Rituximab Helps in Sjgren's Syndrome
By Nancy Walsh, Contributing Writer, MedPage Today
Published: April 06, 2010
Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston and
Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner Earn CME/CE credit
[if: In a small study, the monoclonal antibody rituximab improved the salivary function and other symptoms such as arthritis in patients with Sjgren's syndrome.]
The chimeric monoclonal antibody rituximab (Rituxan) improved both salivary function and the extraglandular manifestations of primary Sjgren's syndrome, a small prospective study found.
Compared with baseline, the stimulated whole saliva flow rate improved significantly among patients given two infusions of rituximab (P=0.018 at week five and P=0.004 at week 12), according to Jiska M. Meijer, MD, and colleagues from the University of Groningen in the Netherlands.
In contrast, patients receiving placebo experienced declines in salivary gland function consistent with the natural history of Sjgren's syndrome, the researchers reported in the April issue of Arthritis & Rheumatism.
The inflammation of the salivary and lacrimal glands seen in this systemic autoimmune disease often is accompanied by extraglandular manifestations including Raynaud's phenomenon, arthritis, and severe fatigue.
B-cell hyperactivity, reflected by elevated levels of rheumatoid factor and other autoantibodies, is a typical finding in Sjgren's syndrome.
No targeted therapies have thus far been made available, but pilot trials of rituximab, which binds to the CD20 surface antigen on B cells, have shown promising improvements in symptoms for six to nine months.
So Meijer and colleagues randomized 20 patients to two infusions of rituximab, 1,000 mg, on days one and 15, and 10 patients to placebo.
All patients were autoantibody positive and had a baseline stimulated whole saliva secretion rate of at least 0.15 mL/min, indicating that they had some residual salivary function.
To minimize infusion-related side effects, patients also were pretreated with intravenous methylprednisolone and had a five-day course of oral prednisone after each infusion.
The mean change in saliva flow was significantly different between the active treatment and placebo groups (P=0.038), the investigators found.
Changes also were seen in laboratory variables. Significant differences in mean change in B-cell count was seen at all time points between weeks five and 48 (P<0.05 for all), and in levels of rheumatoid factor at weeks 12, 24, and 36 (P<0.05 for each).
On the Multidimensional Fatigue Inventory, patients receiving rituximab had decreased scores for reduced activity from baseline to week 36 (P=0.023) and for reduced motivation from baseline to week 12 (P=0.039).
There also were significant improvements in vitality through week 36 (P=0.013).
Patient ratings for nocturnal dry mouth showed improvements at weeks 24, 36, and 48 in the rituximab group, while ratings for ocular dryness improved at weeks 36 and 48.
In the placebo group, significant changes in levels of rheumatoid factor and oral and ocular sicca symptoms were seen only at week five.
The investigators hypothesized that this brief improvement among placebo patients may have been related to the administration of corticosteroids before and after the infusion.
In the rituximab group, the mean number of extraglandular manifestations per patient fell significantly for tendomyalgia at weeks 12 and 36 (P=0.029) and for vasculitis at week 24 (P=0.030).
Among the six patients in the rituximab group who had arthritis at baseline, the symptoms resolved in four, whereas in the placebo group none had arthritis at baseline but three developed symptoms during follow-up.
One patient on rituximab who also had diabetes developed a mild serum-sickness-like disease two weeks after the first infusion, and did not receive a second infusion.
In the rituximab group, 11 patients reported 12 infections, and in the placebo group four patients reported seven infections -- incidence rates that were largely comparable, the researchers wrote.
Rates of infection were 65 per 1,000 patient-years in the rituximab group and 76 per 1,000 patient years in the placebo group.
The rate per 1,000 patient-years in the rituximab group was lower than that reported for patients with rheumatoid arthritis and might be explained by the fact that none of the patients in this study had previous intense immunosuppression as is usually the case for patients with arthritis.
The investigators noted that, in an earlier pilot study, they had observed no improvements in salivary gland function in patients with little or no secretory potential remaining.
They chose 0.15 mL/min as the cutoff for this study because that rate differentiates patients who are still experiencing progressive loss of secretory function and those who have reached end-stage primary Sjgren's syndrome.
"Based on the promising results of this study and our prior study on retreatment with rituximab, which resulted in a beneficial effect comparable with that of the first treatment with this biologic agent, a maintenance therapy with rituximab infusions every six to nine months may be a reasonable approach," they wrote.
Potential advantages for maintenance therapy might be a reduction, and perhaps arrest, of disease progression, along with improvements in quality of life, the researchers noted.
A potential drawback might be unknown long-term adverse effects of repeated B-cell depletion.
"Since primary [Sjgren's syndrome] has a great impact on health-related quality of life, employment, and disability, it is worthwhile to further explore the role of rituximab in a large-size, randomized, controlled trial," the investigators concluded.
The study was supported by Roche.
Statistical analyses were done by an independent contractor, and medical writing assistance was provided by Adelphi Communications, which was supported by Hoffmann-La Roche.
The authors made no declarations regarding financial conflicts of interest.
Primary source: Arthritis & Rheumatism
Source reference:
Meijer J, et al "Effectiveness of rituximab treatment in primary Sjgren's syndrome: a randomized, double-blind, placebo-controlled trial" Arthritis Rheum 2010; 62: 960-68.
By Nancy Walsh, Contributing Writer, MedPage Today
Published: April 06, 2010
Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston and
Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner Earn CME/CE credit
[if: In a small study, the monoclonal antibody rituximab improved the salivary function and other symptoms such as arthritis in patients with Sjgren's syndrome.]
The chimeric monoclonal antibody rituximab (Rituxan) improved both salivary function and the extraglandular manifestations of primary Sjgren's syndrome, a small prospective study found.
Compared with baseline, the stimulated whole saliva flow rate improved significantly among patients given two infusions of rituximab (P=0.018 at week five and P=0.004 at week 12), according to Jiska M. Meijer, MD, and colleagues from the University of Groningen in the Netherlands.
In contrast, patients receiving placebo experienced declines in salivary gland function consistent with the natural history of Sjgren's syndrome, the researchers reported in the April issue of Arthritis & Rheumatism.
The inflammation of the salivary and lacrimal glands seen in this systemic autoimmune disease often is accompanied by extraglandular manifestations including Raynaud's phenomenon, arthritis, and severe fatigue.
B-cell hyperactivity, reflected by elevated levels of rheumatoid factor and other autoantibodies, is a typical finding in Sjgren's syndrome.
No targeted therapies have thus far been made available, but pilot trials of rituximab, which binds to the CD20 surface antigen on B cells, have shown promising improvements in symptoms for six to nine months.
So Meijer and colleagues randomized 20 patients to two infusions of rituximab, 1,000 mg, on days one and 15, and 10 patients to placebo.
All patients were autoantibody positive and had a baseline stimulated whole saliva secretion rate of at least 0.15 mL/min, indicating that they had some residual salivary function.
To minimize infusion-related side effects, patients also were pretreated with intravenous methylprednisolone and had a five-day course of oral prednisone after each infusion.
The mean change in saliva flow was significantly different between the active treatment and placebo groups (P=0.038), the investigators found.
Changes also were seen in laboratory variables. Significant differences in mean change in B-cell count was seen at all time points between weeks five and 48 (P<0.05 for all), and in levels of rheumatoid factor at weeks 12, 24, and 36 (P<0.05 for each).
On the Multidimensional Fatigue Inventory, patients receiving rituximab had decreased scores for reduced activity from baseline to week 36 (P=0.023) and for reduced motivation from baseline to week 12 (P=0.039).
There also were significant improvements in vitality through week 36 (P=0.013).
Patient ratings for nocturnal dry mouth showed improvements at weeks 24, 36, and 48 in the rituximab group, while ratings for ocular dryness improved at weeks 36 and 48.
In the placebo group, significant changes in levels of rheumatoid factor and oral and ocular sicca symptoms were seen only at week five.
The investigators hypothesized that this brief improvement among placebo patients may have been related to the administration of corticosteroids before and after the infusion.
In the rituximab group, the mean number of extraglandular manifestations per patient fell significantly for tendomyalgia at weeks 12 and 36 (P=0.029) and for vasculitis at week 24 (P=0.030).
Among the six patients in the rituximab group who had arthritis at baseline, the symptoms resolved in four, whereas in the placebo group none had arthritis at baseline but three developed symptoms during follow-up.
One patient on rituximab who also had diabetes developed a mild serum-sickness-like disease two weeks after the first infusion, and did not receive a second infusion.
In the rituximab group, 11 patients reported 12 infections, and in the placebo group four patients reported seven infections -- incidence rates that were largely comparable, the researchers wrote.
Rates of infection were 65 per 1,000 patient-years in the rituximab group and 76 per 1,000 patient years in the placebo group.
The rate per 1,000 patient-years in the rituximab group was lower than that reported for patients with rheumatoid arthritis and might be explained by the fact that none of the patients in this study had previous intense immunosuppression as is usually the case for patients with arthritis.
The investigators noted that, in an earlier pilot study, they had observed no improvements in salivary gland function in patients with little or no secretory potential remaining.
They chose 0.15 mL/min as the cutoff for this study because that rate differentiates patients who are still experiencing progressive loss of secretory function and those who have reached end-stage primary Sjgren's syndrome.
"Based on the promising results of this study and our prior study on retreatment with rituximab, which resulted in a beneficial effect comparable with that of the first treatment with this biologic agent, a maintenance therapy with rituximab infusions every six to nine months may be a reasonable approach," they wrote.
Potential advantages for maintenance therapy might be a reduction, and perhaps arrest, of disease progression, along with improvements in quality of life, the researchers noted.
A potential drawback might be unknown long-term adverse effects of repeated B-cell depletion.
"Since primary [Sjgren's syndrome] has a great impact on health-related quality of life, employment, and disability, it is worthwhile to further explore the role of rituximab in a large-size, randomized, controlled trial," the investigators concluded.
The study was supported by Roche.
Statistical analyses were done by an independent contractor, and medical writing assistance was provided by Adelphi Communications, which was supported by Hoffmann-La Roche.
The authors made no declarations regarding financial conflicts of interest.
Primary source: Arthritis & Rheumatism
Source reference:
Meijer J, et al "Effectiveness of rituximab treatment in primary Sjgren's syndrome: a randomized, double-blind, placebo-controlled trial" Arthritis Rheum 2010; 62: 960-68.