Rheumatoid arthritis: previously untreated early disease

Overview

General background | Focus of the review | Comments on evidence | Search and appraisal summary | Substantive changes at this update | Abstract | Cite as

Top

General background

Rheumatoid arthritis is a chronic autoimmune disease, which most often presents as a symmetrical polyarthritis of the hands and feet. The symptoms of episodic joint pain and stiffness are exacerbated by rest and improved by movement. There is associated swelling and warmth of the affected joints due to inflammation of the synovium (synovitis). Treatments are classified as non-steroidal anti-inflammatory drugs (NSAIDs, such as ibuprofen), glucocorticoids (GCs, such as prednisolone or prednisone, which are biologically equivalent) and other disease-modifying anti-rheumatoid drugs, so called because they reduce the acute phase response and radiological joint damage (DMARDs, such as methotrexate and intramuscular gold). Recommendations regarding the treatment of newly diagnosed rheumatoid arthritis have changed frequently over the last 20 years; as new therapeutic agents have emerged, old ones have been re-evaluated and new evidence has accumulated. Methotrexate has become the most widely prescribed DMARD, and the UK National Institute for Health and Care Excellence (NICE) has recommended a combination of DMARDs (including methotrexate and at least one other DMARD, plus short-term glucocorticoids) as first-line treatment.[1] In routine clinical practice, many patients are treated with many different individual and combination therapies. Biological DMARDs, developed over the last 15 years, are (generally) specially prepared antibodies derived from biological processes. This and other drug developments have resulted in a nomenclature system for these drugs[2] that has been used in this overview as follows: DMARDs are synthetic (that is, small chemical molecules; sDMARDs) or biological (usually modified antibodies; bDMARDs). Synthetic DMARDs are either conventional (that is, their precise mode of action is not known and they have been in use for many years; csDMARDs) or targeted (that is they were developed to target a specific cellular activity; tsDMARDs). Biological DMARDs are original (that is, developed specifically under particular conditions; boDMARDs) or 'biosimilar' (that is, developed to be similar to a boDMARD but not necessarily under the same conditions; bsDMARDs).

Top

Focus of the review

The past two decades have shed light on the extent of irreversible joint damage occurring in the early stages of rheumatoid arthritis,[3][4] but most of the clinical trials of newly developed agents, especially bDMARDs, have been in patients with longer-term disease in whom other treatments have failed to control symptoms. Therefore, this overview examines the evidence for the best first-line treatment for early rheumatoid arthritis. We focus on treatment-naïve patients to allow generalisability to the population of newly diagnosed patients.

Top

Comments on evidence

All the trial data reported in this overview were gathered from participants who met (or are extremely likely to have met) the 1987 American Rheumatism Association (ARA; now the American College of Rheumatology [ACR]) criteria for rheumatoid arthritis, and all had current signs of active disease (defined in a variety of ways in different studies). The trial data were also taken from patients who had not been previously treated with csDMARDs (for >1 month) or bDMARDs. The overview results are, therefore, generalisable to the initiation of first-line treatment in people with newly diagnosed rheumatoid arthritis who fulfil the ARA 1987 criteria. Some studies excluded people who were thought to be at risk of certain adverse events or who had certain comorbidities, but many did not do so.

Top

Search and appraisal summary

The literature search for this overview was carried out from the start of each database searched up to December 2014. For more information on the electronic databases searched and criteria applied during assessment of studies for potential relevance to the overview, please see the Methods section. Searching of electronic databases retrieved 2058 studies. Of the full articles evaluated, 10 systematic reviews, 22 RCTs, and one follow-up report were added at this update.

Top

Substantive changes at this update

Methotrexate plus other csDMARD therapy versus methotrexate monotherapy New option. Six systematic reviews[26][27][28][29][30][31] and eight RCTs added.[32][33][34][35][36][37][38][39] Categorised as 'unlikely to be beneficial'.

Abatacept monotherapy New option. No evidence found. Categorised as 'unknown effectiveness'.

Anakinra monotherapy New option. No evidence found. Categorised as 'unknown effectiveness'.

Certolizumab monotherapy New option. No evidence found. Categorised as 'unknown effectiveness'.

Infliximab monotherapy New option. No evidence found. Categorised as 'unknown effectiveness'.

Rituximab monotherapy New option. No evidence found. Categorised as 'unknown effectiveness'.

Tofacitinib monotherapy New option. No evidence found. Categorised as 'unknown effectiveness'.

Adalimumab monotherapy New option. No evidence found. Categorised as 'unknown effectiveness'.

Etanercept monotherapy New option. No evidence found. Categorised as 'unknown effectiveness'.

Golimumab monotherapy New option. No evidence found. Categorised as 'unknown effectiveness'.

Tocilizumab monotherapy New option. No evidence found. Categorised as 'unknown effectiveness'.

Abatacept plus methotrexate New option. No evidence found. Categorised as 'unknown effectiveness'.

Anakinra plus methotrexate New option. No evidence found. Categorised as 'unknown effectiveness'.

Certolizumab plus methotrexate New option. No evidence found. Categorised as 'unknown effectiveness'.

Tofacitinib plus methotrexate New option. No evidence found. Categorised as 'unknown effectiveness'.

Adalimumab plus methotrexate New option. Three RCTs added.[45][46][47] Categorised as 'likely to be beneficial'.

Etanercept plus methotrexate New option. One RCT added.[50] Categorised as 'likely to be beneficial'.

Golimumab plus methotrexate New option. No evidence found. Categorised as 'unknown effectiveness'.

Infliximab plus methotrexate New option. One RCT added.[52] Categorised as 'trade off between benefits and harms'.

Rituximab plus methotrexate New option. No evidence found. Categorised as 'unknown effectiveness'.

Tocilizumab plus methotrexate New option. No evidence found. Categorised as 'unknown effectiveness'.

Glucocorticoids plus methotrexate or other csDMARD (or combination of csDMARDs) versus methotrexate or other csDMARD (or combination of csDMARDs) New option. Six systematic reviews[27][29][58][59][60][61] 12 RCTs,[55][62][63][64][65][66][67][68][69][70][71][72] and one follow-up report added.[73] Categorised as 'beneficial'.

Abstract

INTRODUCTION: Rheumatoid arthritis is a chronic autoimmune disease, which most often presents as a symmetrical polyarthritis of the hands and feet. Pharmacological treatments include non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids (GCs) and other disease-modifying anti-rheumatoid drugs (DMARDs), which may be synthetic (either conventional [csDMARDs] or targeted [tsDMARDs]) or biological (bDMARDs). METHODS AND OUTCOMES: We conducted a systematic overview, aiming to answer the following clinical questions: What are the effects of methotrexate in combination with other csDMARDs versus methotrexate monotherapy in people with rheumatoid arthritis who have not previously received any DMARD treatment (first-line treatment)? What are the effects of bDMARDs as monotherapy versus methotrexate or other csDMARDs in people with rheumatoid arthritis who have not previously received any DMARD treatment (first-line treatment)? What are the effects of bDMARDs in combination with methotrexate versus methotrexate monotherapy or other csDMARDs in people with rheumatoid arthritis who have not previously received any DMARD treatment (first-line treatment)? What are the effects of glucocorticoids in combination with methotrexate or with other csDMARDs versus methotrexate or other csDMARDs in people with rheumatoid arthritis who have not previously received any DMARD treatment (first-line treatment)? We searched: Medline, Embase, The Cochrane Library and other important databases up to December 2014 (BMJ Clinical Evidence overviews are updated periodically; please check our website for the most up-to-date version of this overview). RESULTS: At this update, searching of electronic databases retrieved 2058 studies. Of the full articles evaluated, 10 systematic reviews, 22 RCTs, and one follow-up report were added at this update. We performed a GRADE evaluation for 18 PICO combinations. CONCLUSIONS: In this systematic overview, we categorised the efficacy for 22 comparisons based on information about the effectiveness and safety of bDMARDs (monotherapy or combined with csDMARDs), csDMARDs (monotherapy or combined with other csDMARDs), glucocorticoids combined with methotrexate or other csDMARDs, and methotrexate (monotherapy or combined with other csDMARDs), identifying interventions which were likely or unlikely to be beneficial.

Cite as

Gunasekera WMA, Kirwan JR. Rheumatoid arthritis: previously untreated early disease. Systematic review 1124. BMJ Clinical Evidence. . 2016 August. Accessed [date].