Graupp M, Hackl G

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Scand J Rheumatol

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Jenette JC et al. Arthritis Rheum. 2013 Jan;65(1):1‐11. 

Wegener´s granulomatosis

• First discribed in 1936• Granulomatous inflammation ofupper (ENT) and lower airways(lungs) > 90% and kidneys in 85%

• Necrotizing vasculitis of small andmedium‐sized vessels

• Aetiology still unknown• 2013: Granulomatosis withPolyangiitis

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Friedrich Wegener, deutscher Pathologe; *4.April 1907 in Varel; †9.Juli 1990 in Lübeck

Wegener´s granulomatosis

Diagnostic criteria

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Wegener´s granulomatosis

2012 Revised International Chapel HillConsensus Conference Nomenclatureof Vasculitides ‐ CHCC

Necrotizing granulomatous inflammationusually involving the upper and lowerrespiratory tract, and necrotizing vasculitisaffecting predominantly small to mediumvessels (e.g., capillaries, venules, arterioles, arteries and veins). Necrotizingglomerulonephritis is common.

• Mean age at diagnosis is around60 years

• Life expectancy around 5 monthsin the 1950s

• Nowadays decades after diagnosis– Cytotoxic drugs

• (Corticosteroids)• Cyclophosphamide

• Untreated, renal failure is fatal• Today long time on dialysis

possible– After receiving kidney transplant

fairly normal life

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Wegener´s granulomatosis

Geetha D et al. Am J Transplant 2007

• To analyse the prognostic factors and causesof death in patients diagnosed withWegener´s granulomatosis over a 20 yearperiod, from 1981 to 2000 in Finland.

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Aim of the study

• Retrospective prognostic study

• Hospital discharge register (National Research andDevelopment Centre for Welfare and Health, STAKES,Finland) screened

• Patients with discharge diagnosis of WG– In specialized medical care– In 1981 – 2000

• 1981 – 1986 based on ICD‐8• 1987 – 1995 based on ICD‐9• 1996 – 2000 based on ICD‐10

• One (!) author ascertained diagnosis– on the grounds of cumulative clinical features– laboratory findings– ACR criteria

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Patients and methods

• What were the key selection criteria?• Diagnosis of WG (ACR)

• Were inclusion criteria appropriate given?• Yes

• Were participants at a common point in thecourse of their disease?

• Yes („de novo“ diagnosis)

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Patients and methods

• Study period from 1 January 1981 to 31December 2000 devided into two subperiods– 1981 – 1990– 1991 – 2000

• End of follow‐up: 30 July 2005• From Statistics Finland information who died bythe end of follow‐up– When WG cause of death, immediate cause of deathwas recorded (if available)

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Patients and methods

• What outcome measures were used?• Date of Death; Cause of Death

• Was follow up time sufficiently long to detectimportant prognostic facors?

• Yes; study period 1981‐2000; end of follow up 2005

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Patients and methods

• Results expressed as– Means (± SD)– Medians (+ IQRs)– 95% confidence intervals

• Groups compared– Mann‐Whitney U‐test– χ2‐test

• Cox Regression used to estimate risk formortality (age and sex adjusted)

• Kaplan Meier curves to visualize survival

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Statistics

• Standardized mortalitiy ratio (SMR)– Ratio between oberseved and expected numbers

• Probabilities of survival (age and sex adjustedsample of general population) calculated fromthe Official Statistics of Finland data

• Ethical aspects adhered

– SMR => Poission distribution ?

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Statistics

Patient´s characteristics• n = 492 (243 men, 249 women)• 83% fulfilled ACR criteria

• ACR neg group older (mean age 57.18 vs. 52.36 years; p

Treatment characteristics• 75.4% (1981 – 1990) and 78.1% (1991 – 2000) treatedwith cyclophosphamide– in females frequently started later (55% vs. 35% 6 or moremonths after first symptoms)

• median cumulative dose smaller for women (32.6 g) than for men(41.6 g)

– 4.3% never received cyclophosphamide

• 87.3% (1981 – 1990) and 93.7% (1991 – 2000) treatedwith glucocorticoids

• 5 treated with TNF‐α blocker• long‐term antibiotic medication use increased tosecond decade (16.7% vs. 28.2%)

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Results

Survival of WG patients• Of the 492 patients, 203 (99 men and 104women) died before the end of June 2005

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Results

Survival of WG patients

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Results

n.s.

n.s.

Predictors of survival

• Older age and elevated creatinine levelshorter survival time

• ENT symptoms and cyclophosphamidebetter outcome

• long‐term antibiotic better prognosis(p< 0.005)

• ANCA‐neg better prognosis than ANCA‐pos (but difference n.s.)

– patients not tested for ANCA had the worstmortality, particularly diagnosed in 19811990 (p< 0.05)

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Results

• Dialysis as predictor– n = 48; increased mortality rate early in disease

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Results

Standardized mortalitiy ratio (SMR) 1981‐2000• All: 3.43 (95% CI 2.98‐3.94)• Women: 4.38 (95% CI 3.59‐5.61)• Men: 2.80 (95% CI 2.28‐3.41)

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Results

• What measures of prognosis & differences betweengroups were reported?

• (1‐) 5 year‐survival rate; HR; SMR

• Could useful estimates of prognosis be calculated?• Yes 

• What was the magnitude and direction of prognosticestimates?

• Older age, renal impairment => poor outcome• ENT and cyclophosphamide => favor prognosis• SMR 3.43

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Results

• Was the source population for participantswell described? Representative?

• Were the characteristics of the study settingwell described? Retrospective study

• Would the prognostic information have animportant impact on patient or practitionerdecisions?

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Study applicability

Thanks for your attention!

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