Limits...
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: 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.This pilot study of rituximab treatment in patients with refractory anti-SS provided data on evolution of muscular and pulmonary parameters.

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

Anti-Jo-1 titer variation and B-lymphocyte depletion.Anti-Jo-1 titer was monitored for the 9 patients who terminated the study (the tenth had anti-PL-7). On the right side, 4 boxes represent the status at M12 (vs M0) concerning manual muscular testing (MM10), creatine kinase level (CK), treatment modification (treatment), and forced vital capacity (FVC). Black represents worsening, grey area represent no change, and white represents an improvement. Concerning CK, black shows an increased level at M12 and white a normal level.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4634756&req=5

pone.0133702.g006: Anti-Jo-1 titer variation and B-lymphocyte depletion.Anti-Jo-1 titer was monitored for the 9 patients who terminated the study (the tenth had anti-PL-7). On the right side, 4 boxes represent the status at M12 (vs M0) concerning manual muscular testing (MM10), creatine kinase level (CK), treatment modification (treatment), and forced vital capacity (FVC). Black represents worsening, grey area represent no change, and white represents an improvement. Concerning CK, black shows an increased level at M12 and white a normal level.

Mentions: For the nine anti-Jo-1 aAbs–positive patients, it was possible to follow the titer of aAbs (Fig 6). No significant variations among the anti-Jo-1 titers were observed over time (median, 163 AU/mL; range, 94–357) at M0 vs. 211 AU/mL (range, 95–309) at M12 (median variation +1 AU/mL; range, -50 to +124; p = 0.58) (Fig 6). Nevertheless, the 2 patients (patient 5 and 6) who presented at M12 with an important increase of their titer (increases of 42% and 121%, respectively; Fig 6) were those with both MMT10 scores and CK levels lower than at baseline.


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)

Anti-Jo-1 titer variation and B-lymphocyte depletion.Anti-Jo-1 titer was monitored for the 9 patients who terminated the study (the tenth had anti-PL-7). On the right side, 4 boxes represent the status at M12 (vs M0) concerning manual muscular testing (MM10), creatine kinase level (CK), treatment modification (treatment), and forced vital capacity (FVC). Black represents worsening, grey area represent no change, and white represents an improvement. Concerning CK, black shows an increased level at M12 and white a normal level.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0133702.g006: Anti-Jo-1 titer variation and B-lymphocyte depletion.Anti-Jo-1 titer was monitored for the 9 patients who terminated the study (the tenth had anti-PL-7). On the right side, 4 boxes represent the status at M12 (vs M0) concerning manual muscular testing (MM10), creatine kinase level (CK), treatment modification (treatment), and forced vital capacity (FVC). Black represents worsening, grey area represent no change, and white represents an improvement. Concerning CK, black shows an increased level at M12 and white a normal level.
Mentions: For the nine anti-Jo-1 aAbs–positive patients, it was possible to follow the titer of aAbs (Fig 6). No significant variations among the anti-Jo-1 titers were observed over time (median, 163 AU/mL; range, 94–357) at M0 vs. 211 AU/mL (range, 95–309) at M12 (median variation +1 AU/mL; range, -50 to +124; p = 0.58) (Fig 6). Nevertheless, the 2 patients (patient 5 and 6) who presented at M12 with an important increase of their titer (increases of 42% and 121%, respectively; Fig 6) were those with both MMT10 scores and CK levels lower than at baseline.

Bottom Line: 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.This pilot study of rituximab treatment in patients with refractory anti-SS provided data on evolution of muscular and pulmonary parameters.

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