Clinical Focus
Therapy Update
Rheumatoid arthritis : the game-changers
Rheumatology
Dr Mansi Bhurani ( left ) is a basic physician trainee at Alfred Health , Melbourne , Victoria .
Associate Professor Andrew Östör ( right ) is a consultant rheumatologist at Cabrini Health , Melbourne ; principal investigator at Emeritus Research , Melbourne ; and Associate Professor in the department of medicine at Monash University , Melbourne , Victoria and ANU medical school , Canberra , ACT .
Biologics have revolutionised treatment and their safety profile remains favourable given the therapeutic benefit of reduced disease activity .
RHEUMATOID arthritis is a chronic multisystem autoimmune disease with significant potential impacts on quality of life and function .
However , over the last two decades the outcomes with rheumatoid arthritis ( RA ) have improved dramatically , in part due to treatment with biologic disease modifying antirheumatic drugs ( bDMARDs ). Methotrexate and other conventional synthetic DMARDs remain first-line therapy for patients with moderate to severe disease . However , their limited efficacy and side effect profile , including gastrointestinal upset and potential for liver toxicity and haematological changes , necessitated establishment of further therapies for RA . 1 Thus bDMARDs and targeted synthetic DMARDs were developed and have now altered the entire therapeutic landscape . 2 As a consequence , unprecedented improvements have been seen in the signs and symptoms of disease , patient reported outcomes and radiographic damage . Currently the goal of management is remission , a concept that was unimaginable 20 years ago .
Given the increasingly important role of bDMARDs in managing RA , it is essential that clinicians are aware of these agents and their well characterised adverse effect profiles . This article will focus on the key side effects of which to be mindful , and also highlight the critical role of primary care in monitoring patients with RA who require these advanced therapies .
Biologic DMARD classes
Biologic DMARDs for RA can be broadly categorised into inhibitors of TNF ( anti-TNF ), interleukin-6 ( IL-6 ), T-cell co-stimulation and B-cell CD20 depleting antibodies ( see table 1 ). All are generally well tolerated by the majority of patients . The most common adverse effect shared by these agents is an increased risk of infection , both serious and opportunistic . 3 Contrary to initial reports , newer trials have been reassuring in relation to the overall risk of malignancy including lymphoma and major cardiovascular events . 4
TNF inhibitors ( TNF-i ) These agents are directed against the TNF
Over the last two decades the outcomes with rheumatoid arthritis have improved dramatically . molecule responsible for inflammation in many patients with RA . There are a variety of agents with differing features , although the overall adverse event profile is similar . Certolizumab is a pegylated fragment of the TNFi antibody . This means it does not cross the placenta and is absent in breastmilk and thus represents an advantage as a treatment option in women of child-bearing potential . 5 In fact , evidence has accumulated that all anti-TNF agents are likely safe during pregnancy . 5
NEED TO KNOW
The main adverse effect of biologic disease modifying antirheumatic drugs ( bDMARDs ) is an increased risk of infections , both serious and opportunistic .
Tocilizumab carries a slight increased risk of localised intestinal perforation .
Screening for infections such as latent TB , HIV , and hepatitis B and C , is undertaken prior to commencing treatment .
Advise patients to continue with routine national cancer screening programs and vaccination schedules , but to avoid live vaccines .
Biologics should be discontinued if infection develops but can be recommenced once treated .
The common adverse effect profile with these agents includes an increased risk of infection particularly URTIs and UTIs . Rarer events , including LFT derangement , drug induced lupus ,
Table 1 : Biologic DMARD classes , side effects and contraindications Drug class Side effects Contraindications TNF inhibitors
Adalimumab 40mg SC fortnightly
Certolizumab 200mg SC fortnightly
Etanercept 50mg SC weekly Golimumab 50mg SC monthly Infliximab 3-10mg / kg 8 weekly Interleukin-6 ( IL-6 ) inhibitors
Tocilizumab 162mg SC weekly or 8mg / kg IV monthly
CD20 depleting antibodies
Rituximab IV two course dose , repeat after > 6 months
Increased risk of infection , rarer LFT derangement , drug induced lupus , psoriasis and injection site reactions
Infections , injection site reactions , hypersensitivity reactions , lower intestinal perforation , LFT derangements , hyperlipidaemia , neutropenia
Infections , hypersensitivity reactions , cytopenias , hepatitis B reactivation , progressive multifocal leukoencephalopathy
Serious or untreated infections , recent malignancy , demyelinating diseases , hypersensitivity , New York Heart Association III-IV heart failure
Serious or untreated infections , hypersensitivity , diverticulitis
Serious or untreated infections , hepatitis B
T-cell ( CD80 / 86 ) co-stimulation inhibitors
Abatacept 125mg SC weekly or IV infusion
Infection , hypersensitivity reactions , infusion reactions , leukopenia
Serious or untreated infections , recent malignancy
First published online on 12 May 2023
Biosimilars Similar reactions , efficacy and safety as their analogues