Corticosteroids for treating nerve damage in leprosy

Natasja HJ Van Veen; Peter G Nicholls; W Cairns S Smith; Jan Hendrik Richardus

doi:10.1002/14651858.CD005491.pub3

Corticosteroides para el tratamiento del daño nervioso en la lepra

Appendices

Appendix 1. Cochrane Neuromuscular Specialised Register (CRS) search strategy

#1 MeSH DESCRIPTOR Leprosy Explode All [REFERENCE] [STANDARD]
#2 hansen*:ti or hansen:ab [REFERENCE] [STANDARD]
#3 lepr*:ti or lepr*:ab [REFERENCE] [STANDARD]
#4 #1 or #2 or #3 [REFERENCE] [STANDARD]
#5 MeSH DESCRIPTOR Adrenal Cortex Hormones Explode All [REFERENCE] [STANDARD]
#6 prednisone* or prednisolone* or cortisone* or cyclosporine* or azathioprine* [REFERENCE] [STANDARD]
#7 methylprednisolone or glucocorticoid* or corticosteroid* or "cortical hormone" or "cortical hormones" [REFERENCE] [STANDARD]
#8 #5 or #6 or #7 [REFERENCE] [STANDARD]
#9 MeSH DESCRIPTOR Peripheral Nervous System Diseases Explode All [REFERENCE] [STANDARD]
#10 neuritis or neuropath* or "nerve damage" or "nerve involvement" [REFERENCE] [STANDARD]
#11 "nerve loss" or "nerve function impairment" or "nerve problem" or "nerve problems" [REFERENCE] [STANDARD]
#12 "sensory loss" or "motor loss" or "motor function loss" [REFERENCE] [STANDARD]
#13 "nerve pain" or "nerve tenderness" [REFERENCE] [STANDARD]
#14 reaction* [REFERENCE] [STANDARD]
#15 #9 or #10 or #11 or #12 or #13 or #14 [REFERENCE] [STANDARD]
#16 #4 and #8 and #15 [REFERENCE] [STANDARD]
#17 (#4 and #8 and #15) AND (INREGISTER) [REFERENCE] [STANDARD]

Appendix 2. CENTRAL search strategy

#1 leprosy
#2 MeSH descriptor Leprosy explode all trees
#3 "hansen disease"
#4 (#1 OR #2 OR #3)
#5 "peripheral nervous system diseases" or "peripheral nerves"
#6 MeSH descriptor Peripheral Nervous System Diseases explode all trees
#7 (neuritis or neuralgia or neuropath* or "nerve damage" or "nerve involvement" or "nerve loss" or "nerve function impairment" or "nerve problem" or "sensory loss" or "motor loss" or "motor function loss" or "nerve pain" or "nerve tenderness" or reaction$)
#8 (#5 OR #6 OR #7)
#9 MeSH descriptor Adrenal Cortex Hormones explode all trees
#10 (prednisolone or prednisone or cortisone or cyclosporin or ciclosporin or azathioprine or methylprednisolone or betamethasone)
#11 (glucocorticoid* or corticosteroid* or prednisolon* or prednison* or cortison* or "cortical hormones" or "cortical hormone" or cyclosporin* or ciclosporin* or azathioprin* or methylprednisolon* or betamethason*)
#12 (#9 OR #10 OR #11)
#13 (#4 AND #8 AND #12)

Appendix 3. MEDLINE (OvidSP) search strategy

Database: Ovid MEDLINE(R) <1946 to June Week 1 2015>
Search Strategy:
‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐
1 randomized controlled trial.pt. (396862)
2 controlled clinical trial.pt. (89648)
3 randomized.ab. (293733)
4 placebo.ab. (152857)
5 drug therapy.fs. (1782093)
6 randomly.ab. (207091)
7 trial.ab. (303153)
8 groups.ab. (1318490)
9 or/1‐8 (3363492)
10 exp animals/ not humans.sh. (4057817)
11 9 not 10 (2863375)
12 exp Leprosy/ (20239)
13 hansen* disease.tw. (829)
14 12 or 13 (20301)
15 exp Adrenal Cortex Hormones/ (344770)
16 Prednisolone/ (29599)
17 Prednisone/ (35381)
18 Cortisone/ (15363)
19 Cyclosporine/ (26754)
20 Azathioprine/ (13448)
21 Methylprednisolone/ (16493)
22 Betamethasone/ (5331)
23 (glucocorticoid$ or corticosteroid$ or prednisolon$ or prednison$ or cortison$ or cortical hormones$ or cyclosporin$ or ciclosporin$ or azathioprin$ or methylprednisolon$ or betamethason$).tw. (216209)
24 or/15‐23 (451754)
25 11 and 14 and 24 (385)
26 exp Peripheral Nervous System Diseases/ (119912)
27 (neuritis or neuropath$ or nerve damage or nerve involvement or nerve loss or nerve function impairment or nerve problem or sensory loss or motor loss or motor function loss or nerve pain or nerve tenderness or reaction$ or reversal reaction$ or type 1 reaction or type 2 reaction).tw. (885639)
28 26 or 27 (969292)
29 11 and 14 and 24 and 28 (260)
30 remove duplicates from 29 (259)

Appendix 4. EMBASE (OvidSP) search strategy

Database: Embase <1980 to 2015 Week 24>
Search Strategy:
‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐
1 crossover‐procedure/ (43171)
2 double‐blind procedure/ (121038)
3 randomized controlled trial/ (373903)
4 single‐blind procedure/ (20388)
5 (random$ or factorial$ or crossover$ or cross over$ or cross‐over$ or placebo$ or (doubl$ adj blind$) or (singl$ adj blind$) or assign$ or allocat$ or volunteer$).tw. (1464106)
6 clinical trial/ (845836)
7 or/1‐6 (2014785)
8 exp animals/ (19964586)
9 exp humans/ (15918733)
10 8 not (8 and 9) (4045853)
11 7 not 10 (1855155)
12 limit 11 to embase (1511872)
13 exp LEPROSY/ (23445)
14 hansen$ disease.tw. (1180)
15 leprosy.tw. (18747)
16 or/13‐15 (25694)
17 exp Peripheral Neuropathy/ (53096)
18 neuritis.mp. (16732)
19 neuropath$.mp. (224458)
20 nerve damage.mp. (5418)
21 nerve involvement.mp. (2736)
22 nerve loss.mp. (125)
23 nerve function impairment.mp. (110)
24 nerve problem$.mp. (142)
25 sensory loss.mp. (3119)
26 motor loss.mp. (240)
27 motor function loss.mp. (43)
28 nerve pain.mp. (268)
29 nerve tenderness.mp. (18)
30 reaction$.tw. (1029628)
31 reversal reaction.mp. (604)
32 type 1 reaction$.mp. (225)
33 type 2 reaction$.mp. (135)
34 erythema nodosum leprosum.mp. (1241)
35 or/17‐34 (1267303)
36 (steroid$ or glucocorticoid$ or corticosteroid$ or prednisolon$ or prednison$ or cortical hormone$ or cyclosporin A or azathioprin$ or methylprednisolon$ or betamethason$ or cortison$).mp. (840421)
37 exp decompression surgery/ (36094)
38 (necrolysis or epicondylectomy).mp. (6971)
39 or/36‐38 (878190)
40 exp peripheral neuropathy/ (53096)
41 (neuritis or neuropath$ or nerve damage or nerve involvement or nerve loss or nerve function impairment or nerve problem$).mp. (241878)
42 (sensory loss or motor loss or motor function loss or nerve pain or nerve tenderness or reaction$ or reversal reaction or type 1 reaction$ or type 2 reaction$ or erythema nodosum leprosum).mp. (1868057)
43 12 and 16 and 39 and 42 (119)

Appendix 5. LILACS (BIREME IAHx) search strategy

(MH:C01.252.410.040.552.386$ or leprosy or lepra or hanseniase) and (prednisone or prednisona or prednisolone or prednisolona or cortisone or cortisona or cyclosporine or ciclosporina or azathioprine or azatioprina or methylprednisolone or metilprednisolona or betamethasone or betametasona or glucocorticoid$ or corticosteroid$ or corticoesteroid$) and ((PT:"Randomized Controlled Trial" or "Randomized Controlled trial" or "Ensayo Clínico Controlado Aleatorio" or "Ensaio Clínico Controlado Aleatório" or PT:"Controlled Clinical Trial" or "Ensayo Clínico Controlado" or "Ensaio Clínico Controlado" or "Random allocation" or "Distribución Aleatoria" or "Distribuição Aleatória" or randon$ or Randomized or randomly or "double blind" or "duplo‐cego" or "duplo‐cego" or "single blind" or "simples‐cego" or "simples cego" or placebo$ or trial or groups) AND NOT (B01.050$ AND NOT (humans or humanos or humanos)))

Appendix 6. CINAHL (EBSCOhost) search strategy

Tuesday, June 16, 2015 11:00:19 AM

S34 S15 and S33 7
S33 S16 or S17 or S18 or S19 or S20 or S21 or S22 or S23 or S24 or S25 or S26 or S27 or S28 or S29 or S30 or S31 or S32 752,583
S32 ABAB design* 93
S31 TI random* or AB random* 151,010
S30 ( TI (cross?over or placebo* or control* or factorial or sham? or dummy) ) or ( AB (cross?over or placebo* or control* or factorial or sham? or dummy) ) 301,434
S29 ( TI (clin* or intervention* or compar* or experiment* or preventive or therapeutic) or AB (clin* or intervention* or compar* or experiment* or preventive or therapeutic) ) and ( TI (trial*) or AB (trial*) ) 105,987
S28 ( TI (meta?analys* or systematic review*) ) or ( AB (meta?analys* or systematic review*) ) 36,870
S27 ( TI (single* or doubl* or tripl* or trebl*) or AB (single* or doubl* or tripl* or trebl*) ) and ( TI (blind* or mask*) or AB (blind* or mask*) ) 23,445
S26 PT ("clinical trial" or "systematic review") 127,929
S25 (MH "Factorial Design") 945
S24 (MH "Concurrent Prospective Studies") or (MH "Prospective Studies") 264,883
S23 (MH "Meta Analysis") 22,461
S22 (MH "Solomon Four‐Group Design") or (MH "Static Group Comparison") 48
S21 (MH "Quasi‐Experimental Studies") 7,381
S20 (MH "Placebos") 9,272
S19 (MH "Double‐Blind Studies") or (MH "Triple‐Blind Studies") 31,799
S18 (MH "Clinical Trials+") 188,614
S17 (MH "Crossover Design") 13,034
S16 (MH "Random Assignment") or (MH "Random Sample") or (MH "Simple Random Sample") or (MH "Stratified Random Sample") or (MH "Systematic Random Sample") 69,594
S15 S3 and S14 28
S14 S4 or S5 or S6 or S7 or S8 or S9 or S10 or S11 or S12 or S13 32,265
S13 (cortison*) or (MH "Cortisone") 389
S12 (betamethason*) or (MH "Betamethasone") 540
S11 (methylprednisolon*) or (MH "Methylprednisolone") 2,083
S10 (azathioprin*) or (MH "Azathioprine") 1,245
S9 (cyclosporin A) or (MH "Cyclosporine") 1,689
S8 prednison* 3,674
S7 (prednisolon*) or (MH "Prednisolone") 2,393
S6 corticosteroid* 9,046
S5 (glucocorticoid*) or (MH "Glucocorticoids") 6,518
S4 (steroid) or (MH "Steroids") 11,910
S3 S1 or S2 1,210
S2 hansen disease 11
S1 (leprosy) or (MH "Leprosy") 1,210

Figure 1

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.1

Comparison 1 Corticosteroids versus placebo, Outcome 1 Improvement in sensory score after one year.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.2

Comparison 1 Corticosteroids versus placebo, Outcome 2 Proportion with sensory improvement after one year.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.3

Comparison 1 Corticosteroids versus placebo, Outcome 3 Proportion with serious adverse events.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.4

Comparison 1 Corticosteroids versus placebo, Outcome 4 Improvement in motor score after one year.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.5

Comparison 1 Corticosteroids versus placebo, Outcome 5 Proportion with motor improvement after one year.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.1

Comparison 2 High‐dose versus low‐dose five‐month course corticosteroids, Outcome 1 Proportion needing additional corticosteroids during 12 months.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 3.1

Comparison 3 High‐dose five‐month versus three‐month course corticosteroids, Outcome 1 Proportion needing additional corticosteroids during 12 months.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 4.1

Comparison 4 Low‐dose versus short‐course corticosteroids, Outcome 1 Proportion needing additional corticosteroids during 12 months.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 5.1

Comparison 5 Intravenous methylprednisolone and oral prednisolone versus intravenous normal saline and oral prednisolone, Outcome 1 Adverse events.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Summary of findings for the main comparison. Corticosteroids compared with placebo for treating nerve damage (< 6 months' duration) in leprosy

Corticosteroids compared with placebo for treating nerve damage (< 6 months' duration) in leprosy
Patient or population: people with nerve damage (< 6 months' duration) in leprosy Settings: Nepal and Bangladesh Intervention: corticosteroids (prednisolone started at 40 mg/day then gradually tapered) Comparison: placebo
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	Number of participants (studies)	Quality of the evidence (GRADE)	Comments
	Risk with placebo	Risk with corticosteroids
Improvement in sensory nerve function at 1 year Defined as a reduction in sensory score by 3 or more points from baseline	Study population		RR 1.01 (0.81 to 1.27)	75 nerves (1 RCT)	⊕⊕⊕⊝ moderate¹	‐
	794 per 1000	802 per 1000 (643 to 1000)
Improvement in motor nerve function at 1 year ‐ not reported	‐	‐	‐	‐	‐	‐
Change in nerve pain and in nerve tenderness at 1 year ‐ not reported	‐	‐	‐	‐	‐	‐
Limitations in activities of daily living at 1 year ‐ not reported	‐	‐	‐	‐	‐	‐
Limitations in participation at 1 year ‐ not reported	‐	‐	‐	‐	‐	‐
Adverse events Assessed as: occurrence of one or more major adverse events requiring withdrawal of treatment	Study population		RR 0.83 (0.05 to 12.77)	75 nerves (1 RCT)	⊕⊕⊕⊝ moderate¹	‐
	29 per 1000	24 per 1000 (1 to 376)
*The risk in the intervention group (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; RCT: randomised controlled trial; RR: risk ratio
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
¹Small sample size.

Summary of findings for the main comparison. Corticosteroids compared with placebo for treating nerve damage (< 6 months' duration) in leprosy

Corticosteroids compared to placebo for treating nerve damage (6 to 24 months' duration) in leprosy
Patient or population: people with nerve damage (6 to 24 months' duration) in leprosy Setting: Nepal and Bangladesh Intervention: corticosteroids (prednisolone starting at 40 mg/day and gradually tapered) Comparison: placebo
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	Number of participants (studies)	Quality of the evidence (GRADE)	Comments
	Risk with placebo	Risk with corticosteroids
Improvement in sensory nerve function at 1 year Assessed with: graded nylon filaments Defined as a reduction by 3 or more points from baseline	Study population		RR 0.97 (0.65 to 1.45)	71 (1 RCT)	⊕⊕⊕⊝ moderate¹	‐
	585 per 1000	568 per 1000 (380 to 849)
Improvement in motor nerve function at 1 year Assessed with: MRC scale, inverted for the purposes of the trial (a more negative change score indicated an improvement)	The mean improvement in motor nerve function at 1 year was ‐0.30 ± 1.6 points	The mean improvement in motor nerve function at 1 year in the intervention group was 0.12 points higher (0.76 lower to 1.00 higher)	‐	21 (1 RCT)	⊕⊕⊝⊝ low²	The MD slightly favoured the placebo group, but not significantly (MD 0.12, 95% CI ‐0.76 to 1.00)
Change in nerve pain and in nerve tenderness at 1 year ‐ not reported	‐	‐	‐	‐	‐	‐
Limitations in activities of daily living at 1 year ‐ not reported	‐	‐	‐	‐	‐	‐
Limitations in participation at 1 year ‐ not reported	‐	‐	‐	‐	‐	‐
Adverse events Assessed as adverse events requiring withdrawal of treatment	Study population		RR 1.87 (0.33 to 10.64)	92 (1 RCT)	⊕⊕⊕⊝ moderate¹	‐
	39 per 1000	73 per 1000 (13 to 417)
*The risk in the intervention group (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; MD: mean difference; MRC: Medical Research Council; RCT: randomised controlled trial; RR: risk ratio
GRADE Working Group grades of evidence High quality: We are very confident that the true effect lies close to that of the estimate of the effect Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect
¹Small sample size. ²Very small sample size: 21 participants with motor nerve function impairment.

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

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

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
MRC: Medical Research Council

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 person's attention is distracted)
1	Moderate (present if attention is distracted)
0	Severe (very tender and person withdraws the arm forcibly)

High‐dose corticosteroids compared to low‐dose corticosteroids for treating nerve damage in leprosy (5‐month regimens)
Patient or population: people with nerve damage in leprosy (severe type 1 leprosy reaction) Setting: India Intervention: high‐dose corticosteroids (60 mg/day before tapering) Comparison: low‐dose corticosteroids (30 mg/day before tapering)
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	Number of participants (studies)	Quality of the evidence (GRADE)	Comments
Outcomes	Risk with low‐dose corticosteroids	Risk with high‐dose corticosteroids	Relative effect (95% CI)	Number of participants (studies)	Quality of the evidence (GRADE)	Comments
Improvement in sensory nerve function at 1 year ‐ not reported	‐	‐	‐	‐	‐	‐
Improvement in motor nerve function at 1 year ‐ not reported	‐	‐	‐	‐	‐	‐
Change in nerve pain and in nerve tenderness at 1 year ‐ not reported	‐	‐	‐	‐	‐	‐
Limitations in activities of daily living at 1 year ‐ not reported	‐	‐	‐	‐	‐	‐
Limitations in participation at 1 year ‐ not reported	‐	‐	‐	‐	‐	‐
Adverse events	The trial assessing this comparison reported no serious adverse events from routine clinical examination during follow‐up		Not estimable	179 (1 RCT)	‐	‐
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; RCT: randomised controlled trial; RR: risk ratio
GRADE Working Group grades of evidence High quality: We are very confident that the true effect lies close to that of the estimate of the effect Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

Low‐dose corticosteroids compared to short‐course corticosteroids for treating nerve damage in leprosy
Patient or population: people with nerve damage in leprosy (severe type 1 leprosy reaction) Setting: India Intervention: low‐dose corticosteroids (starting at 30 mg/kg/day before tapering to 5 months' completed treatment) Comparison: short‐course corticosteroids (starting at 60 mg/kg/day before tapering to 3 months' completed treatment followed by 2 months' placebo)
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	Number of participants (studies)	Quality of the evidence (GRADE)	Comments
Outcomes	Risk with short‐course corticosteroids	Risk with low‐dose corticosteroids	Relative effect (95% CI)	Number of participants (studies)	Quality of the evidence (GRADE)	Comments
Improvement in sensory nerve function at 1 year ‐ not reported	‐	‐	‐	‐	‐
Improvement in motor nerve function at 1 year ‐ not reported	‐	‐	‐	‐	‐
Change in nerve pain and in nerve tenderness at 1 year ‐ not reported	‐	‐	‐	‐	‐
Limitations in activities of daily living at 1 year ‐ not reported	‐	‐	‐	‐	‐
Limitations in participation at 1 year ‐ not reported	‐	‐	‐	‐	‐
Adverse events	The trial assessing this comparison reported no serious adverse events from routine clinical examination during follow‐up		Not estimable	181 (1 RCT)
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; RCT: randomised controlled trial
GRADE Working Group grades of evidence High quality: We are very confident that the true effect lies close to that of the estimate of the effect Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

High‐dose prednisone compared to low‐dose prednisone for treating nerve damage in leprosy
Patient or population: people with nerve damage in leprosy (ulnar neuropathy due to type 1 or type 2 leprosy reaction) Setting: Brazil Intervention: high‐dose prednisone (starting at 2 mg/kg/day tapering over 6 months) Comparison: low‐dose prednisone (starting at 1 mg/kg/day tapering over 6 months)
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	Number of participants (studies)	Quality of the evidence (GRADE)	Comments
Outcomes	Risk with low‐dose corticosteroids	Risk with high‐dose corticosteroids	Relative effect (95% CI)	Number of participants (studies)	Quality of the evidence (GRADE)	Comments
Improvement in sensory nerve function at 1 year ‐ not reported	‐	‐	‐	‐	‐	Measured by microfilament test but summarised in a composite clinical score
Improvement in motor nerve function at 1 year ‐ not reported	‐	‐	‐	‐	‐	Measured by MRC scale but summarised in a composite clinical score
Change in nerve pain and in nerve tenderness at 1 year ‐ not reported	‐	‐	‐	‐	‐	Measured by visual analogue scale but summarised in a composite clinical score
Limitations in activities of daily living at 1 year ‐ not reported	‐	‐	‐	‐	‐	‐
Limitations in participation at 1 year ‐ not reported	‐	‐	‐	‐	‐	‐
Adverse events	2 participants reported major adverse events, both in the high‐dose group		Not estimable	21 (1 RCT)	‐	‐
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; MRC: Medical Research Council; RCT: randomised controlled trial
GRADE Working Group grades of evidence High quality: We are very confident that the true effect lies close to that of the estimate of the effect Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

Intravenous methylprednisolone and oral prednisolone compared to intravenous normal saline and oral prednisolone for treating nerve damage in leprosy
Patient or population: people with nerve damage in leprosy type 1 reaction of less than 6 months' duration or with new nerve function impairment of less than 6 months' duration Setting: Nepal Intervention: intravenous methylprednisolone and oral prednisolone Comparison: intravenous normal saline and oral prednisolone
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	Number of participants (studies)	Quality of the evidence (GRADE)	Comments
Outcomes	Risk with intravenous normal saline and oral prednisolone	Risk with intravenous methylprednisolone and oral prednisolone	Relative effect (95% CI)	Number of participants (studies)	Quality of the evidence (GRADE)	Comments
Improvement in nerve function Assessed with: Clinical Severity Scale	There was a downward trend in the total Clinical Severity Scores of both groups. There were no statistically significant differences between the prednisolone‐alone and prednisolone plus methylprednisolone groups at any time point		‐	42 (1 RCT)	⊕⊕⊝⊝ low^1,2	The proportion of participants with improvement in motor and sensory nerve function was not reported
Change in nerve pain and in nerve tenderness at 1 year ‐ not reported	‐	‐	‐	‐	‐	‐
Limitations in activities of daily living at 1 year ‐ not reported	‐	‐	‐	‐	‐	‐
Limitations in participation at 1 year ‐ not reported	‐	‐	‐	‐	‐	‐
Adverse events	545 per 1000	551 per 1000 (316 to 955)	RR 1.01 (95% CI 0.58 to 1.75)	42 (1 RCT)	⊕⊕⊕⊝ moderate²	2 people (1 from each arm of the study) experienced at least 1 adverse event
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; RCT: randomised controlled trial; RR: risk ratio
GRADE Working Group grades of evidence High quality: We are very confident that the true effect lies close to that of the estimate of the effect Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect
¹Outcome measure only narratively described. Significant improvement not defined. ²Small sample size, wide CI (imprecision).

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Improvement in sensory score after one year Show forest plot	2		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

1.1 NFI of less than six months' duration	1	75	Mean Difference (IV, Fixed, 95% CI)	0.32 [‐0.91, 1.55]
1.2 NFI of more than six months' duration	1	89	Mean Difference (IV, Fixed, 95% CI)	0.42 [‐0.57, 1.41]
2 Proportion with sensory improvement after one year Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

2.1 NFI of less than six months' duration	1	75	Risk Ratio (M‐H, Fixed, 95% CI)	1.01 [0.81, 1.27]
2.2 NFI of more than six months' duration	1	71	Risk Ratio (M‐H, Fixed, 95% CI)	0.97 [0.65, 1.45]
3 Proportion with serious adverse events Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

3.1 NFI of less than six months' duration	1	75	Risk Ratio (M‐H, Fixed, 95% CI)	0.83 [0.05, 12.77]
3.2 NFI of more than six months' duration	1	92	Risk Ratio (M‐H, Fixed, 95% CI)	1.87 [0.33, 10.64]
4 Improvement in motor score after one year Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

4.1 NFI of more than six months' duration	1	21	Mean Difference (IV, Fixed, 95% CI)	0.12 [‐0.76, 1.00]
5 Proportion with motor improvement after one year Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

5.1 NFI of more than six months' duration	1	3	Risk Ratio (M‐H, Fixed, 95% CI)	4.5 [0.32, 63.94]

	Idioma de la Revisión Cochrane Escoja su idioma de preferencia para las revisiones Cochrane y otros contenidos. Las secciones sin una traducción aparecerán en inglés.

	Idioma de la web Escoja su idioma de preferencia para la web de la Biblioteca Cochrane.

Idioma de la Revisión Cochrane

Idioma de la web

Appendices

Appendix 1. Cochrane Neuromuscular Specialised Register (CRS) search strategy

Appendix 2. CENTRAL search strategy

Appendix 3. MEDLINE (OvidSP) search strategy

Appendix 4. EMBASE (OvidSP) search strategy

Appendix 5. LILACS (BIREME IAHx) search strategy

Appendix 6. CINAHL (EBSCOhost) search strategy

Copiar o descargar referencia

Idioma de la Revisión Cochrane

Idioma de la web

Instituciones a las que se accedió previamente

Usuarios institucionales

Instituciones a las que se accedió previamente

Otras opciones de acceso