Clinical trial NCT04244916: MPA AUC Monitoring in Patients Receiving MMF for Diffuse Cutaneous or Pulmonary Involvement in Systemic Sclerosis
Official title: Prospective Study to Investigate the Relevance of Monitoring Area Under the Curve of Mycophenolic Acid in Patients Receiving Mycophenolate Mofetil to Treat a Diffuse Cutaneous or a Pulmonary Involvement of Systemic Sclerosis
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Systemic Sclerosis
Keywords: Systemic sclerosis
diffuse
interstitial lung disease
therapeutic drug monitoring (TDM)
mycophenolate mofetil
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2020-01-28
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients receiving MMF for another indication than skin or lung damage to systemic sclerosis (after lung transplantation for example).

* Contraindication to MMF: Hypersensitivity to the product. Pregnancy.
* In patients treated for skin damage:

  * Failure to take other concomitant immunosuppressive treatments or in the last 3 months except corticosteroid therapy.
  * No treatment with biotherapy in the last 6 months
* In patients treated for lung damage:

  * No treatment with biotherapy in the last 6 months

Brief summary: To define a target value of AUC MPA to improve the modified Rodnan score and / or respiratory impairment (DLCO or FVC) at one year in patients receiving MMF for the treatment of diffuse cutaneous or interstitial lung damage of systemic sclerosis.

Detailed description: In the treatment of autoimmune diseases, MMF is almost always prescribed at a fixed dose, regardless of AUC, or based on the target of AUC determined for organ transplantation. One study looked at determining an "effective" AUC threshold in systemic lupus erythematosus, which appears to be 35mg / h / l. This was also done for ANCA vasculitis.

We therefore conducted this study to determine a correlation between AUC MPA and the effectiveness of MMF in systemic sclerosis.

Prospective, observational, open study.

Main objective: define a target value of AUC MPA to improve the modified Rodnan score and / or respiratory impairment (DLCO or FVC) at one year in patients receiving MMF for the treatment of diffuse skin involvement or pulmonary function in systemic sclerosis.

The main endpoint will be evaluated on the evolution of the modified Rodnan score at 1 year after the initiation of MMF and / or the evolution of FVC and DLCO at 1 year after the initiation of MMF.

Eligibility criteria: Inclusion Criteria:

* Systemic sclerosis meeting the ACR / EULAR criteria of 2013
* Equal or more than 18 years old, able to freely consent to study
* In patients treated for skin damage:

  * Diffuse skin sclerosis (rising above the elbows and / or knees)
  * First clinical sign of systemic sclerosis outside of Raynaud's phenomenon going back less than three years
  * Failure to take other concomitant immunosuppressive treatments or in the last 3 months except corticosteroids.
* In patients treated for lung damage:

  * Interstitial lung damage identified on chest CT, chest x-ray
  * Any duration of progression of systemic scleroderma
  * Prescription of MMF in first line or in relay of a treatment with Cyclophosphamide.
  * Absence of biotherapy in the last 6 months.

Exclusion Criteria:

-

Primary outcomes:
measure: Skin efficacy
timeFrame: 1 year
Secondary outcomes:
measure: Pulmonary efficacy.1
timeFrame: 1 year
measure: Pulmonary efficacy.2
timeFrame: 6 months and 1 year
Other outcomes:
Locations:
city: Paris
country: France
facility: Cochin hospital, AP-HP
Study officials:
References:
citation: van Gelder T, Le Meur Y, Shaw LM, Oellerich M, DeNofrio D, Holt C, Holt DW, Kaplan B, Kuypers D, Meiser B, Toenshoff B, Mamelok RD. Therapeutic drug monitoring of mycophenolate mofetil in transplantation. Ther Drug Monit. 2006 Apr;28(2):145-54. doi: 10.1097/01.ftd.0000199358.80013.bd.
citation: Zahr N, Arnaud L, Marquet P, Haroche J, Costedoat-Chalumeau N, Hulot JS, Funck-Brentano C, Piette JC, Amoura Z. Mycophenolic acid area under the curve correlates with disease activity in lupus patients treated with mycophenolate mofetil. Arthritis Rheum. 2010 Jul;62(7):2047-54. doi: 10.1002/art.27495.
citation: Chaigne B, Gatault P, Darrouzain F, Barbet C, Degenne D, Francois M, Szymanski P, Rabot N, Golea G, Diot E, Maillot F, Lebranchu Y, Nivet H, Paintaud G, Halimi JM, Guillevin L, Buchler M. Mycophenolate mofetil in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis: a prospective pharmacokinetics and clinical study. Clin Exp Immunol. 2014 May;176(2):172-9. doi: 10.1111/cei.12246.