Rohan Machhar and Dafna D. Gladman, MD, on MiR-21-5p for Predicting Disease Activity in Patients With PsA

MicroRNA-21-5p (miR-21-5p) expression is upregulated in patients with psoriatic arthritis (PsA), which suggests that the molecule may be a potential biomarker of inflammation in psoriatic disease, according to findings from a study presented at the 2019 ACR/ARP Annual Meeting.¹

Moreover, the molecule may also be able to predict which patients will benefit from subcutaneous methotrexate vs oral methotrexate.

Rheumatology Consultant spoke with the lead authors to find out more about their research.

Rohan Machhar is a research associate at the Krembil Research Institute in Toronto, Canada, and Dafna D. Gladman, MD, is professor of medicine at the University of Toronto, senior scientist at the Krembil Research Institute, deputy director of the Centre for Prognosis Studies in The Rheumatic Diseases at Toronto Western Hospital, in Toronto, Canada.

RHEUM CON: What is the need for more biomarkers for PsA?

Rohan Machhar: We know that the disease has a very complex pathogenesis, and 30% of patients with psoriasis develop PsA. It is very important to identify those patients early, since delay in diagnosis leads to poor outcomes.

If we had a biomarker that could predict which patients will develop PsA, it would be amazing. We have C-reactive protein (CRP), but then we need something else as well, a laboratory‑based marker, which would work excellently for these patients.

Dafna Gladman: This particular microRNA, 21‑5p, seems to be a very good biomarker, both for the development of PsA and response to therapy. We have done studies, and our colleagues in Dublin have done studies, that demonstrate that early diagnosis and early intervention actually are good for the patients. Saying it another way, even a 6‑month delay in diagnosis is detrimental in terms of outcome. We are looking for a biomarker to identify these patients early.

Now, we currently have some clinical biomarkers. We know that patients with psoriasis who have severe skin disease, nail lesions, or scalp lesions, have some other genetic factors, but those factors are not conclusive—not even close to 100%.

For example, if a patient presents first to a family doctor, a family doctor is not going to assess for genetic risk factors. If we had a blood test that could predict who is most likely to develop PsA, it would allow patients to either be referred to a rheumatologist right away or be asked about the presence of joint pain and skin lesions. This is important for family physicians and dermatologists.

RHEUM CON: Why did you conduct the study?

RM: I had worked on microRNAs before. I saw a publication in which the researchers assessed microRNAs in patients in PsA and rheumatoid arthritis. I thought it would be interesting to evaluate microRNAs in patients with psoriasis and then PsA, because that is our cohort population at the Krembil Research Institute in Toronto.

We decided that we would conduct this study, but we would look into this particular microRNA, which had been previously found in a microRNA study in another group and try to validate it in our cohort and see what we find. Not only looking at the difference, but also looking at the mechanism in which it might affect these patients.

RHEUM CON: What is the most important finding from your study?

RM: MiRNA-21-5p is a potential marker for inflammation, because it had been correlating with the swollen joint counts. Also, when we looked at the treatment response, it showed that this microRNA could be a marker of treatment response, as well, to methotrexate in particular.

We further looked to see whether there was a response based on subcutaneous methotrexate. We saw that the patients who had received subcutaneous methotrexate had a further decline in this microRNA, as well as a decline in disease activity.

We can probably say that it may help predict who might respond to treatment, but moreover, we can also say that subcutaneous methotrexate works better among these patients, compared with oral methotrexate.

RHEUM CON: What is the key take-home message for practicing rheumatologists?

RM: I would definitely say that looking for biomarkers is the key, and research in biomarkers should continue, regardless, until we find a biomarker that is highly predictive and that could be validated and replicated in different cohorts.

It is like producing vaccinations. I can produce a vaccine that could be good for my region, but if I am testing it in a different region, and it does not work there, it is not a good vaccine. That is what I would want to convey. The cohort size was a limitation in this study, so our findings need to be validated in a bigger cohort or a different cohort.

DG: Rohan’s discovery of the miR‑21‑5p as a biomarker, both for the development of PsA and for response to methotrexate, is a very important finding. Now, is it the only MicroRNA? Probably not. Does it work for everybody? Probably not. An algorithm or a group of biomarkers are probably going to have to be put together as a test. But this study is the beginning, so I think it is very important.

Reference:

1. Machhar R, Ye J(Y), Pollock R, Gladman D. miR-21-5p expression as a marker of treatment response in psoriatic arthritis patients [abstract 1909]. Paper presented at: 2019 ACR/ARP Annual Meeting; November 8-13, 2019; Atlanta, GA. https://acrabstracts.org/abstract/mir-21-5p-expression-as-a-marker-of-treatment-response-in-psoriatic-arthritis-patients/. Accessed November 6, 2019.