Characteristics of included studies [ordered by study ID]
Rao 2006
|
| Methods | Randomised, parallel group trial.
Externally controlled computer randomisation.
Double blind. |
|
| | Participants | 334 leprosy patients with severe type 1 reactions requiring steroid treatment.
Unit of randomisation: person.
Unit of analysis: person.
Persons randomised: 334.
Persons analysed: 269 (a: 88, b: 91, c: 90). |
|
| | Interventions | (a) Prednisolone start at 60 mg/day and thereafter gradually tapered with 10 or 5 mg/2 or 4 weeks until 5 months completed (total 3500 mg).
(a) Prednisolone start at 30 mg/day and thereafter gradually tapered with 5 mg/2, 4 or 8 weeks until 5 months completed (total 2310 mg).
(a) Prednisolone start at 60 mg/day and thereafter gradually tapered with 20 or 10 mg/2 weeks until 3 months completed (total 2940 mg) plus 2 months placebo. |
|
| | Outcomes | (1) Requirement for additional corticosteroids during the 12-month trial period. |
|
| | Notes | Multicentre.
Conducted in six centres in India. |
|
| | Risk of bias |
| | Bias | Authors' judgement | Support for judgement |
| | Random sequence generation (selection bias) | Low risk | Externally controlled computer randomisation. |
| | Allocation concealment (selection bias) | Low risk | Treatments externally assigned. |
| Blinding of participants and personnel (performance bias)
All outcomes | Low risk | The three regimens were presented in blister calendar packs containing the stipulated doses
for 28 days. Each blister pack contained identical looking white tablets whatever the dose of prednisolone or placebo. |
| Blinding of outcome assessment (detection bias)
All outcomes | Low risk | Assessors unaware of treatment assignment. |
| Incomplete outcome data (attrition bias)
All outcomes | Unclear risk | 19.5% loss to follow-up, no differences between the three regimens. Reasons for loss to follow-up not reported. |
| | Selective reporting (reporting bias) | Low risk | Only clinical outcome, no functional outcomes. |
| | Other bias | Low risk | Diagnosis and classification according to internationally accepted criteria of the WHO. No baseline differences between the two groups. |
|
|
Richardus 2003
|
| Methods | Randomised, parallel group trial.
Externally controlled computer randomisation.
Double blind.
Placebo-controlled. |
|
| | Participants | 95 leprosy patients with confirmed MB leprosy diagnosis having untreated sensory or motor impairment of the ulnar or posterior tibial nerve of more than 6 months up to 24 months of duration.
Unit of randomisation: person.
Unit of analysis: ulnar or posterior tibial nerve. Of participants with bilateral NFI, the scores of the least affected limb were used in the analysis. If both limbs were equally affected, then the scores of the right side were used in the analysis.
Persons randomised: 95.
Nerves randomised: 95.
Nerves analysed: 92 (a: 41, b: 51). |
|
| | Interventions | (a) Prednisolone start at 40 mg/day and thereafter gradually tapered with 5 mg/2 weeks until 16 weeks completed (total 2520 mg)
b) Placebo, equivalent number of tablets for 16 weeks |
|
| | Outcomes | Change in:
(1) Sensory score after 1 year, using five graded monofilaments.
(2) Voluntary muscle testing score after 1 year, using modified MRC five-point scale.
(3) Occurrence of major adverse events. |
|
| | Notes | Multicentre.
Conducted in Nepal and Bangladesh.
TRIPOD 3. |
|
| | Risk of bias |
| | Bias | Authors' judgement | Support for judgement |
| | Random sequence generation (selection bias) | Low risk | Externally controlled computer randomisation. |
| | Allocation concealment (selection bias) | Low risk | Treatments externally assigned. |
| Blinding of participants and personnel (performance bias)
All outcomes | Low risk | Treatment regimens similar and the placebo tablets were manufactured to be the same size, shape, and colour as the prednisolone tablets. |
| Blinding of outcome assessment (detection bias)
All outcomes | Low risk | Assessors unaware of treatment assignment. |
| Incomplete outcome data (attrition bias)
All outcomes | Low risk | Only 3% loss to follow-up. |
| | Selective reporting (reporting bias) | Low risk | Primary outcomes, sensory and motor NFI after 1 year, have been measured and reported. |
| | Other bias | Low risk | Diagnosis and classification according to internationally accepted criteria of the WHO. No baseline differences between the two groups. |
|
|
Van Brakel 2003
|
| Methods | Randomised, parallel group trial.
Externally controlled computer randomisation.
Double blind.
Placebo-controlled. |
|
| | Participants | 84 leprosy patients with confirmed MB leprosy diagnosis having sensory impairment of the ulnar or posterior tibial nerve of less than 6-months duration, as measured with the Semmes-Weinstein test. The ballpen test had to be normal.
Unit of randomisation: person.
Unit of analysis: ulnar or posterior tibial nerve. Of participants with bilateral nerve function impairment, the scores of the most affected limb were used in the analysis. If both limbs were equally affected, then the scores of the right side were used in the analysis.
Persons randomised: 84.
Nerves randomised: 84.
Nerves analysed: 75 (a: 41, b: 34). |
|
| | Interventions | (a) Prednisolone start at 40 mg/day and thereafter gradually tapered with 5 mg/2 weeks until 16 weeks completed (total 2520 mg).
(b) Placebo, equivalent number of tablets for 16 weeks. |
|
| | Outcomes | Change in:
(1) Sensory score after 1 year, using five graded monofilaments.
(2) Occurrence of major adverse events. |
|
| | Notes | Multicentre.
Conducted in Nepal and Bangladesh.
TRIPOD 2. |
|
| | Risk of bias |
| | Bias | Authors' judgement | Support for judgement |
| | Random sequence generation (selection bias) | Low risk | Externally controlled computer randomisation. |
| | Allocation concealment (selection bias) | Low risk | Treatments externally assigned. |
| Blinding of participants and personnel (performance bias)
All outcomes | Low risk | Treatment regimens were similar and the placebo tablets were manufactured to be the same size, shape, and colour as the prednisolone tablets. |
| Blinding of outcome assessment (detection bias)
All outcomes | Low risk | Assessors unaware of treatment assignment. |
| Incomplete outcome data (attrition bias)
All outcomes | Unclear risk | 11% loss to follow-up. Reasons for loss to follow-up not reported. |
| | Selective reporting (reporting bias) | Low risk | Primary outcome, sensory NFI after 1 year, has been measured and reported. |
| | Other bias | Low risk | Diagnosis and classification according to internationally accepted criteria of the WHO. No baseline differences between the two groups. |
|
|
Abbreviations: MB: multibacillary; WHO: World Health Organization; NFI: nerve function impairment.
Characteristics of excluded studies [ordered by study ID]
|
| Study | Reason for exclusion |
|---|
| | Boucher 1999 | Comparing surgical decompression in addition to corticosteroids versus corticosteroids. |
| | Croft 2000 | Case-control study. No randomisation procedure. |
| | Dandapat 1991 | Unclear randomisation procedure. |
| | Ebenezer 1996 | Comparing surgical decompression in addition to corticosteroids versus corticosteroids. |
| | Garbino 2007 | Outcomes six months after treatment, no separate results for type 1 reactions. |
| | Jardim 2007 | Steroid prophylaxis for prevention of nerve function impairment in leprosy. No randomisation procedure. |
| | Marlowe 2004 | Comparing azathioprine in combination with corticosteroids versus corticosteroids. |
| | Marlowe 2007 | Open trial. No randomisation procedure. |
| | Pannikar 1984 | Comparing surgical decompression in addition to corticosteroids versus corticosteroids. |
| | Smith 2004 | Steroid prophylaxis for prevention of nerve function impairment in leprosy. |
| | Wilder-Smith 1997 | Case-control study. No randomisation procedure. |
|
|
Comparison 1. Corticosteroids versus placebo
|
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|
| | 1 Change in sensory score after one year | 2 | | Mean Difference (IV, Fixed, 95% CI) | Subtotals only |
| | | 1 | 75 | Mean Difference (IV, Fixed, 95% CI) | 0.32 [-0.91, 1.55] |
| | | 1 | 89 | Mean Difference (IV, Fixed, 95% CI) | 0.42 [-0.57, 1.41] |
| | 2 Proportion with sensory improvement after one year | 2 | | Risk Ratio (M-H, Fixed, 95% CI) | Subtotals only |
| | | 1 | 75 | Risk Ratio (M-H, Fixed, 95% CI) | 1.01 [0.81, 1.27] |
| | | 1 | 71 | Risk Ratio (M-H, Fixed, 95% CI) | 0.97 [0.65, 1.45] |
| | 3 Change in motor score after one year | 1 | | Mean Difference (IV, Fixed, 95% CI) | Subtotals only |
| | | 1 | 21 | Mean Difference (IV, Fixed, 95% CI) | 0.12 [-0.76, 1.00] |
| | 4 Proportion with motor improvement after one year | 1 | | Risk Ratio (M-H, Fixed, 95% CI) | Subtotals only |
| | | 1 | 3 | Risk Ratio (M-H, Fixed, 95% CI) | 4.5 [0.32, 63.94] |
| | 5 Proportion with serious adverse events | 2 | 167 | Risk Ratio (M-H, Fixed, 95% CI) | 1.47 [0.35, 6.24] |
| | | 1 | 75 | Risk Ratio (M-H, Fixed, 95% CI) | 0.83 [0.05, 12.77] |
| | | 1 | 92 | Risk Ratio (M-H, Fixed, 95% CI) | 1.87 [0.33, 10.64] |
|
|
Comparison 2. High dose versus low dose five-month course corticosteroids
Comparison 3. High dose five-month versus three-month course corticosteroids
Comparison 4. Low dose versus short course corticosteroids
Table 1. Leprosy classification - Ridley Jopling WHO 1998
|
| Ridley-Jopling | WHO |
| | TT: tuberculoid leprosy | PB: paucibacillary leprosy |
| | BT: borderline tuberculoid leprosy | PB |
| | BB: borderline leprosy | MB: multibacillary leprosy |
| | BL: borderline lepromatous leprosy | MB |
| | LL: lepromatous leprosy | MB |
|
|
Table 2. Sensory scoring system - Van Brakel et al.
|
| Colour | Approximate force | Score for hand | Score for foot |
| | blue filament felt | 200 mg | 0 | |
| | purple filament felt | 2 g | 1 | 0 |
| | red filament felt | 4 g | 2 | 1 |
| | orange filament felt | 10 g | 3 | 2 |
| | pink filament felt | 300 g | 4 | 3 |
| | pink filament not felt | | 5 | 4 |
|
|
Table 3. Modified MRC scale - Brandsma 1981
|
| Grade | Definition |
| | 5 | Full range of movement of the joint on which the muscle or muscle group is acting. Normal resistance can be given. |
| | 4 | Full range of movement but less than normal resistance. |
| | 3 | Full range of movement but no resistance. |
| | 2 | Partial range of movement with no resistance. |
| | 1 | Perceptible contraction of the muscle(s) not resulting in joint movement. |
| | 0 | Complete paralysis. |
|
|
Table 4. Scoring system for nerve pain and tenderness - Pearson
|
| Score | Grade |
| | Nerve pain | |
| | 3 | absent |
| | 2 | mild (only aware intermittently and does not limit activity) |
| | 1 | moderate (sleep disturbed, activities diminished, work efficiency diminished) |
| | 0 | severe (incapacitating) |
| | Nerve tenderness | |
| | 3 | absent |
| | 2 | mild (absent if patients' attention is distracted) |
| | 1 | moderate (present if attention is distracted) |
| | 0 | severe (very tender and patient withdraws the arm forcibly) |
|
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