To observe the efficacy and safety of 2 consecutive cycles of high-dose dexamethasone in adult patients with newly diagnosed primary immune thrombocytopenia (ITP). Methods Fifty-nine patients with newly diagnosed ITP were randomly divided into two groups: 30 patients in the dexamethasone treatment group were treated with dexamethasone 40 mg/d orally in two doses for 4 d. After 7 d, another cycle was repeated, and no maintenance treatment was given thereafter; 29 patients in the prednisone group were treated with 1.0-1.5 mg kg-1 d-1 orally for 4 weeks and then the dose was gradually reduced. The immediate and long-term efficacy and safety were observed between the two groups.
Results: The efficiency of the dexamethasone group was significantly higher than that of the prednisone group at the first and second weeks after treatment (50.0% vs. 24.1%, 73.3% vs. 55.2%, P-value <0.01 and 0.05, respectively), and the efficiency at the third week after treatment was still higher than that of the prednisone group, but the difference was not statistically significant (83.3% vs. 68.9%, P>0.05). Long-term efficacy: At the 3rd month of follow-up, the recurrence rate in the dexamethasone group was not statistically different from that in the prednisone group except for the 1st month (16.0 vs. 20.0%, p>0.05), and the recurrence rate in the 2nd and 3rd months was significantly lower in the dexamethasone group than in the prednisone group (24.0% vs. 40.0% and 32.0% vs. 65.0%, p-values <0.05 and 0.01, respectively). The adverse effects in the dexamethasone group were mild, and there was no one case of complicated infection or Cushing's disease. Conclusion The near- and long-term efficacy of high-dose dexamethasone in the treatment of ITP was better than that of conventional dose prednisone and had a good safety profile.
Primary immune thrombocytopenia is an immune-mediated autoimmune disease characterized by thrombocytopenia, which is the most common clinical bleeding disorder and accounts for about 1/3 of bleeding disorders. Prednisone is the drug of choice for the traditional treatment of ITP and is effective in about 60% of patients, but its long-term application is likely to lead to adverse effects. However, long-term application is prone to adverse effects and is prone to recurrence when the dose is reduced or discontinued. Therefore, there is a need to explore safer and more effective treatment options. In recent years, high-dose dexamethasone has been used to treat ITP with good efficacy, and it is recommended for first-line treatment of ITP by both domestic and international guidelines or expert consensus. In this study, we compared the efficacy and safety of 2 consecutive cycles of high-dose dexamethasone with conventional doses of prednisone in the treatment of newly diagnosed adult ITP using a randomized method, and the results are reported below.
Subjects and methods
1. General data: 59 patients with newly diagnosed adult ITP who were outpatients and inpatients in the Department of Hematology of our hospital from November 2008 to June 2010 were selected, and all of them met the literature criteria. Among them, 21 cases were male and 38 cases were female, with a median age of 31(16~65) years. Inclusion criteria: platelets <30×109 or with active bleeding. Exclusion criteria.
(1) patients with refractory or relapsed ITP.
(2) Combined refractory hypertension, severe diabetes, epilepsy, peptic ulcer and bleeding, severe infection, pregnancy, etc. 59 patients were randomly divided into 2 groups, 30 in the dexamethasone group and 29 in the prednisone group. The differences in gender, age and clinical characteristics between the two groups were not statistically significant (Table 1, all P values > 0.05).
2. Treatment: The dexamethasone group received 40 mg/d of dexamethasone orally in 2 doses for 4 d. The treatment was repeated for 1 cycle at 1-week intervals, with no further maintenance treatment. The prednisone group was treated with the conventional dose of prednisone, i.e., 1-1.5 mg/kg orally daily for 4 weeks and then tapered to the minimum maintenance dose or discontinued. Proton pump inhibitors were given to prevent stress ulcers during treatment in both groups, and platelet suspension was transfused as appropriate for those with active bleeding before treatment.
3, efficacy assessment criteria: complete remission (CR): platelet count >100×109/L after treatment and no bleeding performance; effective (R): platelet count >30×109/L after treatment and 2 times more than the basal platelet count, and no bleeding performance; ineffective (NR): platelet count <30×109/L after treatment or platelet count increased by less than 2 times the basal value or with bleeding manifestation. Anyone who met CR and R was considered effective. Relapse: After obtaining CR, R, the platelet count drops below 30×109/L again or there are bleeding symptoms.
4. Observation of adverse reactions.
(1) Observe the occurrence of nausea, vomiting, abdominal distension, diarrhea, dizziness, drowsiness and other symptoms;
(2) Observe the occurrence of Cushing’s syndrome;
(3) Detect blood pressure; detect blood potassium, blood glucose, liver and kidney function.
5. Statistical treatment: SAS9.0 statistical software was used for statistical analysis, and the comparison of efficiency and recurrence rate was performed by 2 test. (P < 0.05) indicated that the difference was statistically significant.
Results
1, recent efficacy The blood routine was rechecked at the 1st, 2nd and 3rd week after treatment, and the efficiency of ITP treatment in the 2 groups of programs. The results showed that the efficiency of the dexamethasone group was significantly higher than that of the prednisone group at weeks 1 and 2 after treatment (P<0.05), and the dexamethasone group was still higher than the prednisone group at week 3, but the difference was not statistically significant (P>0.05). Dexamethasone had a rapid onset of action, with most effective patients achieving remission within 1 week.
2. Long-term efficacy: The recurrence rate of effective patients in the two groups at the 1st, 2nd and 3rd months after treatment was compared in Table 3, except that there was no significant difference in the recurrence rate between the two groups at the 1st month of follow-up (P>0.05), and the recurrence rate of patients in the dexamethasone group at the 2nd and 3rd months was significantly lower than that in the prednisone group (P<0.05).
3, Adverse effects: Patients in the dexamethasone group tolerated the treatment well, and abdominal distension, nausea, hypertension and hyperglycemia appeared briefly and returned to normal after the completion of treatment. There was no one case of complicated infection and Cushing’s syndrome. Most of the patients in the prednisone group had different degrees of Cushing’s syndrome.
Discussion
Hong Kong scholars were the first to apply high-dose dexamethasone to treat patients with newly diagnosed ITP and achieved a response rate of 85%, with half of the effective patients achieving long-term remission with mild adverse effects. Several subsequent studies have reached similar conclusions, and Borst et al. also found that the long-term efficiency rate was significantly higher in primary patients than in relapsed/refractory patients.
The Italian GIMEMA study used a traditional 6-cycle regimen and found that the response rate and long-term efficiency of patients who discontinued treatment after cycles 3-5 were not statistically different from those who completed all 6 cycles, and a subsequent multicenter study shortened each cycle to 14 d and reduced the number of cycles to 4, again confirming that the maximum response rate was achieved after 3 cycles. However, the CR rate increased after the 4th cycle.
A domestic study further shortened the number of cycles to 3 and routinely applied low-dose dexamethasone maintenance therapy and found that the response rate and long-term efficiency were significantly better than those of patients treated with regular doses of prednisone. It should not be overlooked that although response rates were comparable across studies and repeating a certain number of cycles has the potential to improve CR rates and long-term efficiency, evidence from multicenter randomized controlled studies is lacking.
The results of this study showed that the response rate of ITP treated with 2 consecutive courses of high-dose dexamethasone was 83.3% and the long-term effective rate was 68.0%, which is comparable to the findings of the above-mentioned domestic and international studies and superior to conventional prednisone treatment. Most of the patients with effective high-dose dexamethasone treatment responded within 1 week after treatment, suggesting that high-dose dexamethasone treatment has a rapid onset of action compared with prednisone, which can achieve a rapid rise in platelets in a short period of time and thus improve clinical bleeding symptoms more quickly. All patients in the dexamethasone group completed treatment successfully, and most of the adverse reactions were transient and no serious adverse reactions were seen, while most patients in the prednisone group and patients showed different degrees of Cushing’s syndrome.
The mechanism of high-dose dexamethasone in the treatment of ITP is not well understood, and current studies suggest that it may be related to the following factors.
(1) inhibition of dendritic cell maturation and function, thus activating regulatory T cells and suppressing the autoimmune response ;
(2) Correcting the Th1/Th2 imbalance by inhibiting Th1 cytokine secretion while upregulating Th2 cytokine expression;
(3) inhibiting B-cell activating factors, disrupting B-cell maturation and homeostasis, and preventing co-stimulatory signals from activating T cells, and
(4) Inhibit CD8+ T cells, induce apoptosis of bone marrow megakaryocytes, and inhibit platelet production.
Compared with conventional doses of prednisone, high-dose dexamethasone therapy has a rapid onset of action, with efficacy equivalent to that of gammaglobulin at a significantly lower cost, and has a high long-term efficiency, mild adverse effects, and is well tolerated by patients, and is expected to replace prednisone as the first choice for the treatment of ITP, but a multicenter randomized controlled study directly comparing the efficacy of the two has yet to be confirmed. The present single-center randomized study provides support for the aforementioned view.