Rheumatology
Article8 min read
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Since the introduction of biologic disease-modifying antirheumatic drugs (bDMARDs), clinical remission has become an achievable therapeutic goal for many patients with chronic rheumatic diseases.1-3

bDMARDs have mechanisms of action (MoAs) that inhibit specific targets involved in disease pathogenesis.1,4 These MoAs are underlaid by differing molecular structures of bDMARDs which impact how these treatments interact with immune pathways.1,4,5

Examples of different bDMARD structures1,a

The molecular structure of a bDMARD can affect various immune processes that may underlie its function.5-7 For example, rheumatoid factors (RFs) can bind to fragment crystallisable (Fc)-containing bDMARDs, impacting their function.5,7-9 The structure of Fc-containing bDMARDs also allows them to cross the placenta, thereby potentially disrupting treatment continuity for women of childbearing age.10-12

Read on to find out more about the impact of the molecular structure of Fc-containing bDMARDs.

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RHEUMATOID FACTOR 01

Immune complex formation

2 MIN READ

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IMMUNE COMPLEX FORMATION

How does RF form immune 

complexes?

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IMMUNE COMPLEX FORMATION

Where do RF-IgG immune 

complexes end up?

Large RF-IgG immune complexes can be internalised, predominantly by macrophages through the Fc-gamma receptors (FcγRs) on their cell surface and are subsequently degraded by lysosomes.9,26 This activation of the immune system to degrade RF-IgG immune complexes attracts additional immune cells to the affected joints, thereby further increasing inflammation.8 

High RF levels are associated with a decreased response to anti-TNFs containing an Fc region.17,19,20,b

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Many bDMARDs used in RA 

contain Fc regions27,28

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How could RF-IgG immune complexes be impacting the treatment response of your patients with RA?

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RHEUMATOID FACTOR 02

Clinical implications of bDMARD structure: The case of RF

2 MIN READ

High RF levels are recognised as a poor prognostic factor for RA and a predictor of responses to treatment.18-20,22 Prof. James Galloway explores how the binding of RF to the Fc region of antibodies can affect clearance of some Fc-containing biologics, which could have implications for treatment choice.7,8

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“Rheumatoid factor can bind and form immune complexes with drugs that have an Fc component”

Prof. James Galloway

King’s College London, London, United Kingdom

PLACENTAL TRANSFER 02

Fc structure and its potential implications for
placental transfer

2 MIN READ

Early and continuous treatment to achieve remission is recommended for women of childbearing age (18–45 years) with chronic rheumatic diseases.12,29-31 This approach helps to prevent disease progression, maintain quality of life and support future family plans.29,31-34 However, Fc-containing anti-TNFs can cross the placenta, which may necessitate further treatment-planning discussions and disrupt treatment continuity.10-12

In the video below, Dr Pluma shares her expert insights on the potential impact of placental transfer of Fc-containing bDMARDs, and how this might impact treatment planning for women of childbearing age.

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“It is important to take into account both drug effectiveness and placental transfer with regards to biologic treatments used during pregnancy"   

Dr. Andrea Pluma Sanjurjo

Vall d'Hebron University Hospital, Barcelona, Spain

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GL-DA-2500784

Date of preparation: October 2025

Footnotes

a) Visual image does not imply comparable safety profile, efficacy or indication. 

b) High RF level cutoffs are defined as >160 IU/mL or >200 IU/mL in different studies. The >160 IU/mL cutoff is based on RF levels quartile 4 (Q4) from the ANSWER observational study in Japanese adult patients with RA (177 patients in the Q4 >166 IU/mL) and the >200 IU/mL cutoff is based on Q4 from a post-hoc analysis of the EXXELERATE phase 4 study (NCT01500278) in adult patients with RA (n=226) Q4 >204.0 IU/mL as well as the Q4 from a post-hoc analysis that included data from pooled RAPID trials Q4 ≥207.0 IU/mL (RAPID-1 [NCT00152386], RAPID-2 [NCT00160602], J-RAPID [NCT00791999], RAPID-C [NCT02151851]), and EXXELERATE (NCT01500278) Q4 >204.0 IU/mL. Overall, 1,537 and 908 patients were included in pooled RAPID trials and EXXELERATE, respectively. Patients were classified into equal quartiles according to baseline RF. Patient demographics and baseline disease characteristics were similar between groups and across RF quartiles.7,35,36

References

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Abbreviations

bDMARD: Biologic disease-modifying antirheumatic drug; EULAR: European Alliance of Associations for Rheumatology; Fc: Fragment crystallisable; FcγR: Fc-gamma receptor;
Ig: Immunoglobulin; MoA: Mechanism of action; PEG: Polyethylene glycol; Q: Quartile; RA: Rheumatoid arthritis; RF: Rheumatoid factor; TNF: Tumour necrosis factor.