Fatigue prevalent and persistent in patients with early RA

Fatigue is prevalent and remains stable in patients with early rheumatoid arthritis (RA) even when there is an improvement in inflammatory disease activity, according to research published in Rheumatology.

Researchers including Professor David Andrew Walsh, a Consultant Rheumatologist at Sherwood Forest Hospitals NHS Foundation Trust, analysed data from the Early Rheumatoid Arthritis Network (ERAN), a multicentre inception cohort of UK RA patients.

They found that age and sex standardised prevalence rates of fatigue and severe fatigue in the cohort (1,236) were 44% and 19%, respectively. Furthermore, fatigue “changed little” over a study period of 3 years in which measurements were taken 5 times.

The researchers also linked female sex, worse pain, mental health and functional ability with greater fatigue, but found no significant association with swollen joint count and erythrocyte sedimentation rate.

They concluded that given the diverse baseline characteristics of the patients in the cohort, it is likely that central mechanisms are linked with persistent fatigue in patients with RA. Thus, “management of fatigue might require complex interventions targeted at central mechanisms in addition to disease modification, and people who require such interventions might be identified at presentation with early RA,” they said.

Higher risk of herpes zoster in RA patients taking ts/bDMARDs

New research has found that patients with rheumatoid arthritis (RA) taking targeted synthetic (ts)DMARDs have a 3.6-fold increased risk of developing herpes zoster (HZ), and that there is also a significantly higher risk associated with biologic (b)DMARDs versus conventional synthetic (cs)DMARDs.

For the study, published in the British Medical Journal, Researchers compared the incidence rates and risk of HZ in 13,991 patients with RA who were under treatment with different acting DMARDs within the German Rheumatoid Arthritis: Observation of biologic therapy register RABBIT.

The data showed 559 HZ events in 533 patients, with the highest exposure-adjusted event rate (EAER) in patients taking tsDMARDs (21.5), followed by B cell targeted therapy (10.3), monoclonal anti-TNF antibodies (9.3), interleukin 6 inhibitors (8.8), soluble TNF receptor fusion protein (8.6), T cell costimulation modulator (8.4) and csDMARDs (7.1).

When adjusted for age, sex and glucocorticoids and inverse probability weighting, tsDMARDs (HR 3.66), monoclonal anti-TNF antibodies (HR 1.63) and B cell targeted therapy (HR 1.57) “showed a significantly higher risk compared with csDMARDs,” the authors noted. Higher age and glucocorticoids (3.5-fold higher risk at doses above 10 mg) were also linked with a greater risk of HZ.

As such, the authors concluded that “an increased risk of HZ should be considered especially under JAK inhibitors, in elderly patients, and under glucocorticoid therapy”. Such patients should be considered for HZ vaccination, they added, and noted that preliminary data from tofacitinib-treated patients with RA indicate the possibility of reducing the risk of HZ by vaccination, they noted.

Slower B cell reconstitution and lower vaccine response in rheumatology patients

Researchers have found that B cell reconstitution following post-therapy depletion was much slower in rheumatology patients than in those with an underlying haematological condition, and that this was linked to reduced COVID-19 responsiveness.

The team, which included Dr Srinivasan Venkatachalam, a Consultant Rheumatologist at the Royal Wolverhampton NHS Trust, assessed serological responsiveness to SARS-CoV-2 vaccines after a second dose in 38 patients with underlying rheumatological disease and 80 patients with underlying haematological malignancy previously treated with anti-CD20 B cell depleting agents.

The findings, presented at the 63rd American Society of Hematology (ASH) Annual Meeting and Exposition, showed that just 22% of rheumatology patients versus 78% of haematology patients achieved a normal B cell count 7-12 months after B cell depletion therapy.

In both patient populations it was found that vaccine non-responders had significantly smaller populations of peripheral CD19+ B cells – 0.07 vs 0.01 x109/L for rheumatology patients versus 0.20 vs 0.02 x109/L for haematology patients.

Also, response to the vaccine was found to be lower in the first 6 months immediately after B cell depletion therapy – 33.3% in the rheumatology arm versus 42.9% in the haematology cohort – rising to 75% and 100%, respectively, in those who received a second dose six to twelve months after B cell depletion.