Rheumatic diseases associated with reproductive issues and adverse pregnancy outcomes, study finds

26th March 2024

Rheumatic diseases can have a wide-ranging impact on men’s and women’s reproductive health, with effects comparable to other immune-mediated conditions, a Finnish study finds.

It was known that immune-mediated diseases (IMDs) could impair reproductive success and pregnancy outcomes, but systematic evaluations across diseases were lacking, Finnish, US and UK researchers wrote in the journal Rheumatology.

Using Finnish registry data comprising 5,339,804 citizens, individuals born from 1964 to 1984 and diagnosed with any one of 19 IMDs before age 30 (women) and 35 (men) were matched with 20 controls by birth year, sex and education.

Researchers then analysed the impact of rheumatic diseases compared with other IMDs on reproductive health measures, such as reproductive success and, for women, adverse maternal and perinatal outcomes.

‘Overall, we observed a high variability in the prevalence of childlessness and the number of children between diseases, as well as high variability in the impact of individual diseases,’ the researchers reported.

On average, women with IMDs experienced a higher prevalence of childlessness than controls (mean difference 3.6%), with women with Addison’s disease experiencing 23.9% more childlessness, those with juvenile idiopathic arthritis (JIA) 9.3% more childlessness, and those with vitamin B12 deficiency anaemia experiencing 8.6% more childlessness.

Men with an IMD also had a higher prevalence of childlessness than controls (mean difference 4.7%).

In men, most diseases made no difference to childlessness rates, but the three conditions found to have the most impact were myasthenia gravis (20.1% more childlessness), Addison’s disease (16.4% more childlessness), and vitamin B12 deficiency anaemia (13.7% more childlessness).

Several of the rheumatic diseases, particularly systemic lupus erythematosus (SLE), JIA, and seropositive rheumatoid arthritis, were associated with higher rates of childlessness and fewer children in both men and women.

‘IMDs such as psoriatic disease, asthma, alopecia areata, coeliac disease, and [immune thrombocytopenia] ITP, were not associated with an increased prevalence of childlessness or reduced number of children in either sex, although some had higher use of assisted reproductive technology,’ the researchers noted.

“Inflammatory bowel disease (IBD) was not, in contrast to the findings of previous studies, associated with an increased risk of childlessness, suggesting that treatment improvements may have positively impacted the reproductive health of these patients.’

In other findings, the risks for pre-eclampsia, newborns being small for gestational age, preterm delivery, non-elective Caesarean sections, and need of neonatal intensive care were increased in many IMDs.

‘Particularly, SLE, [Sjögren‘s syndrome] SS, type 1 diabetes, and Addison’s disease showed >2-fold risks for some of these outcomes,’ the researchers reported.

‘Of the rheumatic diseases, SLE and SS conferred the largest risk increases on perinatal adverse event outcomes.’

In most rheumatic diseases, moderate (1.1–1.5-fold) risk increases were observed for diverse adverse pregnancy outcomes, with similar effects in IBD, coeliac disease, asthma, ITP and psoriasis.

Lead author Dr Anne Kerola, resident in rheumatology at the Helsinki University Hospital in Finland, said despite seeing an elevated risk for diverse childbearing problems in rheumatic and other IMDs, many of the complications were still fairly rare.

‘Family planning should actively be discussed between patients, both men and women, with rheumatic diseases and their healthcare providers,’ she said.

‘Pregnancies in women with rheumatic diseases are carefully followed up to tailor medications appropriately, which helps reduce risks.’

IMDs have also been linked to other adverse outcomes including an increased risk of atrial fibrillation (AF). In a prospective study published last year, Dutch researchers found there were elevated risks of AF for those with several autoimmune diseases including Crohn’s disease (HR = 1.23), ulcerative colitis (HR = 1.17), rheumatoid arthritis (HR = 1.39), SLE (HR = 1.82) and systemic sclerosis (HR = 2.32).

Anti-IL17 peptide shows high clinical efficacy for immune-related inflammatory diseases

23rd August 2023

An anti-IL17 peptide sequence has demonstrated high clinical efficacy in models of immune-mediated inflammatory conditions, warranting further clinical evaluation.

Researchers from the University of Birmingham, together with colleagues from the University of Naples Federico II, developed a novel anti-IL17 peptide sequence with greater activity and potentially fewer side effects than existing biologic therapies for immune-mediated inflammatory conditions.

Biologic therapies targeting interleukins, such as anti-IL-17, anti-IL12/23 and anti-IL23, have become established therapies in the treatment of immune-mediated inflammatory conditions such as psoriasis, rheumatoid arthritis and inflammatory bowel disease. However, these novel agents often show low therapeutic efficacy and immunogenicity in certain patient subgroups, thereby limiting their effectiveness.

Writing in the Annals of Rheumatic Disease, the researchers set out to improve the coverage and efficacy of antibodies targeting IL-17A and/or IL-17F.

Anti-IL17 peptide

Using murine and human IL-17A/F protein sequences, the researchers identified a bioactive 20-amino acid IL-17A/F-derived peptide that mimicked the pro-inflammatory actions of the full-length proteins.

Once this sequence had been determined, the team generated a novel anti-IL-17 neutralising monoclonal antibody directed against the sequence, which they named Ab-IPL-IL17™.

Using tissue and animal studies, the researchers were able to demonstrate that Ab-IPL-IL-17 was capable of effectively reversing the pro-inflammatory, pro-migratory actions of not only the 20-amino acid peptide sequence but also IL-17A/F.

In addition, when compared with secukinumab – the current gold-standard biologic – the anti-IL17 peptide gave rise to less off-target immune-related effects. There was also no reduction in platelet counts or an increase in the level of lymphocytes.

In a proof-of-concept study for rheumatoid arthritis, the anti-IL17 antibody inhibited the pro-inflammatory actions of chronically inflamed fibroblasts within the rheumatoid joint.

Similarly, using serum samples from treatment naive inflammatory bowel disease patients, their novel antibody was able to deplete plasma IL-17A, suggesting a potential to alleviate pathological pro-inflammatory changes.

The authors described how Ab-IPL-IL-17, which did not generate immunogenicity, lymphocytosis or thrombocytopenia properties, highlighted potential clinical superiority over current therapies.

They called for future clinical trials to address the varying requirements of Ab-IPL-IL17 as an alternative biological therapy for treating patients with immune-mediated inflammatory diseases.