Randomised Controlled Trial of High Dose Dexamethasone and Methylprednisolone in Immune Thrombocytopenia (HDMI Trial)

Background: Immune Thrombocytopenia (ITP) is an autoimmune disorder characterized by a platelet count less than 100x10⁹/L. The treatment is required mostly when the platelet count falls below 30x10⁹/L. The first line of therapy is corticosteroids, which take 2-7 days to achieve the maximum effect on the platelet count. There has been a debate on whether a particular corticosteroid can produce a better response in ITP. Multiple research data have supported the use of dexamethasone for both early and persistent response in ITP. However, there are not many randomized controlled trials to prove it. Hence, most guidelines recommend corticosteroids as the first-line therapy but don’t recommend any specific corticosteroids for use in ITP. Most of the research works, which recommended dexamethasone for better treatment response in ITP, compared dexamethasone with prednisolone. Hence, there is a scope for further research to investigate the other corticosteroids in the management of ITP. Therefore, we aimed to compare the dexamethasone with methylprednisolone pulse followed by prednisolone continuation.

Design and methods: This study was conducted from August 2021 to Feb 2023 at a tertiary care center in northern India. ITP patients of any gender and age 18 years or more requiring corticosteroids were screened for inclusion in the study. Patients having secondary ITP, chronic disorders affecting platelets (chronic liver disease, hypersplenism, connective tissue disorders), and patients who could not be followed up for at least six months after the beginning of the study were excluded from the study. Group-1 (intervention arm) patients received intravenous methylprednisolone (MP) (1g MP iv infusion over 2-3 hours for three days) followed by oral prednisolone at a dose of 1 mg/kg/day once daily (maximum up to six weeks). Group 2 patients received oral dexamethasone (Dexa) at a fixed dose of 40 mg/day once daily for four days (maximum up to three cycles at a gap of 14 days).

Results: A total of 127 patients with ITP were randomized in two arms [63 in Group-1 (MP) and 64 in Group-2 (Dexa)] of the study. The median age was 34 years and 33% were males. After one week of therapy, there was a rapid and statistically significant increase in mean platelets for both arms. MP raised the platelets to almost one lac within one week, however, with time there was a drop in mean platelets to around 70x10⁹/L. On the other hand, the initial peak for Dexa was only about 60x10⁹/L within the first week, which was followed by a drop in platelet count till day 15, after which there was an increase in platelet count to around 70x10⁹/L, and it stayed like that till the end of the study. On day eight, the overall response was 55% and 50.2% and the complete response rate was 24.2% and 20% in MP and dexa arms respectively. The day seven platelets were a strong determinant for the later kinetics of platelets. So, a separate analysis was done to assess the difference in early platelet response (D7 platelets) and late platelet kinetics (post D7 platelets) between the dexamethasone and methylprednisolone groups. After six weeks, both MP and Dexa were almost equal in efficacy. MP, which had a much better early response than Dexa, after 6th week had a significant drop in platelets, unlike dexa, which had a continued rise in platelets or static platelets. At the end of six weeks of follow-up, both dexa and MP were equal in efficacy. At day 43, the overall response was 63% and 60.6% in MP and dexa arms respectively. The complete response was 29.4% and 26.6% respectively.

Adverse events occurred in equal proportion in both the arms (methylprednisolone 28.6% (18/63), and dexamethasone 31.2% (20/64). As there were no grade three or more adverse events, they were easily managed without discontinuing the treatment. The commonest adverse event was weight gain seen in 16.5% (21/127) of the patients.

Conclusion: Though dexamethasone and methylprednisolone showed comparable long-term efficacy and adverse events, considering a statistically significant better early platelet response with methylprednisolone, we concluded that methylprednisolone is better than dexamethasone in treating ITP.