Methylprednisolone alone or combined with cyclosporine or mycophenolate mofetil for the treatment of immune-mediated hemolytic anemia in dogs, a prospective study

Abstract

Background: Benefit of adding a second-line immunosuppressive drug to glucocorticoids for the treatment of non-associative immune-mediated hemolytic anemia (naIMHA) in dogs has not been defined prospectively.

Hypothesis/objectives: Evaluate the effectiveness of different immunosuppressive protocols in naIMHA dogs.

Animals: Forty-three client-owned dogs.

Methods: Open label, randomized, clinical trial. Dogs were treated with methylprednisolone (M-group), methylprednisolone plus cyclosporine (MC-group) or methylprednisolone plus mycophenolate mofetil (MM-group). Dogs were defined as responders by disappearance of signs of immune-mediated destruction and hematocrit stabilization. Frequency of responders was compared between M-group and combined protocols (MC and MM-group evaluated together), and among the 3 different therapeutic groups at 14 (T14), 30 (T30), 60 (T60) days after admission. Frequency of complications, length of hospitalization and relapse were also compared. Death rate was evaluated at discharge, T60 and 365 (T365) days.

Results: Proportion of responders was not significantly different between M-group and combined protocols (MC and MM-groups), nor among the 3 therapeutic groups at T14, T30, and T60 (P > .17). Frequency of relapse, complications, and length of hospitalization were not significantly different between M-group and dogs treated with combined protocols, nor among the 3 treatment groups (P > .22). Death was significantly more common only for MM-group compared with MC-group at T60 (+42.8%; 95% CI: 11.5-67.4; P = .009), and at T365 (+50%; 95% CI: 17.5-73.2; P = .003).

Conclusions and clinical importance: Combined immunosuppressive therapy did not improve hematological response in naIMHA.

Keywords: IMHA; dog; glucocorticoids; hematological response; immunosuppression; therapy.

FIGURE 1

Flow chart of dogs with immune‐mediated hemolytic anemia (IMHA) included in the study: enrollment, randomization and comparison. aIMHA, associative immune‐mediated hemolytic anemia; naIMHA, non‐associative immune‐mediated hemolytic anemia; M‐group, methylprednisolone therapeutic group; MC‐group, methylprednisolone plus cyclosporine therapeutic group; MM‐group, methylprednisolone plus mycophenolate mofetil therapeutic group. Secondary outcomes: need for packed red blood cells transfusions, duration of hospitalization, number and severity of complications, frequency of relapse and mortality rate. *Assessed in the intention‐to‐treat analysis for primary outcome.

FIGURE 2

Clustered multiple variable graph reporting hematocrit value at different time points for 3 groups of treatment. Blue dots represent methylprednisolone therapeutic group; light blue dots represent methylprednisolone plus cyclosporine therapeutic group; green dots represent methylprednisolone plus mycophenolate mofetil therapeutic group. Central line and whiskers represent the median and the 95% Confidence Interval for median, respectively.

FIGURE 3

Kaplan‐Meier survival curves evaluating survival for dogs with naIMHA divided based on the 3 therapeutic groups. Blue line represents methylprednisolone therapeutic group (M‐group); light blue line represents methylprednisolone plus cyclosporine therapeutic group (MC‐group); green line represents methylprednisolone plus mycophenolate mofetil therapeutic group (MM‐group). A shorter survival was detected for MM‐group if compared with methylprednisolone and MC‐group at T60 (P = .009) and at T365 (P = .003).