, and then every 8 weeks thereafter
MoreOR
adalimumab: 40 mg subcutaneously every 2 weeks
OR
certolizumab pegol: 400 mg subcutaneously at weeks 0, 2, and 4, and then 200 mg every 2 weeks or 400 mg every 4 weeks thereafter
OR
golimumab: 50 mg subcutaneously once monthly; or 2 mg/kg intravenous infusion at weeks 0 and 4, and then every 8 weeks thereafter
OR
abatacept: body weight <60 kg: 500 mg intravenous infusion at weeks 0, 2, and 4, and then every 4 weeks thereafter; body weight 60-100 kg: 750 mg intravenous infusion at weeks 0, 2, and 4, and then every 4 weeks thereafter; body weight >100 kg: 1000 mg intravenous infusion at weeks 0, 2, and 4, and then every 4 weeks thereafter
MoreOR
rituximab: 1000 mg intravenous infusion on days 1 and 15, may repeat course every 16-24 weeks if inadequate response
OR
tocilizumab: 4 mg/kg intravenous infusion every 4 weeks, may increase to 8 mg/kg every 4 weeks if necessary, maximum 800 mg/dose; body weight <100 kg: 162 mg subcutaneously every 2 weeks initially, increase to 162 mg once weekly if necessary; body weight ≥100 kg: 162 mg subcutaneously once weekly
OR
sarilumab: 200 mg subcutaneously every 2 weeks
MoreOR
tofacitinib: 5 mg orally (immediate-release) twice daily; 11 mg orally (extended-release) once daily
OR
baricitinib: 2 mg orally once daily
OR
upadacitinib: 15 mg orally once daily
OR
filgotinib: 100-200 mg orally once daily
Choose a patient group to see our recommendations
Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer
Use of this content is subject to our disclaimer