The SOLVO MDQ Kit™

 

SOLVO MDQ Kit™ is the first commercially available CE-IVD approved clinical diagnostic kit for the detection of MDR protein function (MDR1, MRP1, and BCRP) by quantitative flow cytometry.

Learn more about how your patients can benefit from MDR protein function determination.

 

Autoimmune Diseases

Learn more about the application of SOLVO MDQ KitTM in Rheumatoid Arthritis

Hematologic Malignancies

Learn more about the application of SOLVO MDQ KitTM in Hematologic Malignancies

MDQuest Ltd.

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For clinical immunologists

 

In rheumatoid arthritis (RA) measurement of MDR protein function in activated T lymphocytes correlates with disease activity, disease prognosis, and drug intolerance. Testing of MDR pump function with the SOLVO MDQ KitTM has therefore multiple benefits for RA patients: reducing the risk of drug intolerance for MTX, dynamic disease activity monitoring to achieve earlier remission and drug efficiency monitoring. SOLVO MDQ KitTM is a biomarker-based diagnostic tool for better RA management. 

 

Page content:

I. Need for biomarkers in rheumatoid arthritis disease management

II. MDR proteins as biomarkers in rheumatoid arthritis

III. Applications of the SOLVO MDQ KitTM in rheumatoid arthritis

IV. Availability

 

I. Need for biomarkers in rheumatoid arthritis disease management

Disease management of RA is a costly and challenging task for a notable part of patients. As standard treatment Methotrexate or other synthetic DMARDs, methyl-prednisolon and numerous new biologicals are used in monotherapy or in combination to combat the disease progression. Despite the new generations of biologicals, there still remains a large unmet patient need in the tailored treatment of RA.

  1. RA is a disease with a highly variable prognosis, quickly leading to irreversible disability

As stated in the EULAR (European League Against Rheumatism) and NICE (National Institute for Health and Clinical Excellence ) therapeutic guidelines1 the primary target should be disease remission; however, low disease activity may be an acceptable alternative therapeutic goal. Until the desired treatment target is reached (usually 1–6 months), drug therapy should be adjusted at least every 3 months.

  1. All current therapies have poor response rates and serious side effects, particularly if the first treatment is delayed, and there is no predictive biomarker available for drug efficiency to choose between therapies upfront

  • MTX remains the first choice in early RA treatment showing remission-like response rates up to 50%2, however, at least 10-30% of patients suffer from various side effects3.

  • The prevalence of MTX intolerance was found to be 11% 4
  • Other synthetic DMARDS: half of all treatments had been discontinued after 16 months5 due to lack of efficacy (25% of all prescriptions and 37% of all discontinuations) followed by toxicity (20% of all prescriptions and 46% of all discontinuations).

  • Biological DMARDs: Up to 50% of patients do not respond6.

  1. There is no good disease activity marker available on the market to monitor the course of disease

Regular monitoring of disease activity is particularly important, especially in patients with high disease activity and there is a need for monthly assessment of the disease status7. This effort is currently best supported by composite scoring disease activity evaluation tools (eg: DAS28, ACR, SDAI, CDAI). Despite the emerging pool of disease activity biomarkers8 , only a few made it to clinical acceptance so far: autoantibodies like RF, anti-CCP, and inflammatory markers (e.g. CRP, IL6).

 

II. MDR proteins as biomarkers in rheumatoid arthritis

Historically, the multidrug resistance (MDR) phenomenon has been proven in hematological malignancies, where the prevalence of efflux transporter (e.g. P-glycoprotein, MRP1, BCRP) mediated drug resistance is about 40%9. In the last decade, several studies examined the possible role of MDR proteins in autoimmune disorders, e.g. RA, and focused on the correlation with disease activity, therapy responsiveness, and progression (outcome).

 

1. In vitro data:

A number of immunosuppressive drugs used in RA therapy as MTX and other synthetic DMARDs appear to be substrates of these efflux transporters confirmed by in vitro assays10. This means that MTX and other synthetic DMARDS are eliminated by drug efflux pumps from the target cells, which can be manifested in various side effects, inefficacy or intolerance of the given drug. In the case of some immunosuppressive drugs, the therapeutic window is narrow, making it difficult to manage the disease by simply increasing the daily dose.

Transporters and drug interactions based on in vitro assays

Common name (ABC code)

Pharmacologic substrate

P-gp, MDR1 (ABCB1)

MTX, Chloroquine, CSA, Prednisone, dexamethasone

BCRP (ABCG2)

MTX, SSZ, Leflunomide

MRP1 (ABCC1)

MTX, Chloroquine

 

2. Clinical data:

Research data suggests that the MDR drug transporters might play a role in immune regulation11. representing the most important efflux mechanism for several inflammatory signaling molecules, such as the eicosanoids (prostanoids and leukotrienes), which are among the mediators of chronic inflammation12.


In addition, several studies have showed the clinical significance of MDR as prognostic and/or predictive marker in immunosuppressive therapies for active RA using MTX, other synthetic DMARDs, or biological DMARDs. The methods included the measurement of functional activity, gene- or protein expression of MDR transporters, mainly P-glycoprotein. Llorente et al found higher P-gp activity in refractory RA than the non-refractory group13. Agarwal et al established that the percentage of cells expressing P-glycoprotein were significantly higher in the MTX-naive and MTX-refractory groups than the healthy controls at baseline, and they also found that the expression of P-glycoprotein in RA correlated with disease activity status14. Tsujimara et al reported that Etanercept therapy in refractory RA resulted in an almost complete disappearance of the P-gp- and CD69-high-expressing subgroups15. Moreover, Heijden et al revealed that BCRP may play a role in the efficacy of specific other synthetic DMARDs in RA treatment besides P-glycoprotein. Since MTX is an in vitro substrate for both P-gp, BCRP and MRP1, and Leflunomide is a high-affinity substrate for BCRP, these transporters may contribute to the reduced therapeutic efficacy of these therapies16. Wolf et al found that the determination of MDR may predict responsiveness to MTX17.

Furthermore, other synthetic DMARDs may also induce the expression of MDR proteins leading to secondary resistance18.

 

III. Applications of the SOLVO MDQ KitTM in rheumatoid arthritis See the application options harmonised with the EULAR guideline

1. Disease onset (Option#1 & option# 2 Phase I., EULAR guideline)

1.1. In the case of new RA patients, measurement of initial MDQ value that – in view of polyarthritis, ACPA and Rheumatoid factor and alongside ESR, DAS28 values - could be predictive of the activity and severity of the clinical course of the disease.

1.2 New, methylprednisolone (MP) therapy receiving patients– MDQ measurement every month for 3 to 6 months to assist the doctor in deciding when to quit the MP.

1.3 MDQ measurement in the case of new MTX+NSAID or MTX+small dosage MP receiving patients if there is a relapse (flare).

2. Developed RA (If initial treatment was unsuccessful) (option#3 option#4 & option#5 Phase II., EULAR guideline)

2.1 Combined DMARD (eg. MTX+LF) treatment– MDQ measurement every 3 months, or as frequently as needed in the case of a relapse.

2.2 Prior to TNF inhibitor/first-line biologics therapy (Tocilizumab) and following the treatment – MDQ measurements every month for 3 months, then every 3 months.

3. Late stage RA (option#6a, option#6b & option#7 Phase III., EULAR guideline)

3.1 MDQ measurement every 3 months (monitoring MDR activity) if treatment is successful, or as frequently as needed in the case of a relapse.

 

MDRinRA

 

MDRinRA 2

 

IV. Availability

PRODUCT SIZE CAT. NO.
SOLVO MDQ Kit™ 10 assays MDQ0101D

 

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Disclaimer: Our value proposition is based on expert opinion and the best available evidence and is harmonized with the EULAR guideline. However this publication is an informative document intended for informational purposes only and does not constitute medical practice nor medical advice.


1. Smolen et al. Ann Rheum Dis 2010
2. Yazici et al. Exp Rev Clin Pharmacol 2010
3. Chemocare.com is sponsored by the Scott Hamilton Cancer Alliance for Research, Education and Survivorship Initiative at the Cleveland Clinic Taussig Cancer Center.
4. Ćalasan Arthritis Res Ther. 2013 Arthritis Res Ther. 2013
5. Capell J Rheumatology 2002
6. Isaacs JD Nature Reviews Immunology 2010
7. Smolen et al. Ann Rheum Dis 2010
8. Taylor et al. Autoimmune Diseases 2011, Carrasco et al. Rheumatology Reports 2010
9. Leonard GD et al The Oncologist 2003
10. Norris Int J Cancer 1996 , Chen Cancer Res 2003, Zeng Cancer Res 2001, Kis Ann Rheum Dis 2009 , Dahan Am J Physiol Gastrointest Liver Physiol 2009 , Jansen 2003
11. Yvonne Richaud-Patin 2003
12. Fletcher Net Rev Canc 2010 , Oerlemans 2006
13. Llorente 2000
14. Agarwal Clin Rheumatol 2009
15. Tsujimura 2010
16. Heijden 2009
17. Wolf et al. Ann Rheum Dis 2005
18. Oerlemans 2006