36 Autoimmunity/Connective Tissue S KIN & ALLERGY N EWS • December 2007 Belimumab Benefits Seen in Lupus, Analysis Shows

ARTICLES BY NANCY WALSH in Lupus Erythematosus National Assessment (SELENA) were serologically active at baseline was 46%, which is New York Bureau at 24 weeks—was not met. highly statistically significant at 52 weeks compared to a The study included 449 patients with lupus who were response rate of 29% with placebo,” said Dr. Ginzler, who B ARCELONA — Significant improvements in disease randomized to receive placebo or belimumab in doses of is professor of medicine and chief of rheumatology, State activity were observed among lupus patients treated with 1, 4, or 10 mg/kg on days 0, 14, 28, and then monthly for University of New York, Brooklyn. belimumab in a new analysis of data from an earlier 52 weeks. By week 76 the response rate had risen to 56%. study using a combined response end point, Dr. Ellen The study continued in open-label fashion through At baseline, the mean SELANA-SLEDAI score was 9.6. Ginzler said at the annual European Congress of week 76. Patients in the active treatment groups had 29% and 38% Rheumatology. A subsequent analysis, however, reductions in SELENA-SLEDAI scores at weeks 52 and 76, The analysis used an evidence- A single index determined that significant bene- respectively. based combined response end cannot fits were seen at 52 weeks among At week 52 the belimumab-treated patients had fewer point that has been developed to adequately the 72% of patients who were shifts to worse scores in three of the eight BILAG organ improve the assessment of re- assess treatment serologically active at baseline, systems: musculoskeletal, neurologic, and cardiovascular- sponses to drug intervention in response in this with titers of antinuclear anti- respiratory. clinical trials for systemic lupus heterogeneous body of 1:80 or greater and/or Patients who were classified as responders on the com- erythematosus. disease. titers of anti-double-stranded posite end point also had greater reductions in activated “The heterogeneity of lupus dis- (ds) DNA of 30 IU or greater B cells and anti-ds DNA antibodies, along with greater im- ease manifestations contributes to DR. GINZLER (Arthritis Rheum. 2006;54[suppl. provements in the SF-36. the difficulty of using a single index 9]:S258). Combining multiple disease activity measures into a re- to adequately assess therapeutic response,” Dr. Ginzler Responses among this cohort have now been analyzed sponse end point improved the assessment of variable dis- explained. according to the new combined response end point, ease activity and was predictive of biomarker and quali- Belimumab (LymphoStat-B) is a monoclonal anti- which defines efficacy as an improvement in SELENA- ty of life improvements, Dr. Ginzler said. body that binds with high specificity to B lymphocyte SLEDAI of four points or more and a British Isles Lupus “This combined end point has now been accepted by stimulator (BLyS), which, being a potent costimulator Assessment Group (BILAG) score that reflects the num- regulatory authorities and is being used in two global of B cells, is thought to play a role in B-cell–mediated ber and severity of organ system flares. phase III studies of belimumab that have recently begun autoimmunity. The combined end point also reflects physician’s glob- enrollment,” she said. In the original analysis of the study results, the prima- al assessment and patient health-related quality of life as The studies are being sponsored by Human Genome Sci- ry end point—reduction in disease activity as measured evaluated on the Short Form (SF)-36. ences, Inc., manufacturer of LymphoStat-B, and Glaxo- by the Systemic Lupus Erythematosus Disease Activity “Using this combined outcome efficacy measure, the SmithKline. Dr. Ginzler has previously disclosed receiving Index (SLEDAI) as modified for the Safety of Estrogens response to belimumab therapy among patients who research grants from Human Genome Sciences. ■ Persistent Proteinuria in B-Cell Depletion With Rituximab SLE Predicts Renal Relapse Appears Promising for Myopathies

B ARCELONA — Factors that were do reported in a poster presentation. B ARCELONA — Clinical improvement in sence of CD20+ B cells. This patient’s Dis- predictive of relapse in lupus nephritis Induction therapies included corti- a small series of patients with inflammato- ease Activity Score–28 (DAS28) score fell after induction therapy were persis- costeroids alone in 23% of patients, cor- ry myopathies treated with rituximab sug- from 6.8 to 4.5 after 3 months, according to tence of proteinuria and abnormal C4 ticosteroids plus cyclophosphamide in gests that B-cell depletion may prove useful Dr. Blom. levels, and patients having received cy- 65%, azathioprine in 10%, and my- in these disorders, according to Dr. Marlies After initial good response, three patients clophosphamide for less than 2 years, cophenolate mofetil in 2%. Mean du- Blom of the department of rheumatology, required retreatment for exacerbations of Dr. Eva Salgado reported at the annual ration of induction therapy was 27 Radboud University Nijmegen (the Nether- myositis at about 6 months. European Congress of Rheumatology. months. lands) Medical Centre. No serious adverse events were observed Considerable variability is seen in A total of 71% of patients showed a Among seven patients with and immunoglobulin levels re- the clinical course and response to ther- complete response to induction thera- dermatomyositis, polymyosi- Among seven mained within normal levels. apy in patients with systemic lupus py, while 24% had a partial response tis, or antisynthetase syn- patients, two These results suggest that B erythematosus (SLE) who develop and 5% did not respond. drome, two infusions of cells play an important role in nephritis, and it would be useful to After the initial response, 59% re- 1,000 mg rituximab 2 weeks infusions of the pathogenesis of inflam- identify factors that are associated with ceived maintenance therapy with anti- apart resulted in a mean 30% 1,000 mg matory myopathies, Dr. Blom relapse so that more aggressive treat- malarial drugs, azathioprine, or both. increase in muscle strength at noted. ment could be used from the outset, ex- During a mean of 13 years of follow- 3 months, Dr. Blom reported rituximab Another recent report sug- plained Dr. Salgado of Hospital 12 de up, 34 patients experienced renal re- in a poster session at the an- 2 weeks apart gested that a possible ratio- Octubre, Madrid. lapse, at a mean of 51 months after the nual European Congress of nale for considering B-cell de- A study was therefore conducted that end of induction therapy. Rheumatology. resulted in a pletion as a therapeutic included all 128 patients diagnosed with Multivariate analysis found that re- Patients’ subjective reports mean 30% strategy in dermatomyositis SLE and nephritis in the rheumatology lapse was independently associated of improvement in muscle was that treatment with rit- department of Dr. Salgado’s hospital with persistence of abnormal C4 levels strength were confirmed by increase in uximab had previously been between 1977 and 2007. or residual proteinuria greater than 0.5 handheld dynamometry. muscle strength. shown to result in improve- A total of 114 of the patients were g/day after the completion of induc- The patients ranged in age ments in muscle strength in women, and more than 95% were tion therapy, and duration of cy- from 38 to 58 years, and the duration of humorally mediated autoimmune periph- white. Mean age at the appearance of clophosphamide therapy for less than 2 their disease ranged from 3 to 16 years. Four eral neuropathies (Arthritis Rheum. nephritis was 30 years, and mean time years, according to Dr. Salgado. of the seven were female. 2005;52:601-7). from the diagnosis of SLE was 2 years. Factors that were not predictive of Previous treatments included oral and The importance of humoral immunity in Renal biopsy at the time of diagno- relapse included histologic findings, intravenous prednisone, methotrexate, dermatomyositis also is suggested by the sis of nephritis showed minimal age at SLE or nephritis diagnosis, de- azathioprine, cyclophosphamide, interfer- observation that perifascicular endothelial changes in 2%, mesangial glomeru- lay in induction therapy, use of main- on, etanercept, and intravenous im- immunoglobulin and complement deposi- lonephritis in 18%, focal proliferative tenance therapy, or other clinical char- munoglobulin. tion are thought to result in the muscle is- glomerulonephritis in 12%, diffuse pro- acteristics. A mean 13% improvement was reported chemia and atrophy (J. Rheumatol. liferative glomerulonephritis in 55%, Six patients developed end-stage re- on Health Assessment Questionnaire 2006;33:1021-6). and membranous glomerulonephritis nal failure and 14 died. Relapse was (HAQ) scores, and improvements also were Furthermore, the observation that there in 13%. predictive of long-term renal failure seen in levels of creatine phosphokinase, a are antibodies specific for myositis also sup- At the time of initiation of induc- but was not associated with increased marker of disease activity. ports the concept of B-cell–mediated hu- tion therapy, 29 patients had some de- mortality in this group of patients, Dr. In one patient, a muscle biopsy taken 4 moral abnormality in dermatomyositis gree of creatinine increase, Dr. Salga- Salgado observed. ■ months after treatment showed a total ab- (Medicine [Baltimore] 1991;70:360-74). ■

Pages 36a—36bŅ