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Table 3 Summary of eligible studies reporting outcomes from treatment with immunomodulatory and immunosuppressive drug protocols in canine primary ITP

From: Immunomodulatory and immunosuppressive drug protocols in the treatment of canine primary immune thrombocytopenia, a scoping review

Study

Level of evidence, study design, and methodological quality

Study population (range)

Intervention and comparator

Outcome and adverse events (range)

Statistical comparison (P value or [95% Cl])

Kohn et al. [7]

LOE 3

Prospective case series

Very small number of dogs in each group

Uncertain enrollment

15 client-owned dogs with a diagnosis of ITP with a mean initial platelet count of 10,400/µL (0–74,000/µL)

13 dogs reached the outcome

Treatment during beginning of disease:

Tx1: Prednisolone 1–1.5 mg/kg BID

Tx2: Prednisolone 1–1.5 mg/kg BID + Aza 1,5-2 mg/kg SID

Tx3; Prednisolone 1–1.5 mg/kg BID + Aza 1.5-2 mg/kg SID (4–7 days after Vinc Inj) + Vinc 0.5 mg/m2 once or possibly after 1 week

Platelet recovery > 50.000/µL:

Tx1: 1, 2, 3, 3, 4, 5 and 9 days

Tx2: 3, 3 and 11 days

Tx3: 2, 3 and 5 days

Platelet recovery > 150,000/µL:

Tx1: 3, 5, 6, 6, 6, 11 and 13 days

Tx2: 6, 10 and 22 days

Tx3: 4, 5 and 13 days

Adverse events:

Tx2 and Tx3: Grade 5 death

No statistical evaluation of outcome

Balog et al. [14]

LOE 1+ (Randomized), multicenter, blinded, clinical trial

Small number of dogs in each group

Uncertain enrollment

20 client-owned dogs with a diagnosis of severe primary ITPwith a median initial platelet count of 1000/µL (0–16,000/µL)

Treatment within 24 h of initial presentation to day 7:

Tx1: Prednisone 1.5-2 mg/kg BID or Dex 0.2–0.3 mg/kg SID + hIVIG 0.5 g/kg once

C: Prednisone 1.5-2 mg/kg BID or Dex 0.2–0.3 mg/kg SID + Vinc 0.02 mg/kg once

Adjunctive treatment after day 7 if no platelet recovery occurred:

Alternative drug (VINC or hIVIG) + Aza 2 mg/kg SID

Platelet recovery ≥ 40,000/µL:

Tx1: median 2.5 days (0–10 days)

C: median 2.5 days (1–4 days)

Duration of hospitalizationa:

Tx1: median 5 days (1.5–10 days)

C: median 4 days (3–5 days)

Survival to discharge:

Tx1: 70%

C: 100%

Survival 6-month:

Tx1: 22%

C: 70%

Survival 1-year:

Tx1: 22%

C: 60%

Adverse events:

Tx1 and C: Grade 1 mild

No significant difference (P < 0.05) in platelet recovery time (P = 0.51), duration of hospitalization (P = 0.29), survival to discharge (P = .21), survival 6-months (P = 0.17) and survival 1-year (P = 0.07) between groups

Bianco et al. [26]

LOE 1++

Randomized, double-blinded, placebo-controlled, clinical trial

Very small number of dogs in each group

Strongly supportive enrollment

18 client-owned dogs with a presumptive diagnosis of primary ITP with a median initial platelet count of 2000/µL (1000–18,000/µL)

Treatment within 24 h of initial presentation to day 7:

Tx1: Prednisone 1.5 mg/kg BID + hIVIG 0.5 g/kg once

C: Prednisone 1.5 mg/kg BID + Placebo (0.9% NaCl)

Adjunctive treatment on day 7 if no platelet recovery occurred or to decrease dosage of prednisone:

Alternative drug (Placebo or hIVIG) + Aza 2 mg/kg SID, Vinc 0.02 mg/kg once and Cyclo 5 mg/kg BID in different combinations

Platelet recovery > 40,000/µL:

Tx1: median 3,5 days (2–7 days) mean 3.7 ± 1.3 days SD

C: median 7.5 days (3–12) mean 7.8 ± 3.9 days SD

Duration of hospitalizationb:

Tx1: median 4 days (2–8) mean 4.2 ± 0.4 days SD

C: median 8 days (4–12) mean 8.3 ± 0.6 days SD

Platelet recovery > 160,000/µL:

Tx1: median 8 days (3–19)

C: median 13 days (5–32)

Survival to discharge:

Tx1: 100%

C: not described

Survival 6-month:

Tx1:100%

C:78%

Relapse during 6-monthc:

Tx1: 11%

C: 11%

Adverse events:

Tx1: Grade 1 mild

C: Grade 1 mild

Significant difference (P < 0.05) in platelet recovery time > 40,000/µl (P = 0.018) and duration of hospitalization (P = 0.027) between groups

No significant difference in platelet recovery > 160,000/µl (P = 0.093) or survival 6-months (P = 0.79) between the two initial groups and between all dogs that did not receive hIVIG and those that did at some point during the 6-month period (P = 0.53)

Putsche and Kohn [5]

LOE 3

Retrospective case series with a nested cohort study

Small to very small number of dogs in each group

Uncertain enrollment

30 client-owned dogs with a diagnosis of primary ITP with a median initial platelet count of 8000/µL (0–111,000/µL)

Treatment during disease:

Tx1: Prednisolone 1–1.5 mg/kg BID

Tx2: Prednisolone 1–1.5 mg/kg BID + Vinc 0.02 mg/kg (Fq not described)

Tx3: Prednisolone 1–1.5 mg/kg BID + Aza 1.5-2 mg/kg SID

Tx4: Prednisolone 1–1.5 mg/kg BID + Cyclo 5 mg/kg SID

C: Tx2 + Tx3 + Tx4

Adjunctive treatment at beginning of treatment or 5–43 days later, if no platelet recovery occurred or after a relapse

Platelet recovery ≥ 50,000/µL:

Tx1: median 5 days (4–11 days) mean 6 ± 2.2 days SD

Tx2: median 4 days (2–7 days) mean 4 ± 2 days SD

Tx3: 4, 7 and 12 days

Tx4: 5 and 9 days

Adverse events:

Tx3: Grade 5 death

No significant difference (P < 0.05) in relapse (P = 0.676) and mortality (P = 0.367) between Tx1 and C during 1684 days. Relapse: 26% [9%–51%] and Mortality: 10% [2%–27%]

Huang et al. [27]

LOE 3

Retrospective (case- control study)

Small to very small number of dogs in each group

Uncertain enrollment

48 client-owned dogs with a diagnosis of presumptive primary ITP, some had recent vaccination, with a median initial platelet count of 1000/µL (0–39,500/µL)

Treatment during hospitalization:

Tx1: Prednisone 1-4 mg/kg/day or Dex 0.04–0.5 mg/kg/day + Aza 2 mg/kg/day

Tx2: Prednisone 1-4 mg/kg/day or Dex 0.04–0.5 mg/kg/day + Vinc 0.02 mg/kg once

Tx3: Prednisone 1-4 mg/kg/day or Dex 0.04–0.5 mg/kg/day + hIVIG 0.35–0.81 g/kg once

Platelet recovery = 40,000/µL:

Tx1: median 6 days (4–12)

Tx2: median 4 days (2–10)

Tx3: median 5 days (2–10)

Platelet recovery to reach reference range:

Tx1: median 15 days (12–21)

Tx2: median 10 days (3–42)

Tx3: median 12 days (2–13)

Survival to discharge:

Tx1: 70%

Tx2: 90%

Tx3: 83%

No evaluation of adverse events

No statistical evaluation of outcome

Yau and Bianco [13]

LOE 3

Prospective case series

Very small number of dogs in each group

Uncertain enrollment

5 client-owned dogs with a diagnosis of presumptive ITP, chronically treated NSAIDs for osteoarthritis with a median initial platelet count of 3000/µL (1000–14,000/µL)

Treatment during beginning of disease:

Tx1: Mycophenolate mofetil 7.1–14.4 mg/kg BID, median 8.5 mg/kg

Platelet recovery > 50,000/µL:

Tx1: median 3 days (2–6 days)

Duration of hospitalization:

Tx1: median 3 days (2-7 days)

Platelet recovery ≥ 170,000/µL:

Tx1: median 9 days (5–16 days)

Survival to discharge:

Tx1: 100%

Adverse events:

Tx1: Grade 2 moderate

No statistical evaluation of outcome

  1. Aza, azathioprine; BID, twice a day; C, comparator; (case–control study), investigating association between recent vaccination and ITP but case series for the therapeutic intervention; Cl, confidence interval [lower limit, upper limit]; Cyclo, cyclosporine; Dex, dexamethasone; Fq, frequency; hIVIG, human intravenous immunoglobulin; NSAIDs, non-steroidal anti-inflammatory drugs; Inj, injection; (randomized), study claimed to be randomized but procedure not described; LOE, level of evidence; SD, standard deviation; SID, once a day; Tx1-4, Immunomodulatory and/or immunosuppressive treatment; Vinc, Vincristine
  2. aDefined: initial presentation to discharge when platelet counts ≥ 40,000/µL
  3. bDefined: initial presentation to discharge when clinical stable and platelet counts > 40,000/µL
  4. cDefined: a platelet count decrease of 50% compared to previous count or any count of < 40,000/µL after initial response