Lockwood C M
University of Cambridge, School of Clinical Medicine, Addenbrooke's Hospital.
J R Coll Physicians Lond. 1998 Sep-Oct;32(5):473-8.
Humanised monoclonal antibodies are immunomodulatory tools with high specificity and sustained therapeutic potential. We investigated the effectiveness of treatment with monoclonal antibodies to lymphocyte CD52 and CD4 in patients with Wegener's granulomatosis that had proved intractable despite conventional treatment. We also investigated whether repeated courses of monoclonal antibody treatment alone could be used to control relapses in patients in remission.
We studied 17 consecutive patients with refractory Wegener's granulomatosis seen between June 1992 and June 1996. In all patients, treatment with prednisolone and cyclophosphamide or azathioprine for at least six months had been unsuccessful, and all were followed up for at least six months after monoclonal antibody treatment. Diagnosis was established on clinical, serological and histological criteria. Disease activity in the upper airways, lungs or kidneys at referral was documented by whole-body scintiscanning, computed tomography, or isotope measurement of the glomerular filtration rate, as well as by tissue biopsy, where appropriate. Monoclonal antibodies to CD52 followed by CD4 were given intravenously in courses lasting five days each.
Remission (programmed withdrawal of drug treatment with no return of refractory disease) was obtained in 16 patients after one course of CD52 +/- CD4, and confirmed by serial studies of abnormalities found before treatment. In one patient, disease remained unchecked. In responders, cytotoxic drugs were stopped during monoclonal antibody treatment and were not used again, while steroids were tapered off gradually. Disease relapses occurred in nine. Monoclonal antibodies alone controlled these during follow-up that totalled 30 patient years. Neither systemic opportunistic infection nor lymphoma development complicated this regimen.
Monoclonal antibody treatment may be better and safer for diseases, such as Wegener's granulomatosis, that require long-term cytotoxic and steroid treatment because it speeds remission and avoids the iatrogenic complications of cumulative drug toxicity.
人源化单克隆抗体是具有高特异性和持续治疗潜力的免疫调节工具。我们研究了针对淋巴细胞CD52和CD4的单克隆抗体治疗对尽管接受了传统治疗但仍难治的韦格纳肉芽肿患者的有效性。我们还研究了单独重复使用单克隆抗体治疗疗程是否可用于控制缓解期患者的复发。
我们研究了1992年6月至1996年6月期间连续收治的17例难治性韦格纳肉芽肿患者。所有患者接受泼尼松龙和环磷酰胺或硫唑嘌呤治疗至少6个月均未成功，且在接受单克隆抗体治疗后均随访至少6个月。根据临床、血清学和组织学标准进行诊断。转诊时上呼吸道、肺部或肾脏的疾病活动情况通过全身闪烁扫描、计算机断层扫描或肾小球滤过率的同位素测量以及必要时的组织活检记录。针对CD52随后针对CD4的单克隆抗体静脉给药，每个疗程持续5天。
16例患者在接受一个疗程的CD52+/-CD4治疗后获得缓解（药物治疗计划停药且难治性疾病未复发），并通过对治疗前发现的异常进行系列研究得到证实。1例患者疾病仍未得到控制。在缓解者中，细胞毒性药物在单克隆抗体治疗期间停用且未再次使用，而类固醇逐渐减量。9例出现疾病复发。在总计30患者年的随访期间，单独使用单克隆抗体控制了这些复发。该治疗方案未并发全身性机会性感染或淋巴瘤。
对于诸如韦格纳肉芽肿等需要长期细胞毒性和类固醇治疗的疾病，单克隆抗体治疗可能更好且更安全，因为它能加速缓解并避免累积药物毒性的医源性并发症。
