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Efficacy of Rituximab in Refractory Inflammatory Myopathies Associated with Anti- Synthetase Auto-Antibodies: An Open-Label, Phase II Trial.

Allenbach Y, Guiguet M, Rigolet A, Marie I, Hachulla E, Drouot L, Jouen F, Jacquot S, Mariampillai K, Musset L, Grenier P, Devilliers H, Hij A, Boyer O, Herson S, Benveniste O - PLoS ONE (2015)

Bottom Line: Secondary endpoints were normalization of creatine kinase (CK) level, ILD improvement based on forced vital capacity and/or diffuse capacity for carbon monoxide, and number and/or doses of associated immunosuppressants.CK level decreased from 399 IU/L (range, 48-11,718) to 74.5 IU/L (range, 40-47,857).Corticosteroid doses decreased from 52.5 mg/d (range, 10-70) to 9 mg/d (range, 7-65) and six patients had a decrease in the burden of their associated immunosuppressants.

View Article: PubMed Central - PubMed

Affiliation: Département de Médecine Interne et Immunologie Clinique, Centre de Référence des Pathologies Neuromusculaires Paris Est, UPMC, APHP, INSERM, UMR 974, DHU i2B, Hôpital Pitié-Salpêtrière, Paris, France.

ABSTRACT

Objective: Anti-synthetase syndrome (anti-SS) is frequently associated with myositis and interstitial lung disease (ILD). We evaluated prospectively, in a multicenter, open-label, phase II study, the efficacy of rituximab on muscle and lung outcomes.

Methods: Patients were enrolled if they were refractory to conventional treatments (prednisone and at least 2 immunosuppressants). They received 1 g of rituximab at D0, D15, and M6. The primary endpoint was muscular improvement based on manual muscular testing (MMT10, Kendall score in 10 muscles) at M12. Secondary endpoints were normalization of creatine kinase (CK) level, ILD improvement based on forced vital capacity and/or diffuse capacity for carbon monoxide, and number and/or doses of associated immunosuppressants.

Results: Twelve patients were enrolled, and 10 completed the study. Only 2 patients presented an improvement of at least 4 points on at least two muscle groups (primary end-point). Overall, seven patients had an increase of at least 4 points on MMT10. CK level decreased from 399 IU/L (range, 48-11,718) to 74.5 IU/L (range, 40-47,857). Corticosteroid doses decreased from 52.5 mg/d (range, 10-70) to 9 mg/d (range, 7-65) and six patients had a decrease in the burden of their associated immunosuppressants. At baseline, all 10 patients presented with ILD. At M12, improvement of ILD was observed in 5 out of the 10 patients, stabilization in 4, and worsening in 1.

Conclusions: This pilot study of rituximab treatment in patients with refractory anti-SS provided data on evolution of muscular and pulmonary parameters. Rituximab should now be evaluated in a larger, controlled study for this homogenous group of patients.

Trial registration: Clinicaltrials.gov NCT00774462.

No MeSH data available.


Related in: MedlinePlus

Evolution of strength and CK levels from baseline to months 18.(A) MMT10 using Kendall score. (B) CK level. The continuous line and the dotted line represent the median Kendall score and the median CK level, respectively.
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pone.0133702.g002: Evolution of strength and CK levels from baseline to months 18.(A) MMT10 using Kendall score. (B) CK level. The continuous line and the dotted line represent the median Kendall score and the median CK level, respectively.

Mentions: At M12, only 2 patients achieved the primary end point, which required improvement in 2 different muscle groups. The median MMT10 score increased from 92.5 (range, 75–97) at baseline to 95.5 (range, 77–100) at M12 with a median variation of +5 points (range, -15 to +13; p = 0.43). Overall 7 of 10 patients had an increase of at least 4 points (70%, 95%CI, 35–93%). One patient was stabilized and 2 worsened (Table 1 and Fig 2).


Efficacy of Rituximab in Refractory Inflammatory Myopathies Associated with Anti- Synthetase Auto-Antibodies: An Open-Label, Phase II Trial.

Allenbach Y, Guiguet M, Rigolet A, Marie I, Hachulla E, Drouot L, Jouen F, Jacquot S, Mariampillai K, Musset L, Grenier P, Devilliers H, Hij A, Boyer O, Herson S, Benveniste O - PLoS ONE (2015)

Evolution of strength and CK levels from baseline to months 18.(A) MMT10 using Kendall score. (B) CK level. The continuous line and the dotted line represent the median Kendall score and the median CK level, respectively.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4634756&req=5

pone.0133702.g002: Evolution of strength and CK levels from baseline to months 18.(A) MMT10 using Kendall score. (B) CK level. The continuous line and the dotted line represent the median Kendall score and the median CK level, respectively.
Mentions: At M12, only 2 patients achieved the primary end point, which required improvement in 2 different muscle groups. The median MMT10 score increased from 92.5 (range, 75–97) at baseline to 95.5 (range, 77–100) at M12 with a median variation of +5 points (range, -15 to +13; p = 0.43). Overall 7 of 10 patients had an increase of at least 4 points (70%, 95%CI, 35–93%). One patient was stabilized and 2 worsened (Table 1 and Fig 2).

Bottom Line: Secondary endpoints were normalization of creatine kinase (CK) level, ILD improvement based on forced vital capacity and/or diffuse capacity for carbon monoxide, and number and/or doses of associated immunosuppressants.CK level decreased from 399 IU/L (range, 48-11,718) to 74.5 IU/L (range, 40-47,857).Corticosteroid doses decreased from 52.5 mg/d (range, 10-70) to 9 mg/d (range, 7-65) and six patients had a decrease in the burden of their associated immunosuppressants.

View Article: PubMed Central - PubMed

Affiliation: Département de Médecine Interne et Immunologie Clinique, Centre de Référence des Pathologies Neuromusculaires Paris Est, UPMC, APHP, INSERM, UMR 974, DHU i2B, Hôpital Pitié-Salpêtrière, Paris, France.

ABSTRACT

Objective: Anti-synthetase syndrome (anti-SS) is frequently associated with myositis and interstitial lung disease (ILD). We evaluated prospectively, in a multicenter, open-label, phase II study, the efficacy of rituximab on muscle and lung outcomes.

Methods: Patients were enrolled if they were refractory to conventional treatments (prednisone and at least 2 immunosuppressants). They received 1 g of rituximab at D0, D15, and M6. The primary endpoint was muscular improvement based on manual muscular testing (MMT10, Kendall score in 10 muscles) at M12. Secondary endpoints were normalization of creatine kinase (CK) level, ILD improvement based on forced vital capacity and/or diffuse capacity for carbon monoxide, and number and/or doses of associated immunosuppressants.

Results: Twelve patients were enrolled, and 10 completed the study. Only 2 patients presented an improvement of at least 4 points on at least two muscle groups (primary end-point). Overall, seven patients had an increase of at least 4 points on MMT10. CK level decreased from 399 IU/L (range, 48-11,718) to 74.5 IU/L (range, 40-47,857). Corticosteroid doses decreased from 52.5 mg/d (range, 10-70) to 9 mg/d (range, 7-65) and six patients had a decrease in the burden of their associated immunosuppressants. At baseline, all 10 patients presented with ILD. At M12, improvement of ILD was observed in 5 out of the 10 patients, stabilization in 4, and worsening in 1.

Conclusions: This pilot study of rituximab treatment in patients with refractory anti-SS provided data on evolution of muscular and pulmonary parameters. Rituximab should now be evaluated in a larger, controlled study for this homogenous group of patients.

Trial registration: Clinicaltrials.gov NCT00774462.

No MeSH data available.


Related in: MedlinePlus