BIOHOPE is developing a blood-based in vitro diagnosis test to personalize immunosuppressant therapy for Rheumatoid Arthritis under treatment with immunosuppressant drugs. This diagnostic kit been named Immunobiogram® (IMBG) – Arthritis.

 

Inmunobiogram® is being studied in Rheumatoid Arthritis under a comprehensive clinical plan program, which includes a first proof of concept clinical study in 100 patients (BH-Pilot) and a subsequent validation study

“BH-Arthritis” is a clinical study which aims to evaluate the feasibility and potential clinical utility of a specifically-developed Inmunobiogram® for Rheumatoid Arthritis. This first-in-clinic study is to be done in collaboration with the Rheumatology Unit of “Reina Sofía” Hospital (Córdoba) and “Maimonides Institute of Biomedical Research”.

Worldwide, the annual incidence of RA is approximately three cases per 10,000 population, and the prevalence rate is approximately 1%, increasing with age and peaking between the ages of 35 and 50.

Clinical course of RA is very variable. More frequently, it follows a pattern of exacerbations and remissions. Outcomes are variable; some patients experience a relatively self-limited disease, whereas others have a chronic progressive illness. While there is no cure for RA, therapy for RA has improved greatly in the past 30 years. Today, patients begin their treatment with disease-modifying anti-rheumatic drugs, or DMARDs, which slow the progression of the disease. DMARDs have greatly improved the symptoms, function and quality of life for patients with RA.

The following chart, named ‘TREAT-TO-TARGET’, more precisely summarizes the preferred strategy for treatment of RA. The primary goals in the treatment of RA are to control inflammation and slow or stop disease progression. Currently, setting the goal, as well as initiating and adapting the therapy, should be done as a shared decision with the patient.

inmunograma artritis. Treat-to target

Nevertheless, outcomes in RA are compromised when diagnosis and treatment are delayed. Despite treatments, approximately 40% of patients with this disease become disabled after ten years.

Unfortunately, DMARDs and also biological therapy are selected by trial and error. A personalized immunosuppressant approach cannot currently be implemented in clinical practice due to the lack of evidence-based tools towards selection of the optimal immunosuppressive therapy.

We are working to develop BIOHOPE’s IBMG-AR as an In Vitro Diagnostic Tool that will measure the sensitivity of patients to Immunosuppressant medication (IMS), and on top of that, detect patients with bad prognosis due to IMS low sensitivity. This information will allow to optimize treatment as soon as possible and guarantee a better outcome for the patient.

Only a conventional 10mL blood sample from the patient is needed to run the immunoassay. It is based on PBMCs 3D culture in semi-solid matrix submitted to specific stimulation which replicates antigen presentation. Inmunobiogram® mimics immune response in which PBMC replicate and expand (C+), and this response is compared with no stimulation (C-) and with stimulation in presence of immunosuppressants (C+ with IMs). Data will be analyzed with a software and output is an evaluation of the sensitivity degree of patient´s circulating immune cells to a panel of immunosuppressant most recommended in clinical guidelines and most used in the clinical setting. The bioassay uses well known immunosuppressants but it can be adapted for testing new compounds against marketed ones. IMBG allows for a direct comparison between several immunosuppressant drugs in terms of immunosuppressive potency for each specific patient at the time the immunoassay is run. As the immunological system is very dynamic and can be affected by many factors, it is anticipated that Inmunobiogram® would be better used as a test to monitor patient´s intrinsic response to immunosuppressant drugs over time.

Drugs aimed to be tested in Inmunobiogram® – Arthritis are:

 Clasicc DMARDs

 

Corticoids

 

New medicines

Methotrexate

Hydroxychloroquine


Metilprednisolone


 

Tofacinib

Leflunomide

Tacrolimus


 

 

 

Sulfasalazine

Ciclosporin


 

 

 

Inmunobiogram®- AR is an In Vitro Diagnostic laboratory test that is expected to combine a biotechnological KIT and a software for data interpretation. Inmunobiogram® bioassay is to be read with a luminometer or similar device. An automatic mathematical algorithm will be developed that, using rough data directly coming from the luminometer, would offer a SCORE that evaluates patient´s individual sensitivity to the immunosuppressant panel of drugs. Due to its design and easy-to-read output, we anticipate it will be easily used in the clinical setting.

A European patent was presented in 2017 to protect this invention and further IP protection is foreseen for IMBG-AR.

BH-Arthritis Study

BH-Arthritis study is a clinical study to be conducted between 2018 and 1-2Q 2019 to evaluate the feasibility and potential clinical utility of a specifically-developed Inmunobiogram® for Rheumatoid Arthritis.

It will include 100 Rheumatoid Arthritis patients classified in the following categories:

  1. Naïve patients (DAS>2)
  2. Chronic patients under treatment with DMARDs with low disease activity
  3. Chronic patients under treatment with DMARDs with high disease activity

We expect BH- Arthritis to be a clinical study that would demonstrate:

  1. Inmunobiogram-AR (IMBG-AR) will be feasible in patients with Rheumatoid Arthritis at various disease stages and clinical scenarios.
  2. Inmunobiogram-AR (IMBG-AR) will offer as an output an in vitro potency evaluation of Immunosuppressant drugs (IMs) that will be correlated with sensitivity grades of the patient to a panel of IMs.
  3. A significant proportion of patients with non-controlled RA will show low-sensitivity patterns in IMBG-AR to the medication they are taking.

This first-in-clinic study is to be done in collaboration with the Rheumatology Unit of “Reina Sofía” Hospital (Córdoba) and “Maimonides Institute of Biomedical Research”, and it is expected to start in 2Q2018.