Adjunctive steroid therapy for managing pulmonary tuberculosis

Julia A Critchley; Lois C Orton; Fiona Pearson

doi:10.1002/14651858.CD011370

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Figure 1

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

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Figure 2

Funnel plot of comparison: 1 Steroid therapy comparative to either no therapy or placebo, outcome: 1.2 Sputum conversion by 2 months.

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Figure 3

Funnel plot of comparison: 1 Steroid therapy comparative to either no therapy or placebo, outcome: 1.6 Clinical Improvement at 1 month.

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Figure 4

Forest plot of comparison: 1 Steroid therapy comparative to either no therapy or placebo, outcome: 1.1 All‐cause mortality.

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Figure 5

Forest plot of comparison: 1 Steroid therapy comparative to either no therapy or placebo, outcome: 1.2 Sputum conversion by 2 months.

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Figure 6

Forest plot of comparison: 1 Steroid therapy comparative to either no therapy or placebo, outcome: 1.3 Sputum conversion at 6 months.

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Figure 7

Forest plot of comparison: 1 Steroid therapy comparative to either no therapy or placebo, outcome: 1.4 Treatment Failure.

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Figure 8

Forest plot of comparison: 1 Steroid therapy comparative to either no therapy or placebo, outcome: 1.5 Relapse.

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Figure 9

Forest plot of comparison: 1 Steroid therapy comparative to either no therapy or placebo, outcome: 1.6 Clinical Improvement at 1 month.

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Analysis 1.1

Comparison 1 Steroid therapy comparative to either no therapy or placebo, Outcome 1 All‐cause mortality.

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Analysis 1.2

Comparison 1 Steroid therapy comparative to either no therapy or placebo, Outcome 2 Sputum conversion by 2 months.

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Analysis 1.3

Comparison 1 Steroid therapy comparative to either no therapy or placebo, Outcome 3 Sputum conversion at 6 months.

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Analysis 1.4

Comparison 1 Steroid therapy comparative to either no therapy or placebo, Outcome 4 Treatment Failure.

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Analysis 1.5

Comparison 1 Steroid therapy comparative to either no therapy or placebo, Outcome 5 Relapse.

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Analysis 1.6

Comparison 1 Steroid therapy comparative to either no therapy or placebo, Outcome 6 Clinical Improvement at 1 month.

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Summary of findings for the main comparison. Steroid therapy comparative to either no therapy or placebo for managing pulmonary tuberculosis

Steroid therapy comparative to either no therapy or placebo for managing pulmonary tuberculosis
Patient or population: patients with managing pulmonary tuberculosis Settings: Intervention: Steroid therapy comparative to either no therapy or placebo
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Control	Steroid therapy comparative to either no therapy or placebo
All‐cause mortality	27 per 1000	21 per 1000 (14 to 31)	RR 0.77 (0.51 to 1.15)	3815 (18 studies)	⊕⊕⊝⊝ low^1,2,3,4,5
Sputum Conversion by 2 months	656 per 1000	722 per 1000 (676 to 768)	RR 1.1 (1.03 to 1.17)	1475 (11 studies)	⊕⊕⊝⊝ low^1,3,4,6,7
Sputum conversion at 6 months	Study population		RR 1.01 (0.97 to 1.05)	875 (8 studies)	⊕⊕⊕⊝ moderate^1,3,4,5,6
	911 per 1000	920 per 1000 (883 to 956)
Clinical Improvement at 1 month	Study population		RR 1.16 (1.09 to 1.24)	497 (5 studies)	⊕⊝⊝⊝ very low^1,2,4,8,9
	794 per 1000	921 per 1000 (865 to 985)
The assumed risk* is the mean control group risk across studies. The corresponding risk (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; 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.
¹ Not downgraded for risk of bias: Most of these studies were conducted in the 1960s and provided minimal detail on trial methods. However, the most recent trial from 2005 was well conducted and showed no evidence of clinical benefit with steroids. ² Downgraded by 1 for inconsistency: The overall effect estimate is unduly influenced by two small trials from the 1960s with unusually high mortality rates. One of these trials enrolled severely sick patients who were expected to die within the next few days and found a strong effect in favour of steroids. None of the remaining 16 trials suggest benefit with steroids. ³ Downgraded by 1 for serious indirectness: The majority of these studies are from the 1960s and the result may no longer be applicable to current TB treatment. ⁴ Not downgraded for imprecision: The 95% CI around the absolute effect estimate is sufficiently narrow to exclude clinically important effects. ⁵ Funnel plot symmetry suggests limited risk of publication bias ⁶ Not downgraded for inconsistency: Inconsistency across study results is negligible ⁷ Publication bias is suspected due to the asymmetry in the funnel plot for this outcome. ⁸ Downgraded by 1 for inconsistency: The overall effect estimate is unduly influenced by a single very small trial from the 1960's with extremely polarised rates of clinical improvement in each study arm. ⁹ Publication bias is suspected due to asymmetry identified within the funnel plot for this outcome. Relatively few of the trials identified report upon this outcome and in those which do findings are positive.

Summary of findings for the main comparison. Steroid therapy comparative to either no therapy or placebo for managing pulmonary tuberculosis

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Table 1. Microbiological resolution: conversion

Study ID		Outcome Definition	Culture or Smear (if culture not reported) Negative
Study ID		Outcome Definition	Time point (month)	Steroid	Control	Reported Statistical Significance
Angel 1960		Culture negative; three samples of sputum or gastric washings were sent for culture at start of treatment then at monthly intervals.	Baseline	0/54	0/50	No significant difference
			1	7/34	12/38
			2	25/42	32/47
			3	29/46	39/42	P < 0.001 significantly greater among controls
			4	39/45	41/45	No significant difference
			5	40/44	38/40
			6	45/47	43/46
Bell 1960		Culture negative; 24 hour specimens of sputum were collected until treatment started, then collected monthly. Concentrates prepared by tri‐sodium phosphate method and incubated for 12 weeks.	Baseline	0/45	0/46	No significant difference
			1	16/44	11/45
			2	27/42	25/46
			3	31/41	35/43
Bilaceroglu 1999		Culture conversion rate (Sputum taken twice weekly)	Reported as 'comparable'			P = 0.0794
BTA 1961	BTA ‐ Corticotrophin data	Culture negative; direct smear and culture exam taken monthly and analysed using local lab facilities	Baseline	9/111	5/118	Not reported
			1	36/100	31/109
			3	70/89	77/104
			6	86/87	91/95
			9	67/67	74/74
			12	40/40	39/40
	BTA ‐ Prednisone data	Culture negative; direct smear and culture exam taken monthly and analysed using local lab facilities	Baseline	4/115	5/118
			1	36/109	31/109
			3	80/104	77/104
			6	93/95	91/95
			9	80/80	74/74
			12	45/45	39/40
Horne 1960		Culture negative; direct sputum smear, gastric lavage or laryngeal swabs	1	40/87	28/91	No significant difference
			2	64/87	45/91	P < 0.01
			3	67/87	62/91	No significant difference
			4	75/87	75/91
			5	80/87	82/91
			6	86/87	91/91
			9	75/77	80/80
			12	77/77	80/80
Johnson 1965		Specimens of sputum were collected every two weeks for four months and then every month thereafter Reversal of infectiousness; the first of three consecutive monthly specimens negative for tubercle bacilli on microscopy and culture	2	18/52	11/50	No significant difference
			4	30/52	31/50
			6	38/52	37/50
			8	46/52	42/50
			10	49/52	44/50
			12	48/52	46/50
Malik 1969		Sputum negative; disappearance of sputum in bacilli was monitored for monthly	1	11/46	14/58	No significant difference
			2	26/46	20/58	P < 0.05
			3	28/46	28/58	P < 0.05
			6	35/46	46/58	No significant difference
Marcus 1962		Culture negative; specimens of sputum were collected every two weeks until 2 months then at 3 months and 6 months	1	35/49	31/51	Not reported
			2	40/49	45/51
			3	45/49	45/51
			6	48/49	48/51
Mayanja‐Kizza 2005		Culture negative; sputum cultures obtained at month 1 and 2 and examined for AFB	1	58/93	35/94	P = 0.001
Mayanja‐Kizza 2005			2	80/93	80/94	No significant difference
McLean 1963		Smear or sputum negative; Smear or culture of sputum or gastric aspirate	1	0/13	0/14	No significant difference
			2	3/12	4/14
			3	5/11	8/14
			4	8/12	11/14
			5	8/11	13/13
			6	9/9	10/11
Nemir 1967		Culture from bronchial aspiration and gastric washings on 3 successive morning on admission; culture positive after therapy	During therapy	4/58	2/59	Not reported
Nemir 1967			After therapy	2/58	2/59	Not reported
TBRC 1983	TBRC 1983 ‐ Rif 5/7months	Culture negative; Sputum smears examined by fluorescence microscopy and cultured using a modification of Petroffs method. TB chemotherapeutic with rifampicin for either 5 or 7 months.	1	59/132	70/129	No significant difference
			2	121/132	120/129
			3	1284/132	123/129
	TBRC 1983 ‐ No Rif	Culture negative; Sputum smears examined by fluorescence microscopy and cultured using a modification of Petroffs method.TB chemotherapeutic regimen without rifampicin.	1	46/129	36/140	No significant difference
			2	97/129	104/140
			3	116/129	123/140
USPHS 1965 ‐ 5 week data	USPHS 1965	Culture negative	1	121/426	101/424	Not reported
			2	208/426	220/424	Not reported
			3	316/426	308/424	Not reported
			4	365/426	342/424	Not reported
			5	387/426	374/424	Not reported
			6	389/426	372/424	Not reported
			8	410/426	392/424	Not reported
	USPHS 1965 ‐ 9 week data	Culture negative	1	107/425	101/424	Not reported
			2	202/425	220/424	Not reported
			3	263/425	308/424	Not reported
			4	330/425	342/424	Not reported
			5	368/425	374/424	Not reported
			6	395/425	372/424	Not reported
			8	389/425	392/424	Not reported
Weinstein 1959		Sputum negative; Cumulative sputum conversion	Baseline	16/38	6/33	Not reported
			2	20/38	8/33
			8	33/38	25/33

Table 1. Microbiological resolution: conversion

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Table 2. Microbiological outcomes: treatment failure

Study ID		Outcome Definition	Steroid	Control	Reported Statistical Significance
Angel 1960		Culture positive at 5 months	4/44	2/40	Not reported
BTA 1961	BTA ‐ Corticotrophin data	Culture positive at 6 months	1/87	4/95
BTA 1961	BTA ‐ Prednisone data	Culture positive at 6 months	2/95	4/95
Horne 1960		Culture positive at 5 months	7/87	9/91
Johnson 1965		Culture or smear positive at 6 months	8/50	8/52
Johnson 1965		Study specific indicator, failure to convert by 12 months	2/50	4/52
Malik 1969		Culture or smear positive at 6 months	11/46	12/58
Marcus 1962		Culture or smear positive at 6 months	1/49	3/51
Mayanja‐Kizza 2005		Study specific indicator, not described further	1/93	1/94	No significant difference
McLean 1963		Culture positive at 6 months	0/9	1/11	Not reported
Weinstein 1959		Sputum positive at end of study (6 to 16 months)	2/38	6/33	Not reported

Table 2. Microbiological outcomes: treatment failure

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Table 3. Microbiological outcomes: relapse

Study ID		Method	Steroid	Control	Reported Statistical Significance
Bilaceroglu 1999		Smear or culture positive TB within 3 years follow up	0/91	0/87	Not reported
Johnson 1965		Number readmitted for TB during up to five years of follow up	3/50	10/50	P < 0.05
Mayanja‐Kizza 2005		Those needing re‐treatment up to two years after first regimen of anti‐tuberculous therapy.	8/93	11/94	No difference
TBRC 1983	TBRC 1983 ‐ Rif 5/7months	Two or more of six cultures positive in any three consecutive monthly exams	4/132	3/129	No difference
TBRC 1983	TBRC 1983 ‐ No Rif		3/129	6/140	No difference

Table 3. Microbiological outcomes: relapse

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Table 4. Clinical improvement

Study ID		Outcome Definition	Time Point (months)	Steroid Group	Control Group	Reported Statstical Significance
Angel 1960		Immediate and pronounced non‐specific improvement in general condition reported by nurses and patients	N/A, described as being immeasurable numerically
Bell 1960		Number of participants judged by treating physician to be in 'fair' or 'good' condition as opposed to 'severely ill' or 'poor' condition.	1	44/44	39/46	Improvement from baseline greater in steroid group P < 0.01
Bell 1960			2	42/42	46/46	No difference
BTA 1961	BTA ‐ Corticotrophin data	Number of patients judged by treating physician to have had 'considerable', 'moderate' or 'slight improvement' as opposed to 'no change' or 'deterioration'	1	96/99	100/114	Not reported
			3	91/92	102/107
			6	85/86	94/95
	BTA ‐ Prednisone data	Number of patients judged by treating physician to have had considerable, moderate or slight improvement	1	113/116	100/114
			3	107/108	102/107
			6	98/98	94/95
Johnson 1965		Participants initially with; any degree of cough or sputum, or moderate to severe symptoms, who saw moderate to marked improvement in condition.	10 weeks	39/48	28/46	P < 0.05
Keidan 1961		Participants showing definite‐striking improvement	1	8/8	0/8	Not reported
Marcus 1962		Improvement in 'well‐being and strength'	7 weeks	49/49	48/51	Not reported
McLean 1963		'Rapid symptom response'; method of assessment unclear	Not reported	13/13	1/14	P < 0.0001
Nemir 1967		'Improved'; Method of assessment unclear.	1	23/31	14/31	No difference

			2	10/16	9/18
			3	5/6	3/4
			6	0/1	0/2
			7	0/1	0/1
			time point unclear	39/58	27/59	P < 0.05

Table 4. Clinical improvement

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Table 5. Fever

Author		Outcome Definition	Steroid Group	Control Group	Reported Statistical Significance
Angel 1960		Mean time till patients afebrile, temperature not specified	5 days	19.4 days	Not reported
Bilaceroglu 1999		Mean time till patients afebrile (<37.5°C)	25 days	47 days	Not reported
Bilaceroglu 1999		Mean temperature change 72 hours after treatment initiation	‐1.2 ºC	+ 0.2ºC	P = 0.003
BTA 1961	BTA ‐ Corticotrophin data	Patients with an average temperature of 99°F or more (1 month)	23/100	52/113	Not reported
	BTA ‐ Prednisone data		17/113	52/113
	BTA ‐ Corticotrophin data	Patients with an average temperature of 99°F or more (3 months)	12/92	24/104
	BTA ‐ Prednisone data		36/106	24/104
	BTA ‐ Corticotrophin data	Patients with an average temperature of 99°F or more (6 months)	7/92	10/104
	BTA ‐ Prednisone data		7/106	10/104
Johnson 1965		Median fever duration	1 day	6 days	Not reported
Johnson 1965		Mean fever duration	1 day	13 days	Not reported
Marcus 1962		Mean number of days for temperature to permanently drop below 100°F	1 day	26 day	Not reported
McLean 1963		Mean number of febrile days	2.9 days	10.2 days	Not reported

Table 5. Fever

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Table 6. Weight

Study ID		Outcome	Time Point	Steroid Group	Control Group	Reported Statistical Significance
Angel 1960		Mean gain in weight from baseline (lbs)*	1 months	13	4	Not reported
			2 months	19	8	Not reported
			3 months	24	11	P < 0.001
			4 months	25	13	Not reported
			5 months	26	15	Not reported
			6 months	27	17	P < 0.001
Bell 1960		Mean gain in weight from baseline (lbs)	1 month	2.75	2.13	No statistically significant differences in mean weight of trial arms at any time point.
			2 months	7.56	4.93
			3 months	8.05	8.09
Bilaceroglu 1999		Mean gain in weight (kg)	from day 18 to 70	7.2	4.2	P = 0.0022
BTA 1961	BTA ‐ Corticotrophin data	Mean gain in weight from baseline (lbs)	1 month	12	6	Not reported
			3 months	21	11	Not reported
			6 months	24	17	P = 0.1
			12 months	23	21	P = 0.1
	BTA ‐ Prednisone data	Mean gain in weight from baseline (lbs)	1 month	9	6	P = 0.1
			3 months	26	11	P = 0.1
			6 months	24	17	No statistically significant difference
			12 months	21	21	No statistically significant difference
Horne 1960		Mean gain in weight from baseline(lbs)	1 month	8	6	Not reported
			2 months	17	11
			3 months	21	15
			4 months	21	15
			5 months	21	16
			6 months	21	16
Johnson 1965		Patients initially under 130 lbs who gained 15 lbs or more (n)	2 months	8/23	0/17	P<0.025
		Number of patients initially 15 lbs or more under ideal weight who gained 15 lbs or more by	2 months	9/24	2/21	P<0.05
		Number of patients initially more than 20 lbs under ideal weight who gained 15 lbs or more by	2 months	9/24	2/19	P<0.05
Malik 1969		Mean gain in weight from baseline (lbs)	1 month	8.6	4.4	Not significant
			2 months	12.3	5.1	P<0.05
			3 months	13.3	7.2	P<0.05
			6 months	16.51	11.74	Not significant
Marcus 1962		Mean gain in weight from baseline (lbs)	6 months	25	16	P<0.01
*Read from graph,

Table 6. Weight

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Table 7. Length of hospital stay

Author	Outcome definition	Steroid Group	Control Group	Statistical Significance
Bilaceroglu 1999	Average length of stay for those discharged	53.4 +/‐ 3.1 days	71.3 +/‐ 5.6 days	P=0.0284
Johnson 1965	Average length of stay for those discharged	10 months	11 months	Not reported
Weinstein 1959	Average length of stay for those discharged	188.7 days	207.4 days	Not reported

Table 7. Length of hospital stay

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Table 8. Functional disability

Study ID	Outcome definition	Time point (months)	Steroid	Control	Statistical Significance Reported
Angel 1960	Max expiratory flow rate (body temperature and pressure saturated; litres/minute)	Baseline	189.8 (SD 101.7)	205.1 (SD 114.4)	Significantly higher in the corticotrophin group, no value given
		3	241.1 (SD 137.7)	227.3 (SD 115.4)
		6	238.7 (SD 125.2)	228.4 (SD 100.2)
	Mean vital capacity (maximal inhalation; standard temperature and pressure dry)	Baseline	2,649 (SD 751)	2,523 (SD 838)	Increased to the same extent in both groups, no value given
		3	2,940 (SD 757)	2,728 (SD 790)
		6	2,995 (SD 817)	2,874 (SD 786)
	Max breathing capacity (body temperature and pressure saturated; litres/minute)	Baseline	88.6 (SD 36.3)	82.0 (SD 26.5)	Increased to the same extent in both groups, no value given
		3	102.6 (SD 25.6)	97.8 (SD 32.3)
		6	100.4 (SD 28.7)	99.1 (SD 31.2)
Malik 1969	Abnormal maximal voluntary ventilation	6	12/46	20/58	P < 0.05
	Abnormal maximal voluntary ventilation	12	19/46	20/58	No significant difference
	Abnormal vital capacity	6	14/46	12/58
	Abnormal vital capacity	12	19/46	24/58
	Abnormal maximal expiratory flow	6	17/46	21/58
	Abnormal maximal expiratory flow	12	19/46	24/58
Marcus 1962	Diffusion capacity normal	1	34/49	35/51	No significant difference
		2	34/49	35/51
		3	34/49	36/51
		6	34/49	37/51
	Maximal Mid expiratory flow rate (1/sec)	1	2	2	No significant difference
		2	2.1	2.1
		3	2.1	2.3
		6	2.2	2.3
	Vital capacity normal	1	35/49	36/51	No significant difference
		2	36/49	37/51
		3	36/49	37/51
		6	39/49	40/51
McLean 1963	Lung volumes (6 variables measured)	Not reported	Data not extracted		No significant difference in any of the measures
	Ventilation Effects (6 variables measured)
	Perfusion Effects (6 variables measured)
	Diffusion Effects (3 variables measured)
Park 1997	Mean improvement in forced vital capacity (%)	2	9.2	10.4	No significant difference
Park 1997	Mean improvement in forced expiratory capacity (%)	2	13.1	9.4	No significant difference

Table 8. Functional disability

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Table 9. Adverse events

Author	Outcome definition	Steroid	Control	Statistical significance
Angel 1960	Sepsis, venous thrombosis, mental changes, and partial deafness	Numbers not given, stated equal in each treatment arm.		Not reported
Angel 1960	Hypersensitivity reactions	4/54	8/54
Bell 1960	Hypertension	1/45	0/46
Bell 1960	Toxicity	0/45	0/46
Bilaceroglu 1999	Drug resistance	18/91	Not reported
BTA 1961; BTA ‐ Corticotrophin data & BTA ‐ Prednisone data	Developed co‐morbidities	28/275	13/133
	Chemotherapy regimen changed due to PAS intolerance	3/275	0/133
	Chemotherapy regimen changed due to streptomycin toxicity	6/275	6/133
	Chemotherapy regimen changed due to hypersensitivity reactions	7/275	9/133
Horne 1960	Vestibular disturbance	2/87	5/91
Horne 1960	Hypersensitivity	5/87	4/91
Johnson 1965	Hypertension, diabetes, peptic ulcer, psychosis and infections	Incidence equal in each treatment arm (6%, 4%, 0%, 0%, and 4% respectively)
	Changes to chemo regimen due to hypersensitivity, intolerance, drug resistance and ineffectiveness	29/52	24/50	P < 0.05
	Related respiratory illness (5 years follow up)	11/52	15/50	Not reported
	Acne	23/52	9/50
	Mooning of the face	34/52	8.5/50
	Bronchitis, pneumonia or respiratory insufficiency	4/52	11/50	Not reported
	Hypersensitivity reactions	19/52	7/50	P < 0.025
Marcus 1962	Hypersensitivity reactions	1/49	4/51	Not reported
Mayanja‐Kizza 2005	≥ 1 adverse event	87/93	82/94	P = 0.38
	≥ 1 severe or life threatening event within 3 years	22/93	18/94	P = 0.19
	Candidiasis	32/93	36/94	Not reported
	Hyperglycemia	9/93	3/94	P = 0.036
	Abdominal pain	17/93	13/94	P = 0.47
	Hepatitis	12/93	6/94	P = 0.09
	Fluid retention	28/93	4/94	P < 0.001
	Pruritis	33/93	33/94	P = 0.95
	Herpes simplex	10/93	4/94	Not reported
	Herpes Zoster	16/93	17/94	P = 0.99
	Kaposi sarcoma	0/93	2/94	P = 0.49
	Pneumonia	16/93	16/94	P = 0.93
	Urinary tract infection	14/93	7/94	P = 0.19
	Hypertension	12/93	4/94	P = 0.039
McLean 1963	Number of complications	1/14	5/13	Not reported
	Number of side effects	3/14	13/13
	Rebound phenomena ‐ fever	8/13	0/14
Nemir 1967	Infectious disease	1/19	5/29
	Viral disease	2/19	9/29
	bacterial disease	2/19	3/29
TBRC 1983	Incidence of adverse events	Figures not reported, stated no difference between groups
	Athralgia	Figures not reported, stated no difference between groups
	Swelling of feet or face	62/344	3/339	P = 0.00001
	GI disturbances	21/344	1/339	P = 0.00001
	Induced hyperglycaemia	2/344	0/339	Not reported
USPHS 1965	Severe adverse event requiring discontinuation	2/851	1/424	Not reported
	Hepatitis	4/851	2/424	Not reported
	Sensitivity to Streptomycin‐Pyrazinamide	68/851	22/424	More patients showed intolerance in steroid groups
	Senstivity to Isoniazid‐PAS	38/851	26/424	Not reported
	Blood pressure	No differences in mean SBP or DBP at any time point
	Fasting plasma glucose	No differences at any time points
USPHS 1965 ‐ 5 week data	Acne	14/426	11/424	Not reported
	Moonface	10/426	3/424	Not reported
	Euphoria	6/426	4/424	Not reported
	Oedema	3/426	9/424	Not reported
USPHS 1965 ‐ 9 week data	Acne	17/425	11/424	Not reported
	Moonface	11/425	3/424	Not reported
	Euphoria	11/425	4/424	Not reported
	Oedema	8/425	9/424	Not reported

Table 9. Adverse events

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Table 10. Adverse events only reported for steroid group

Author		Outcome definition	Steroid
Angel 1960		Acne	11/54
		Mooning of face	22/54
		Fluid retention	7/54
		Transient diabetes mellitus	6/54
		DBP over 100 mm	2/54
		Paroxysmal nocturnal dyspnoea	1/54
Bell 1960		Withdrawal phenomena	None
Bell 1960		Mooning of face	None
Bilaceroglu 1999		Steroid side effects	None
BTA 1961	BTA ‐ Corticotrophin data	Steroid therapy changed or stopped	15/111
		Mooning of the face	7/72
		Rebound Phenomena	6/111
		Hypertension	7/111
		Pyschiatric disturbance	6/111
	BTA ‐ Prednisone data	Steroid therapy changed or stopped	7/116
		Mooning of the face	30/116
		Rebound Phenomena	34/116
		Hypertension	6/116
		Glycosuria	10/116
		Pyschiatric problems	2/116
Horne 1960		Marked obesity	3/87
		Hypertension	11/87
		Mooning of the face	18/87
		Hirsuitism	1/87
		Transient glycosuria	6/87
		Transient rash on prednisolone withdrawal	17/87
		Withdrawn from prednisolone therapy	2/87
Marcus 1962		Acute thrombophlebitis	1
		Herpes Zoster	1
		Diabetes	1
		Marked weight gain (23lb)	1
		Moderate Acne	1
Nemir 1967		Temporary elevation of blood pressure	3
		Abdominal distension	7
		Steroid therapy suspended	2
Park 1997		Adverse events	None
Park 1997		Increased infection rate	None

Table 10. Adverse events only reported for steroid group

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Comparison 1. Steroid therapy comparative to either no therapy or placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 All‐cause mortality Show forest plot	18	3815	Risk Ratio (M‐H, Fixed, 95% CI)	0.77 [0.51, 1.15]

2 Sputum conversion by 2 months Show forest plot	13	2750	Risk Ratio (M‐H, Fixed, 95% CI)	1.03 [0.97, 1.09]

3 Sputum conversion at 6 months Show forest plot	10	2150	Risk Ratio (M‐H, Fixed, 95% CI)	1.01 [0.98, 1.04]

4 Treatment Failure Show forest plot	10	1124	Risk Ratio (M‐H, Fixed, 95% CI)	1.02 [0.98, 1.05]

5 Relapse Show forest plot	5	995	Risk Ratio (M‐H, Fixed, 95% CI)	0.61 [0.35, 1.07]

6 Clinical Improvement at 1 month Show forest plot	5	497	Risk Ratio (M‐H, Fixed, 95% CI)	1.16 [1.09, 1.24]

Comparison 1. Steroid therapy comparative to either no therapy or placebo

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