Impaired Health-related Quality of Life in PatientsTreated for Wegener’s GranulomatosisMIKKEL FAURSCHOU, LENE SIGAARD, JAKOB BUE BJORNER, and BO BASLUND ABSTRACT. Objective. To investigate whether patients with Wegener’s granulomatosis (WG) experience reduced
health-related quality of life (HRQOL) after accomplishment of remission, and to study the influ- ence of WG-associated organ damage on HRQOL.
Methods. Sixty-eight patients with inactive WG and 680 randomly selected, age- and sex-matched
controls of the Danish background population completed the Medical Outcomes Study Short-Form 36 (SF-36) survey for evaluation of HRQOL. Irreversible organ damage at ributable to WG and/or its treatment was assessed using the Vasculitis Damage Index (VDI).
Results. The median disease duration was 7.5 (range 1–26) years in the WG group, and the median
total VDI score was 2.0 (range 0–7). Compared to controls, WG patients reported impaired HRQOL reflected by significantly lower SF-36 physical component summary scores (PCS) and mental com- ponent summary scores (MCS) (p < 0.001) and by significantly lower scores in 7 out of 8 SF-36 sub- scales (p ≤ 0.001). In the WG group, no statistical y significant correlations were found between the different SF-36 scores and the total VDI score, number of organ systems affected by damage, dis- ease duration, or number of WG relapses. Patients with organ failure or other major forms of dam- age did not report significantly lower HRQOL than less severely affected patients.
Conclusion. WG patients experience significantly reduced HRQOL even in phases with no appar-
ent vasculitis disease activity. Our data indicate that the level of HRQOL does not correlate wel with the extent of vasculitis-associated organ damage in WG. (J Rheumatol First Release August 1 2010; Wegener’s granulomatosis (WG) is a systemic inflammatory forms of vasculitis-associated damage6,7,8. These scoring disease of unknown etiology characterized by granuloma- systems, however, do not provide information on the conse- tous inflammation of the respiratory tract, necrotizing vas- quences of WG as perceived by patients living with the dis- culitis, glomerulonephritis, and the presence of antineu- ease. To our knowledge, the influence of WG on patient- trophil cytoplasmic autoantibodies (ANCA)1,2. The intro- reported health-related quality of life (HRQOL) has been duction of cyclophosphamide-based treatment regimens systematical y investigated in only a few published studies.
improved the prognosis of patients with WG dramatic- Further, data on the relationship between patient-perceived al y1,3,4. Nevertheless, even with modern therapy, the dis- health status and the extent of WG-associated organ damage ease remains associated with significant morbidity. In large are few. Studies based on patients with varied degrees of WG studies, permanent organ damage at ributable to WG or vasculitis disease activity have demonstrated a negative its treatment affected the majority of patients during short- effect of WG on HRQOL9,10,11,12. Comparable observations and longterm fol owup1,5. The cumulative burden of such were made in studies involving WG patients as wel as inflammation- and treatment-induced irreversible tissue patients with other ANCA-associated vasculitides13,14,15.
damage can be analyzed using the Vasculitis Damage Index Seo and coworkers used the Medical Outcomes Study (VDI) or related scoring systems, which quantify different Short-Form 36 (SF-36) survey16,17,18 to evaluate HRQOL in 180 WG patients and found a statistical y significant, From the Department of Rheumatology, Rigshospitalet, Copenhagen inverse correlation between the SF-36 PCS and the VDI University Hospital; and the National Research Centre for the Working score in their cohort5. In contrast, Koutantji, et al did not detect statistical y significant correlations between SF-36 M. Faurschou, MD, PhD; L. Sigaard, Study Nurse, Department of scores and a modified VDI score among 51 patients with Rheumatology, Rigshospitalet, Copenhagen University Hospital; J.B. Bjorner, MD, PhD, Professor, The National Research Centre for the ANCA-associated vasculitides, including 31 WG patients19.
Working Environment; B. Baslund, MD, PhD, Department of We used the SF-36 survey to examine the self-reported Rheumatology, Rigshospitalet, Copenhagen University Hospital. health status of 68 Danish WG patients with inactive vas- Address correspondence to Dr. B. Baslund, Department of Rheumatology, 4242, Rigshospitalet, Copenhagen University Hospital, 9 Blegdamsvej, culitis. The SF-36 scores of the patients were compared to DK-2100 Copenhagen OE, Denmark. E-mail: baslund@rh.regionh.dk SF-36 scores of 680 randomly selected, age- and sex- Accepted for publication May 31, 2010. matched controls of the Danish background population.
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Faurschou, et al. Quality of life in WG Moreover, we analyzed the influence of vasculitis-associat- Table 1. Descriptive data recorded at time of Medical Outcome Study ed organ damage on HRQOL in the WG group.
Short-Form 36 survey for 68 Danish patients with inactive Wegener’s MATERIALS AND METHODS
Study subjects. The Department of Rheumatology at the Copenhagen University Hospital, Rigshospitalet, provides treatment for patients with systemic vasculitides in Eastern Denmark. Patients with inactive WG fol- lowed at the department were invited to participate in the study. Patients receiving treatment with cyclophosphamide, chlorambucil, and/or doses of prednisolone > 10 mg/day were not considered eligible for the study. Out of 75 invited WG patients, 68 (91%) accepted the invitation and completed Median time since WG diagnosis, yrs (range) the SF-36 questionnaire. No patient displayed clinical or laboratory signs Immunosuppressive medication, % of patients of active vasculitis at the time of SF-36 survey, corresponding to a Methotrexate +/– prednisolone therapy (≤ 10 mg/day) Birmingham Vasculitis Activity score (BVAS)20,21 of zero. Al patients met Low-dose prednisolone monotherapy (≤ 10 mg/day) the American Col ege of Rheumatology 1990 criteria for the classification Other drugs* +/– prednisolone therapy (≤ 10 mg/day) Irreversible organ damage at ributable to WG and/or its treatment was evaluated at the time of the study, and the level of damage was scored using Median Vasculitis Damage Index score (range) the VDI data col ection form6,7. Further, we calculated a weighted damage score, in which items of damage of the VDI were scored according to grade of severity, and summed. In this scoring system, we adapted the median damage severity ratings described by Seo, et al, who asked a group of experts to score different forms of organ damage related to WG and micro- scopic polyangi tis on a severity scale from 0 to 10, with 10 representing For each WG patient, 10 age- and sex-matched control subjects were randomly selected among participants in a Danish national health survey conducted in 200524. The participants had been recruited at random from the general population of Denmark by means of the Danish Central Population Register, which holds key information on al citizens of the country. The survey was the fourth of its kind conducted during the period 1987–2005. The purpose of the 4 surveys was to evaluate the health status Median no. organ systems with damage** (range) and analyze factors influencing health and morbidity among adult citizens * Azathioprine (4 patients), mycophenolate mofetil (1 patient).
** Assessed by the Vasculitis Damage Index.
Assessment of HRQOL. HRQOL was evaluated using a validated Danish version of the SF-36 questionnaire25,26. The SF-36 questionnaire contains 36 items that assess HRQOL in 8 health dimensions: physical functioning during the induction phase. The remaining 3 patients had (PF); role physical (RP); bodily pain (BP); general health (GH); vitality received corticosteroid monotherapy as the initial treatment (VT); social functioning (SF); role emotional (RE); and mental health for WG. At the time of the SF-36 survey, 28 patients were (MH). In each dimension, item scores were coded and summed according receiving immunosuppressive maintenance therapy as out- to standard protocols16,17. Scores in the 8 SF-36 subscales range from 0 to lined in Table 1, while 40 patients were fol owed without 100, zero indicating the worst and 100 indicating the best patient-reported health status. Two summary scores, the PCS and the MCS, were derived from the 8 subscale scores as described by Ware, et al18. These summary Compared to controls, the WG patients reported impaired scores were standardized based on US norms so that a score of 50 is the HRQOL reflected by significantly reduced SF-36 PCS and mean score of the US 1998 general population and higher scores indicate MCS and by significantly lower scores in 7 out of 8 SF-36 subscales (Table 2). Patients < 58 years of age (the median Statistical analyses. The Mann-Whitney rank-sum test was used for com- patient age in the cohort) reported somewhat bet er HRQOL parison of continuous data. Spearman’s rank correlation test was used in correlation studies. In al analyses, p < 0.05 defined statistical significance.
than patients ≥ 58 years of age compared to controls. Thus, Analyses were performed using SPSS version 9.0 for Windows (SPSS, while patients ≥ 58 years presented with significantly lower PCS and MCS than controls (p ≤ 0.001 in both compar- isons), younger patients did not display significantly reduced MCS compared with matched controls [mean PCS Basic descriptive data for patients are summarized in Table 47.1 (SD 10.0) vs 53.9 (SD 7.6), respectively; p < 0.001; 1. Fifty-four patients had received oral therapy with mean MCS 52.5 (SD 8.5) vs 54.3 (SD 8.3); p = 0.1].
cyclophosphamide (1–2 mg/kg/day) for induction of remis- Within the WG group, no statistical y significant differ- sion, 2 had been given intravenous cyclophosphamide (0.75 ences in SF-36 summary scores were found between men g/m2 monthly), 6 cyclophosphamide-intolerant patients had and women. Patients who were taking immunosuppressive received oral chlorambucil (2–4 mg/day), and 3 patients had maintenance therapy had significantly lower PCS than been treated with oral azathioprine (1.5–2.0 mg/kg/day). Al patients who were off immunosuppressive medication at the these patients also received high-dose corticosteroid therapy time of SF-36 survey [mean PCS 42.1 (SD 9.7) vs 46.6 (SD Personal non-commercial use only. The Journal of Rheumatology Copyright 2010. All rights reserved.
The Journal of Rheumatology 2010; 37:10; doi:10.3899/jrheum.100167 Table 2. Medical Outcome Study Short-Form 36 survey scores for 68 on WG patients with varied degrees of vasculitis disease Danish patients with inactive Wegener’s granulomatosis (WG) and 680 activity. In our study, we included only WG patients who randomly selected age- and sex-matched controls of the Danish back- were in remission at the time of quality of life assessment.
Our observations add to existing knowledge of HRQOL in WG by showing that patients with the disorder experience compromised self-perceived health status even in phases with no apparent disease activity. Thus, our data substanti- ate findings by Jayne, et al, who observed SF-36 scores below UK norms during clinical remission in a large cohort of patients with ANCA-associated vasculitides (WG or In our cohort, patients ≥ 58 years of age presented with lower SF-36 PCS and MCS than age- and sex-matched con- trols. In contrast, younger patients did not display signifi- Physical component summary score 44.9 (10.5) Mental component summary score 51.5 (9.3) cantly reduced MCS compared to controls. These observa- tions suggest that the negative influence of WG on HRQOL * SF-36 scores for patients and controls were compared using may be particularly pronounced in elderly patients.
Moreover, we observed significantly lower SF-36 PCS for patients who received immunosuppressive maintenance 10.5); p = 0.04]. These subgroups of patients did not differ therapy than for patients who were fol owed without significantly from each other with respect to age, immunosuppressive medication. Since none of the study male/female ratio, years since WG diagnosis, total VDI subjects had active WG at the time of survey, this finding seems to indicate that receiving immunosuppressive therapy Correlation tests revealed no statistical y significant per se may influence HRQOL negatively among patients associations between SF-36 summary or subscale scores and the number of WG relapses, years since WG diagnosis, the Intriguingly, we did not detect significant correlations total VDI score, the weighted damage score, or the number between SF-36 summary or subscale scores and the total of organ systems with damage as assessed by the VDI.
VDI score in our cohort. Statistical y significant, inverse Statistical y significant, weak inverse correlations were correlations were found between the VDI item score for pul- found between 2 SF-36 subscale scores and the VDI item monary damage and the PF and BP SF-36 subscale scores.
score for pulmonary damage (PF: rs = –0.292; p = 0.02. BP: However, the observed correlations are weak, and the possi- rs = –0.298; p = 0.01). We did not detect statistical y signif- bility of chance findings related to multiple testing cannot icant correlations between SF-36 scores and other organ- be ruled out. Of note, our analyses did not reveal significant specific VDI item scores. No significant differences in SF- differences in SF-36 scores between patients presenting 36 scores were observed between patients with major forms with major forms of damage and less severely affected of damage, arbitrarily defined as items of damage of the patients. Further, patients without permanent organ damage VDI assigned a median severity rating of 7–10 by Seo, et as assessed by the VDI did not present with bet er SF-36 al23 (n = 32), and other patients (n = 36). Further, patients scores than other patients. It is interesting that comparable with a VDI score of zero (n = 8) did not differ significantly observations were made in a study from the UK19. Thus, from patients with a VDI score ≥ 1 (n = 60) with respect to Koutantji and coworkers did not detect statistical y signifi- cant correlations between SF-36 scores and the number of damaged organ systems as assessed by the VDI in a cohort DISCUSSION
of patients with different ANCA-associated vasculitides.
Intense cytotoxic and immunosuppressive therapy has trans- Together, these observations suggest that the level of formed WG from a rapidly lethal disorder to a chronic dis- patient-perceived quality of life does not correlate wel with ease, during which prolonged periods of remission can be either the extent or the severity of vasculitis-associated obtained4,27. However, due to recurrent disease flares, grum- organ damage in WG. It might therefore be speculated that bling disease, and side-effects related to treatment, WG the compromised HRQOL experienced by WG patients remains associated with a substantial burden of physical relates primarily to other consequences of living with the morbidity1,5,28,29,30,31,32,33,34,35,36,37. Hoffman and cowork- disease; e.g., development of fatigue and other constitution- ers were the first to demonstrate that WG patients also suf- al symptoms, reduced exercise capacity, social and occupa- fer from impaired self-perceived health status9. This finding tional disability, and fear of recurrent disease was subsequently confirmed in European investiga- flares9,10,11,15,19. Future HRQOL investigations should tions10,11, which like the study by Hoffman, et al were based at empt to elucidate the physical, social, and psychological Personal non-commercial use only. The Journal of Rheumatology Copyright 2010. All rights reserved.
Faurschou, et al. Quality of life in WG factors that affect the self-perceived health status of patients vasculitis associated with antineutrophil cytoplasmic autoantibodies. N Engl J Med 2003;349:36-44.
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The Journal of Rheumatology 2010; 37:10; doi:10.3899/jrheum.100167 34. Faurschou M, Mel emkjaer L, Sorensen IJ, Svalgaard TB, Dreyer 36. Merkel PA, Lo GH, Holbrook JT, Tibbs AK, Al en NB, Davis JC Jr, L, Baslund B. Increased morbidity from ischemic heart disease in et al. Brief communication: high incidence of venous thrombotic patients with Wegener’s granulomatosis. Arthritis Rheum events among patients with Wegener granulomatosis: the Wegener’s Clinical Occurrence of Thrombosis (WeCLOT) Study. Ann Intern 35. Morgan MD, Turnbul J, Selamet U, Kaur-Hayer M, Nightingale P, Ferro CJ, et al. Increased incidence of cardiovascular events in 37. Stassen PM, Derks RP, Kal enberg CG, Stegeman CA. Venous patients with antineutrophil cytoplasmic antibody-associated thromboembolism in ANCA-associated vasculitis — incidence and vasculitides: a matched-pair cohort study. Arthritis Rheum risk factors. Rheumatology 2008;47:530-4.
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