PICO question In patients with glomerulonephritis what are patient preferences and values for immunosuppressive and non-immunosuppressive therapy?

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1 KDIGO GN Guideline update Evidence summary Patient preferences fr glmerulnephritis treatment PICO questin In patients with glmerulnephritis what are patient preferences and values fr immunsuppressive and nn-immunsuppressive therapy? Search strategy and selectin MeSH sub-headings and text wrds assciated with glmerulnephritis, nn-immunsuppressive and immunsuppressive treatment and patient preferences were searched using relevant medial databases fr studies published up t July Search results The search strategy identified 279 relevant citatins, frm these 272 were excluded n the basis f being either the incrrect study design, wrng ppulatin, wrng interventin, and ne was excluded as it was in Spanish and due t a f a lack f resurces we were unable t translate this study. Overall the search fund seven relevant studies. There were a ttal f 708 participants, and studytypes included five crss-sectinal studies, and tw mixed methd studies, using nminal grup technique. All seven studies addressed lupus nephritis. Summary f the main findings Patient and physician preferences fr lupus nephritis treatment Mycphenlate mfetil versus cyclphsphamide Tw studies by De Abreu et al. (1, 2) lked at patient and physician preferences fr treatment ptins fr lupus nephritis. Bth studies had 172 female systemic lupus erythematsus patients frm Brazil and the secnd study had the additin f 202 physicians t cmpare patient t physician preferences. The mean age f the patients was 34 ± 8 years, physicians 31 ±7 years. Seventy-five percent had lupus nephritis, 39.9% f patients and physicians were Caucasian and 60.5% were nn-caucasian. Patients were given infrmatin abut the efficacy and txicity f the tw medicatins (blinded t treatment names t reduce bias) and asked t rank the wrst side-effects, and asked t justify treatment preference. Out f a list f side effects, the three wrst side effects selected by patients were: cancer caused by the drug (44.2%), hair lss (21.6%), and severe infectin (19.1%). Mst patients preferred ral medicatin (mycphenlate mfetil) (68%) rather than intravenus cyclphsphamide. The justificatin fr the preference (patients vs. physicians), were risk (47.7% and 68.9%), effectiveness (12.2% and 2.0%), risk/benefit trade-ffs (2.3% and 22.3%), and practicality (37.8% and 5.9%) (P <0.001). Multivariate analysis suggest that patient decisins were steered by the risk assciated with the drug, cmpared t an effectiveness-based justificatin (OR 31.8; 95%CI 8.2 t 122.9) r a practicality based justificatin cmpared t an effectiveness-based justificatin (OR 6.0; 95%CI 2.5 t 14.2). Patients with prir jint invlvement were less likely t select mycphenlate mfetil, cmpared with patients with n jint invlvement (OR 5.3; 95%CI 1.4 t 19.5). 1

2 Wmens preferences fr cyclphsphamide versus azathiprine Tw studies lked at the preferences f wmen with lupus fr cyclphsphamide r azathiprine using adaptive cnjint analysis (3) and the Health State Scenari Descriptin and Preference questinnaire (4). The study participants were taken frm New Haven, New Lndn, and Danbury, USA. Premenpausal wmen wh wanted mre children were less likely t chse cyclphsphamide cmpared t azathiprine (56% vs. 80%, P= 0.04) (3). Ninety-eight percent f the participants chse azathiprine ver cyclphsphamide when there was an equal prbability f maintaining kidney survival. Of thse initially preferring azathiprine, required prbabilities greater 33% than cnferred by cyclphsphamide after 15 years befre they wuld chse t change medicatins. Thirty-ne per cent were unwilling t switch frm azathiprine t cyclphsphamide fr imprved shrt-term renal survival, and 15% were unwilling t switch t cyclphsphamide even if it ffered maintenance f cmplete kidney survival at 15 years (4). Participants preferred medicatin with high efficacy and lw risk f infectin (each accunting fr 20% f the variatin in preferences) and were cnsidered as imprtant as differences in the prbability f lss f kidney survival (3). Overall there was high individual variability in treatment preferences between participants and 91% preferred a cllabrative rle in their medicatin decisin-making (4). The results fund that thse identified as risk-seeking participants had a preference fr cyclphsphamide, while mre risk-averse patients had a preference fr treatments that were less effective but less txic (5). Barriers & facilitatrs t medicatin decisin-making (nn-specific lupus nephritis medicatin) There were tw relevant studies (6, 7), ne evaluating patients barriers and anther lking at facilitatrs f medicatin decisin-making. These US studies included 52 wmen (mean age 40.6 ±13.3) and used the nminal grup technique (NGT) t acquire bth qualitative and quantitative valuatins. The study tk participants frm tw different centres (eight NGTs at University f Alabama at Birmingham and University f Califrnia, San Francisc clinics) and had included participants with bth lw and high sciecnmic backgrund, including a mix f ethnicity: Caucasian (23%), African American (52%) and Hispanic (25%) participants, this increases the generalizability f the findings. Side-effects were the mst influential barrier chsen by the grups. Seven ut f eight grups selected tw t fur side effect related barriers. Knwn r anticipated side effects had the highest weighted vte (15.4%), fllwed by medicatin expense/ability t pay fr them (8.2%) and the fear that the medicatin culd cause ther diseases (7.8%) fr mst prminent perceived barriers. There was n difference reprted between ethnicities. Participants expressed cncerns abut the impact that medicatin had n physical appearance, the impact n pregnancy, the practicalities f taking medicatins (IV cmpared t ral administratin) affecting a nrmal life. Additinally, the cst f medicatin, and the perceived side-effects f medicatin influenced participant s decisins. Patients generated 35 medicatin decisin-making facilitatrs. Seven key facilitatrs were identified: effective patient-physician cmmunicatin regarding benefits/harms, patients desire t live a nrmal life and cncern fr their dependents, experience benefits including imprved quality f life, symptm relief and few/infrequent harms, and affrdability (7). Grup respnses accrding t ethnicity were unable t be achieved because f the variability f priritized respnses. Hwever, the benefit f effective cmmunicatin with their health-care prvider was brught up in all grups as a key facilitatr. 2

3 References 1. De Abreu MM, Gafni A, Ferraz MB. Develpment and testing f a decisin bard t help clinicians present treatment ptins t lupus nephritis patients in Brazil. Arthritis Rheum. 2009;61(1): de Abreu MM, Gafni A, Ferraz MB. The use f a decisin bard t elicit Brazilian patients' and physicians' preferences fr treatment: the case f lupus nephritis. Value Health. 2011;14(5 Suppl 1):S Fraenkel L, Bdardus S, Wittnik DR. Understanding patient preferences fr the treatment f lupus nephritis with adaptive cnjint analysis.[erratum appears in Med Care May;41(5):574 Nte: Wittink, D [crrected t Wittnik, D]]. Med Care. 2001;39(11): Fraenkel L, Bgardus S, Cncat J. Patient preferences fr treatment f lupus nephritis. Arthritis Rheum. 2002;47(4): Fraenkel L, Bgardus ST, Jr., Wittink DR. Risk-attitude and patient treatment preferences. Lupus. 2003;12(5): Singh JA, Qu H, Yazdany J, Chatham W, Dall'era M, Shewchuk RM. Barriers t Medicatin Decisin Making in Wmen with Lupus Nephritis: A Frmative Study using Nminal Grup Technique. J Rheumatl. 2015;42(9): Singh JA, Qu H, Yazdany J, Chatham W, Shewchuk R. Minrities with lupus nephritis and medicatins: a study f facilitatrs t medicatin decisin-making. Arthritis Res Ther. 2015;17:367. 3

4 21 Aug KDIGO Clinical Practice Guideline fr Glmerulnephritis PICO (10.1) Ppulatin: Females with lupus nephritis - patient preferences Interventin: Mycphenlate mfetil Cmparatr: Cyclphsphamide Outcme Timeframe Study results and measurements Abslute effect estimates Cyclphspha mide Mycphenlat e mfetil Certainty in effect estimates (Quality f evidence) Plain text summary Preference fr medicatin All patients Based n data frm 172 Mst female patients with SLE preferred mycphenlate mfetil cmpared t IV cyclphsphamide. Their justificatin fr medicatins (cmpared t physician) was determined by the risk f therapy (48% vs. 69%), the effectiveness f medicatin (12% vs. 2.0%), risk/benefit trade-ff (2% vs. 22%) and practicality f treatment (38% vs. 6%). All cmparisins were statistically significant (P<0.001). The risk f treatment (OR 31.8, 95%CI 8.2 t 122.9) and the practicality f therapy (OR 6.0, 95%CI 2.5 t 14.2) was cnsidered mre imprtant than the effectivness f treatment fr patients. Lw Patients were blinded t the name f therapies, and preferred MMF ver IV cyclphsphamide. Patients cmpared t physicians placed mre emphasis n the practicality f ral therapy cmpared t IV therapy. The practicality and risk f therapy were cnsidered the mst imprtant factrs in medicatin decisinmaking. Preference fr medicatin Patients with jint invlvment Based n data frm 172 Patients with jint invlvement cmpared t patients with n jint invlvement were less likely t chse mycphenlate meftil ver IV cyclphsphamide (OR 5.3, 95%CI 1.4 t 19.5) Lw Patients with jint invlvement cmpared t patients with n jint invlvement preferred MMF ver IV cyclphsphamide Side-effects Based n data frm 172 In tw brazillain bservatin studies, 172 female patients with lupus nephritis cnsidered the wrst side-effects f treatment with either MMF r cyclphsphamide as cancer (44%), alpecia (22%), and severe infectin (19%). Lw Patients with lupus nephritis emphasised the imprtance f treatment-related sideeffects f cancer, alpecia and severe infectin.

5 21 Aug KDIGO Clinical Practice Guideline fr Glmerulnephritis PICO (10.2) Ppulatin: Females with lupus nephritis - patient preferences Interventin: Cyclphsphamide Cmparatr: Azathiprine Outcme Timeframe Study results and measurements Abslute effect estimates Azathiprine Cyclphspha mide Certainty in effect estimates (Quality f evidence) Plain text summary Patient preferences Equal prbabilty f kidney survival Based n data frm % f patients preferred azathiprine ver cyclphsphamide when there was an equal prbability f renal survival Very Lw Due t serius indirectness 1 The majrity f patients with SLE in these studies f mainly Caucasian, high-incme Americans preferred treatment fr lupus nephritis with azathiprine cmpared t IV cyclphsphamide when there was an equal prbability f kidney survival. This finding may nt be representative f all patients with lupus nephritis. Patient preferences Different prbabilties f kidney survival Based n data frm 265 patients in 3 studies When cyclphsphamide cnferred a 15% imprved shrt-term kidney survival, 31% f patients still preferred azathiprine cmpared t cyclphsphamide. Of thse initially preferring azathiprine, required prbabilities greater 33% than cnferred by cyclphsphamide after 15 years befre they wuld chse t change medicatins. Hwever, 15% were unwilling t switch t cyclphsphamide even if it ffered cmplete kidney survival at 15 years. Very Lw Due t serius indirectness 2 When the prbability f shrt-term r lng-term kidney survival was imprved fr cyclphsphamdie nt azathiprine, 15% f patients were still preferred azathiprine cmpared t cyclphsphamide. Hwever, these findings may nt be representative f the the wider lupus nephritis ppulatin, as they are largely f Caucasian American patients frm high SES bcakgrunds. Patient preferences - Premenpausal wmen wanting children Based n data frm 215 Premenpausal wmen wh wanted mre children were less likely t chse cyclphsphamide cmpared t azathiprine (56% vs. 80%, P= 0.04). Very Lw Due t serius indirectness 3 In premenpausal wmen wh wanted mre children, azathiprine is the preferred therapy ver cyclphsphamide. 1. Indirectness: Serius. Differences between the ppulatin f interest and thse studied, Differences between the ppulatin f interest and thse studied; 2. Indirectness: Serius. Differences between the ppulatin f interest and thse studied; 3. Indirectness: Serius. Differences between the ppulatin f interest and thse studied, Differences between the ppulatin f interest and thse studied;

6 21 Aug KDIGO Clinical Practice Guideline fr Glmerulnephritis PICO (10.3) Ppulatin: Patients with lupus nephrits Interventin: Barriers and facilitatrs t medicatin decisin-making Cmparatr: Abslute effect estimates Outcme Timeframe Study results and measurements Cmparatr Barriers and facilitatrs t medicatin decisinmaking Certainty in effect estimates (Quality f evidence) Plain text summary Barriers Based n data frm 52 patients in 1 studies A representative sample f US patients with lupus nephrits indicated that side-effects were the mst influential barrier t medicatin-decisin making, with knwn r anticpated side-effects having the highest weighted vte using nminal grup technique. Participants explained that this related t its effect n physical apperance, perceived side-effects impact n daily life and its effect n pregnancy and starting a family. Additinally, the cst and practical implicatins f treatment n daily life were cnsidered imprtant barriers t medicatin. Lw In patients with lupus nephritis, side-effects either real r perceive influence there medicatin decisinmaking. With a fcus n its impact n physical appearance and fertility. Csts and the implicatins n daily life (i.e. IV versus ral drug administratin) were als imprtant barriers t medicatin use. Facilitatrs Based n data frm 52 patients in 1 studies A representative US sample f patients with lupus nephritis, using nminal grup technique indicated that key facilitatrs t medicatin decisn-making included: effective patient-physician cmmunicatin regarding benefits and harms, a desire t live a nrmal life and impact n their families/dependents, imprved quality f life, symptm relief and affrability Lw In patients with lupus nephritis, gd cmmunicatin between patient and physician abut benefits and harms and the impact f therapy n everyday life, and their families, as well as affrdability are key facilitatrs t medicatin decisinmaking.