Epratuzumab, Targeting CD-22, Shows Promise

PARIS — The anti-CD22 monoclonal antibody epratuzumab showed promise as a targeted therapy for systemic lupus erythematosus in two small studies, providing improvements in disease activity and health-related quality of life.

B cells play a central role in the pathogenesis of systemic lupus erythematosus (SLE), and a new potential therapeutic target is CD22, which is a glycoprotein present on the surface of B cells.

Unlike rituximab, which acts by depleting B cells, epratuzumab acts through regulating the activation of B cells and their interactions with T cells, Dr. Vibeke B. Strand reported at the annual European Congress of Rheumatology.

In all, 90 patients with severe SLE were randomized to receive placebo or epratuzumab in infusions of 360 mg/m

All patients had antinuclear antibody (ANA)-positive disease and had experienced a severe (grade A) or moderate (grade B) British Isles Lupus Assessment Group (BILAG) flare. Stable doses of corticosteroids, immunosuppressants, and antimalarial drugs were permitted.

The two studies were initiated in 2005 but recruitment and dosing were discontinued prematurely in September 2006 because of an interruption in the drug supply. Patients continued to be followed, however, and the available data have now been analyzed.

At the time of study discontinuation, 29% of the intent-to-treat population had received all infusions over the entire 48-week period, and 91% had received at least four infusions.

Health-related quality of life was assessed using the Medical Outcomes Study short form-36 (SF-36), which evaluates physical functioning, pain, general health, vitality, social functioning, and mental health.

The treatment groups were comparable at baseline: Mean age was 37 years, mean body weight was 69 kg, 94% were female, and 67% were white.

Overall, patients had high disease activity, with 43% having one or more BILAG grade A flare; the mean total BILAG score was 13.2, according to Dr. Strand of Stanford (Calif.) University.

Burden of disease was also high, as shown by baseline scores on the physical and mental components of the SF-36 that were 1.5–2.0 and 0.6–1.2 standard deviations lower, respectively, than age and sex-matched controls and patients in previously reported SLE trials, she noted.

In all, 63% were receiving immunosuppressive drugs, 71% were receiving antimalarials, and 43% were being treated with doses of prednisone exceeding 25 mg/day at baseline.

By week 48, total BILAG scores in the epratuzumab groups were reduced to 6.3 from 13.2 at baseline, compared with reductions to 8.6 from 13.2 in the placebo group, Dr. Strand wrote.

“Although most patients did not receive full treatment courses and sample sizes were small, epratuzumab treatment resulted in clinically meaningful improvements in health-related quality of life,” she concluded.

In a separate poster that also analyzed data from the two preliminary studies, Dr. Daniel Wallace of the University of California, Los Angeles, reported that cumulative corticosteroid use over 24 weeks—adjusted for race, baseline medications, and baseline differences—was lower in the epratuzumab groups.

At week 24, 24 (75%) patients receiving the 360-mg dose and 6 (100%) of those receiving the 720-mg dose were able to taper their corticosteroids, compared with 13 (57%) of those receiving placebo, according to Dr. Wallace.

Cumulative exposure to steroids was lower in the active treatment groups, with a least squares mean difference from placebo at 24 weeks of −1,051 mg and −1,973 mg for the 360-mg and 720-mg groups, respectively.

The incidence of treatment-emergent adverse events was similar in the active and placebo groups, with serious adverse events occurring in 30%, 25%, and 36% of patients in the placebo, 360-mg, and 720-mg groups, respectively, reported Dr. Wallace.

Serious infections occurred in 18% of the epratuzumab groups and in 22% of the placebo group.

Adverse events leading to discontinuation occurred in three patients in the placebo group and in three patients in the 720-mg group.

The manufacturer of epratuzumab, UCB Inc., has now initiated another pair of phase IIB trials, with the primary objective of determining the dose response and frequency.

Dr. Strand has disclosed receiving consulting fees from UCB.

ELSEVIER GLOBAL MEDICAL NEWS

PARIS — The anti-CD22 monoclonal antibody epratuzumab showed promise as a targeted therapy for systemic lupus erythematosus in two small studies, providing improvements in disease activity and health-related quality of life.

B cells play a central role in the pathogenesis of systemic lupus erythematosus (SLE), and a new potential therapeutic target is CD22, which is a glycoprotein present on the surface of B cells.

Unlike rituximab, which acts by depleting B cells, epratuzumab acts through regulating the activation of B cells and their interactions with T cells, Dr. Vibeke B. Strand reported at the annual European Congress of Rheumatology.

In all, 90 patients with severe SLE were randomized to receive placebo or epratuzumab in infusions of 360 mg/m

All patients had antinuclear antibody (ANA)-positive disease and had experienced a severe (grade A) or moderate (grade B) British Isles Lupus Assessment Group (BILAG) flare. Stable doses of corticosteroids, immunosuppressants, and antimalarial drugs were permitted.

The two studies were initiated in 2005 but recruitment and dosing were discontinued prematurely in September 2006 because of an interruption in the drug supply. Patients continued to be followed, however, and the available data have now been analyzed.

At the time of study discontinuation, 29% of the intent-to-treat population had received all infusions over the entire 48-week period, and 91% had received at least four infusions.

Health-related quality of life was assessed using the Medical Outcomes Study short form-36 (SF-36), which evaluates physical functioning, pain, general health, vitality, social functioning, and mental health.

The treatment groups were comparable at baseline: Mean age was 37 years, mean body weight was 69 kg, 94% were female, and 67% were white.

Overall, patients had high disease activity, with 43% having one or more BILAG grade A flare; the mean total BILAG score was 13.2, according to Dr. Strand of Stanford (Calif.) University.

Burden of disease was also high, as shown by baseline scores on the physical and mental components of the SF-36 that were 1.5–2.0 and 0.6–1.2 standard deviations lower, respectively, than age and sex-matched controls and patients in previously reported SLE trials, she noted.

In all, 63% were receiving immunosuppressive drugs, 71% were receiving antimalarials, and 43% were being treated with doses of prednisone exceeding 25 mg/day at baseline.

By week 48, total BILAG scores in the epratuzumab groups were reduced to 6.3 from 13.2 at baseline, compared with reductions to 8.6 from 13.2 in the placebo group, Dr. Strand wrote.

“Although most patients did not receive full treatment courses and sample sizes were small, epratuzumab treatment resulted in clinically meaningful improvements in health-related quality of life,” she concluded.

In a separate poster that also analyzed data from the two preliminary studies, Dr. Daniel Wallace of the University of California, Los Angeles, reported that cumulative corticosteroid use over 24 weeks—adjusted for race, baseline medications, and baseline differences—was lower in the epratuzumab groups.

At week 24, 24 (75%) patients receiving the 360-mg dose and 6 (100%) of those receiving the 720-mg dose were able to taper their corticosteroids, compared with 13 (57%) of those receiving placebo, according to Dr. Wallace.

Cumulative exposure to steroids was lower in the active treatment groups, with a least squares mean difference from placebo at 24 weeks of −1,051 mg and −1,973 mg for the 360-mg and 720-mg groups, respectively.

The incidence of treatment-emergent adverse events was similar in the active and placebo groups, with serious adverse events occurring in 30%, 25%, and 36% of patients in the placebo, 360-mg, and 720-mg groups, respectively, reported Dr. Wallace.

Serious infections occurred in 18% of the epratuzumab groups and in 22% of the placebo group.

Adverse events leading to discontinuation occurred in three patients in the placebo group and in three patients in the 720-mg group.

The manufacturer of epratuzumab, UCB Inc., has now initiated another pair of phase IIB trials, with the primary objective of determining the dose response and frequency.

Dr. Strand has disclosed receiving consulting fees from UCB.

ELSEVIER GLOBAL MEDICAL NEWS

PARIS — The anti-CD22 monoclonal antibody epratuzumab showed promise as a targeted therapy for systemic lupus erythematosus in two small studies, providing improvements in disease activity and health-related quality of life.

B cells play a central role in the pathogenesis of systemic lupus erythematosus (SLE), and a new potential therapeutic target is CD22, which is a glycoprotein present on the surface of B cells.

Unlike rituximab, which acts by depleting B cells, epratuzumab acts through regulating the activation of B cells and their interactions with T cells, Dr. Vibeke B. Strand reported at the annual European Congress of Rheumatology.

In all, 90 patients with severe SLE were randomized to receive placebo or epratuzumab in infusions of 360 mg/m

All patients had antinuclear antibody (ANA)-positive disease and had experienced a severe (grade A) or moderate (grade B) British Isles Lupus Assessment Group (BILAG) flare. Stable doses of corticosteroids, immunosuppressants, and antimalarial drugs were permitted.

The two studies were initiated in 2005 but recruitment and dosing were discontinued prematurely in September 2006 because of an interruption in the drug supply. Patients continued to be followed, however, and the available data have now been analyzed.

At the time of study discontinuation, 29% of the intent-to-treat population had received all infusions over the entire 48-week period, and 91% had received at least four infusions.

Health-related quality of life was assessed using the Medical Outcomes Study short form-36 (SF-36), which evaluates physical functioning, pain, general health, vitality, social functioning, and mental health.

The treatment groups were comparable at baseline: Mean age was 37 years, mean body weight was 69 kg, 94% were female, and 67% were white.

Overall, patients had high disease activity, with 43% having one or more BILAG grade A flare; the mean total BILAG score was 13.2, according to Dr. Strand of Stanford (Calif.) University.

Burden of disease was also high, as shown by baseline scores on the physical and mental components of the SF-36 that were 1.5–2.0 and 0.6–1.2 standard deviations lower, respectively, than age and sex-matched controls and patients in previously reported SLE trials, she noted.

In all, 63% were receiving immunosuppressive drugs, 71% were receiving antimalarials, and 43% were being treated with doses of prednisone exceeding 25 mg/day at baseline.

By week 48, total BILAG scores in the epratuzumab groups were reduced to 6.3 from 13.2 at baseline, compared with reductions to 8.6 from 13.2 in the placebo group, Dr. Strand wrote.

“Although most patients did not receive full treatment courses and sample sizes were small, epratuzumab treatment resulted in clinically meaningful improvements in health-related quality of life,” she concluded.

In a separate poster that also analyzed data from the two preliminary studies, Dr. Daniel Wallace of the University of California, Los Angeles, reported that cumulative corticosteroid use over 24 weeks—adjusted for race, baseline medications, and baseline differences—was lower in the epratuzumab groups.

At week 24, 24 (75%) patients receiving the 360-mg dose and 6 (100%) of those receiving the 720-mg dose were able to taper their corticosteroids, compared with 13 (57%) of those receiving placebo, according to Dr. Wallace.

Cumulative exposure to steroids was lower in the active treatment groups, with a least squares mean difference from placebo at 24 weeks of −1,051 mg and −1,973 mg for the 360-mg and 720-mg groups, respectively.

The incidence of treatment-emergent adverse events was similar in the active and placebo groups, with serious adverse events occurring in 30%, 25%, and 36% of patients in the placebo, 360-mg, and 720-mg groups, respectively, reported Dr. Wallace.

Serious infections occurred in 18% of the epratuzumab groups and in 22% of the placebo group.

Adverse events leading to discontinuation occurred in three patients in the placebo group and in three patients in the 720-mg group.

The manufacturer of epratuzumab, UCB Inc., has now initiated another pair of phase IIB trials, with the primary objective of determining the dose response and frequency.

Dr. Strand has disclosed receiving consulting fees from UCB.

ELSEVIER GLOBAL MEDICAL NEWS