Pulsed suppressive treatment in rheumatoid arthritis: intravenous methylprednisolone and nitrogen mustard

Persistent polyarticular rheumatoid arthritis (RA) and aggressive disease flares resistant to conventional therapy can effectively be controlled by intravenous pulse methylprednisolone (IVMP) or nitrogen mustard (HN2). The efficacy, toxicity and immunologic effects of each agent are reviewed. Clinical response is evident within days of the start of therapy for both; persisting up to 6 weeks for IVMP and at least 59 days for HN2. Morbidity from both agents is minimal when appropriate precautions are taken. No mortalities directly related to either modality have been reported in RA.     

High-dose intravenous methylprednisolone pulse therapy in systemic lupus erythematosus

To determine guidelines for treatment with high-dose intravenous methylprednisolone in lupus nephritis, we prospectively assessed the response to pulse therapy in 34 patients. In 12 of them, serum creatinine decreased by at least 20 percent within two months of treatment whereas in the remaining 22 there was no such response. Patients who responded were characterized by recent deterioration in function whereas nonresponders had had a more stable antecedent course (p = 0.003). Responders also had more diffuse lesions on renal biopsy (p = 0.028), had higher levels of anti-DNA antibodies (p < 0.05), and tended to have higher tilers of immune complexes and lower total hemolytic complement.High-dose intravenous methylprednisolone therapy may lead to striking improvement in renal function in lupus nephritis, especially in the subset of patients with recent antecedent functional deterioration. This improvement was maintained in 60 percent of the patients who responded for at least six months.     

Combination therapy with pulsed methylprednisolone in rheumatoid arthritis.

Pulsed methylprednisolone (PMP) has been shown to produce clinical improvement and reduction in the ESR and acute phase protein concentrations in patients with active rheumatoid arthritis and has been advocated for use either as an alternative to slow-acting antirheumatoid drugs (SAARDs) or in conjunction with SAARDs to accelerate the response to treatment. To test these potential roles for PMP 45 patients with active RA were randomly allocated to treatment with PMP alone, PMP + sulphasalazine (SAS - at a maintenance dose of 2.0 g/day), or PMP + D-penicillamine (DPA - at a maintenance dose of 500 mg/day). In each case three 1 g intravenous infusions were given on alternate days during the first week of the trial. Patients were monitored for 24 weeks by standard clinical and laboratory measurements. All three treatment groups showed significant clinical and laboratory improvements at two weeks. With PMP + DPA and PMP + SAS these improvements were sustained and were not significantly different in these two treatment groups. However, in the 'PMP only' group ESR and CRP rose to pretreatment values by eight weeks. Twelve patients withdrew from the study owing to a relapse of the RA. No serious adverse effects were seen in the 'PMP only' group. Both combination regimens were well tolerated; adverse effects seen were attributable to either DPA or SAS. We conclude that PMP alone is insufficient for treatment of RA but can be used successfully in combination with either DPA or SAS. A comparison between these results obtained from two previous groups of 15 patients treated with DPA alone and SAS alone (using the same study design) shows that PMP accelerated the response to therapy by at least six weeks.     

High-dose intravenous methylprednisolone for acute childhood idiopathic thrombocytopenic purpura

49 children with acute idiopathic thrombocytopenic purpura (ITP) were divided into non-treatment, oral prednisone (2 mg/kg), and high-dose intravenous methylprednisolone (HIVMP) treatment groups which consisted of 17, 16 and 16 children respectively. Platelet counts rose above 150,000/microliters over a 2-week period in 5 (29.4%) children in the first group, 5 (31.2%) in the second group and 15 (93.7%) children in the third group. Platelet counts reached the normal level in only 3 days in 11 (68.7%) children treated with HIVMP. Initially, antiplatelet antibodies (APA) were shown by the Handin and Stossel method in every patient. With normalization of platelet counts, the antibodies decreased but could still be detected in every case; antibody decrease was greater in the HIVMP group. With the exception of mild cushingoid appearance, none of the major corticosteroid side effects was observed in the treated children.     

Bone metabolism during methylprednisolone pulse therapy in rheumatoid arthritis.

The deleterious effects of corticosteroids (CS) on bone are well known, but probably differ depending on duration and dosage of CS therapy. Presently huge amounts of CS are given over a short period of time in different rheumatic conditions. Not much is known about the effect of this kind of CS treatment on bone metabolism. Twenty patients with persistently active rheumatoid arthritis were treated with 1 g methylprednisolone (MP) three times on alternate days over a five day period. Twenty four hours after the first MP pulse serum calcium was increased and the values of parathyroid hormone and 1,25-dihydroxyvitamin D tended to increase. After the second MP pulse, however, these values had returned to the starting values. The urinary calcium excretion increased during MP pulse therapy and returned to the initial value immediately after the pulse therapy. The hydroxyproline excretion tended to decrease during therapy and stayed decreased immediately afterwards, indicating a decrease in bone resorption. It is concluded that bone metabolism is not seriously affected during MP pulse therapy.     

High-dose intravenous methylprednisolone therapy associated with osteonecrosis in patients with systemic lupus erythematosus.

Osteonecrosis is related to the use of steroids in patients with systemic lupus erythematosus (SLE); its association with the use of 'pulses' of methylprednisolone (PMP) is not clear at present. In a retrospective analysis of 190 patients with SLE we found that 19% of 36 patients treated with PMP had osteonecrosis compared with 6% of 154 patients without that treatment (P < 0.04). Risk factors associated with osteonecrosis were PMP treatment, cushingoid appearance, steroid doses > or = 40 mg/day during the first month of treatment, a ratio of steroid dose in grams/year > or = 12, hematuria and proteinuria. In a stepwise regression model, when cushingoid appearance was excluded, PMP became the only significant factor (P = 0.045). We conclude that osteonecrosis can be considered a long-term complication of PMP treatment in SLE patients.     

Intravenous regional administration of methylprednisolone in rheumatoid arthritis

Summary Intravenous regional administration of corticosteroid (IVRAS) in the treatment of rheumatoid arthritis of the hand has not been reported previously. The method is based on a modification of Bier's block, with substitution of corticosteroid for local anaesthetic. Twenty-two patients were assessed in this double-blind, placebo-controlled study. The technique was safe and effective in improving grip strength, with a group mean improvement of more than 50%. Because suppression of endogenous cortisol production 24 h after treatment was commensurate with the dose of methylprednisolone used (40 mg), we could not exclude that the response may have been due to systemic steroid. Further studies are required to define the real value of IVRAS as it may offer alternative treatment of the joints and tendons within the hand and wrist in some patients rather than more prolonged oral therapy or individual, multiple joint or sheath injections.     

大剂量环磷酰胺治疗难治性类风湿关节炎初探

目的：研究大剂量化疗（high-dose chemotherapy,HDC)治疗难治性类风湿关节炎（RA）的可行性，有效性及安全性。方法：对4例常规治疗效果不佳的难治性RA患者进行大剂量环磷酰胺（CTX）治疗，用量为80-100mg/kg，总量4－5g分2－3d给药，观察此4例患者治疗前后的临床转归和实验室改变，并进行相关文献复习。结果：4例难治性RA患者经HDC后，2例随访12个月，2例随访6个月，RA活动指数均明显下降，达ACR50标准病情缓解，且4例患者均对大剂量CTX耐受性良好，无严重不良反应发生，结论：HDC对此4例难治性RA的治疗安全，可行，且临床症状完全缓解，但如何选择合适的病例尚待进一步探讨，HDC能否使病情长期缓解尚有待于更样本的临床病例观察及便长时间的临床随访。