Tumor necrosis factor inhibitors (TNFi or anti-TNFs) have significantly contributed
in improving the clinical outcomes of rheumatoid arthritis (RA), however,
safety has always been a concern.
The study
confirms and expands the known safety profile of Adalimumab and reports no
additional safety risk of laboratory abnormalities, hepatitis B reactivation and
pregnancy outcomes.
Tumor necrosis factor inhibitors (TNFi or anti-TNFs) have significantly contributed in improving the clinical outcomes of rheumatoid arthritis (RA), however, safety has always been a concern. Various severe infectious event (SIE) have been reported in patients using biologics. Different risk minimization activities, such as vaccinations and latent tuberculosis (TB) infection (LTBI) screening and prophylaxis are used to mitigate the infection risk. Recently, many other adverse events (AEs) have become a focus of interest including viral reactivation, vaccination response, laboratory abnormalities and pregnancy outcomes. This study focused on above-emerging events using comprehensive data from global Adalimumab clinical trials in RA.
Rationale behind the research:
This research has been carried out to account for adverse effects, and safety concerns associated with anti-TNF use in RA patients.
Objective:
To update adverse events (AEs) of particular interest from global Adalimumab clinical trials in RA patients.
Study outcomes:
Time Points: Baseline and 6 months
Outcomes
Baseline: No significant baseline differences were observed between the groups.
Study outcomes:
Fig 1: Incidence rates of serious infections in women patients with RA (Events/ 100 patient years)
Fig 2: Incidence rates of major birth defects in pregnant women with RA exposed to adalimumab
Fig 3: Pregnancy outcome (live birth rates) associated with adalimumab exposure in pregnant women with RA
Anti-TNF therapy has always been a
matter of concern as they are associated with an increased risk of infections.
The spectrum of infections reported in this study possess similarity with those
reported with other anti-TNFs in both randomized clinical trials and
registries. There is no change found in the types of infections over a period.
The opportunistic infections include
a variety of possible bacterial, mycobacterial, fungal, viral and parasitic
agents which may be challenging from a diagnostic perspective. Recently, there
has been a considerable interest in herpes zoster infections. The overall rate of
HZ with Adalimumab was low and similar to reported rates in registries and a
large claims database. It is suggested that anti-TNF
therapies usage may not put patients at higher risk of HZ. However, still there
is a need of the risk-benefit assessment for vaccination before starting biological
therapy.
Overall, the impact of Adalimumab on haemoglobin and lipid parameters
implicated no new safety signals about MTX-monotherapy, in both early and
long-standing RA. There is a great importance of
monitoring lipid changes owing to the probability of an increased risk of
cardiovascular events in RA. It is recommended that RA patients should be
vaccinated with non-live agents, even if their treatment with anti-TNF therapy
is ongoing.
However, awareness of vaccination among RA patients
appears to be low, since only a minority of patients with RA starting Adalimumab
receive influenza vaccination. Patients who received this vaccine were
presented with fewer influenza-related adverse effects over an average of
5.6 years of follow-up, compared with patients not receiving the vaccine.
Like other anti-TNFs, Adalimumab is
classified as pregnancy category B (no documented human toxicity) by the US
Food and Drug Administration. The safety of Adalimumab in pregnancy has been
reported in a reproductive animal study. The animal study has revealed no
evidence of fetal harm on administration with Adalimumab,
but only a small number of Adalimumab-exposed human pregnancies have been
published to date. The OTIS registry reported neither specific pattern of
defects in Adalimumab-exposed infants during prenatal development nor adverse
pregnancy outcomes.
Annals of the Rheumatic Diseases 2017; 76:414-417.
Adalimumab long-term safety: infections, vaccination response and pregnancy outcomes in patients with rheumatoid arthritis
Burmester GR et al.
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