Patient Preferences for Subcutaneous versus Intravenous Administration of Treatment for Chronic Immune System Disorders: A Systematic Review

Figures & data

Figure 1 Study selection flow chart.

Abbreviations: PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses; SLR, systematic literature review.

Table 1 Summary of Included Studies Comparing IV Infusion to SC Infusion

Study (Country/Region)	Population	Experience with SC or IV Therapies	Study Design	Patient Preferences
Fasth et al 2007 (Sweden)^Citation18	Children with PID (n = 12) Median age, 10.9 years (range, 1.7–17.1 years) Female, 2 (17%)	Both SCIg and IVIg during study	Open-label switching study: switch from IVIg (in hospital) to SCIg (at home); 6 months of SCIg treatment	Patient/parent preference at end of study: SCIg, 12 (100%)
Gardulf et al 2004 (Austria, Brazil, Germany, Poland, Spain, Sweden)^Citation19	Adults and children with PID (n = 47; adults [≥ 14 years, 32 [68%]; children [< 14 years], 15 [32%]) Adults: median age, 33.5 years (range, 14–74 years); female, 12 (38%) Children: median age, 7 years (range, 3–13 years); female, 0	Both SCIg and IVIg during study	Open-label switching study: switch from IVIg (in hospital) to 10 months of treatment with SCIg (at home, after 4–6 training sessions in hospital); 10 adult patients were on SCIg at enrolment	Preferences at end of study Adult patients on SCIg at enrolment (n = 10), 10 (100%) preferred SCIg treatment at home Adult patients on IVIg at enrolment (n = 22): 16 (73%) preferred SCIg treatment at home; 2 (9%) preferred SCIg but no preference for setting; 2 (9%) preferred treatment at home but no preference for treatment; 1 (5%) preferred IVIg in hospital; 1 (5%) had no preferences Children on IVIg at enrolment (n = 15): 15 (100%) preferred SCIg treatment at home
Misbah et al 2011 (UK, Italy, Switzerland)^Citation21	Adults with MMN (n = 8) Mean age, 57 years (range, 42–66 years) Female, 4 (50%)	Both SCIg and IVIg during study	Open-label switching study: switch from IVIg (in hospital) to SCIg (at home); 24 weeks of SCIg treatment	Choice of ongoing treatment at end of study: SCIg, 7 (100% of patients who completed study)
Samaan et al 2014 (Canada)^Citation24	Children with PID (n = 143) Mean age: switch to SCIg, 10.7 years; stay on IVIg, 11 years; start on SCIg, 6.0 years; start on IVIg, 8.3 years Female: switch cohort, 43%; new cohort, 41%	In one group, patients switched from SCIg to IVIg; in the other group treatment-naïve patients chose SCIg or IVIg	Retrospective analysis of patient therapy choices between IVIg and SCIg: a) patients already on IVIg (n = 51; average follow-up 52 months); b) newly diagnosed patients (n = 92; average follow-up 33 months) ^a	Patients already on IVIg (n = 51): 50 (98%) chose to switch to SCIg and 44 (88%) remained on SCIg during follow-up Newly diagnosed patients (n = 92): 44 (48%) chose SCIg and 95% remained on SCIg during follow-up; 48 (52%) chose IVIg, of whom 73% switched to SCIg during follow-up; at end of follow-up, 74 (80%) were using SCIg
Hoffmann et al 2010 (Germany)^Citation23	Patients with PID/SID (n = 82; preferences, n = 24 adult patients) Mean age, 34 years (range, 1–74 years) Female, 46 (56%)	SCIg during study; 73% had received previous hospital IVIg therapy	Observational study: patients receiving SCIg (at home) treatment; preference reported after 9 months of treatment ^b	Preferences at end of study Treatment: prefer SCIg, 22 (92%); no preference, 2 (8%) Setting: prefer home therapy, 20 (83%); prefer clinic/physician setting, 1 (4%); no preference, 3 (13%)
Desai et al 2009 (USA)^Citation14	Adults and children with PID (n = 11) Mean age, 29 years (range, 5–59 years) Sex NR	Both SCIg and IVIg during study	Randomized crossover study: IVIg (not reported, assumed to be in hospital) vs SCIg (at home); 6 months each treatment	Preferences for ongoing treatment at end of study: SCIg, 10 (91%); IVIg, 1 (9%)
Gladiator et al 2017 (Europe and Brazil)^Citation52 [abstract only]	Adults and children with PID (n = 48) Age and sex NR	Both SCIg and IVIg during study	Open-label switching study: switch from IVIg (not reported, assumed to be in hospital) to SCIg (at home); 12 months of SCIg treatment	Preferences at end of study SCIg, 88% (age ≤ 13 years, 84%; age > 13 years, 91%) Prefer home infusion, 88%
Nicolay et al 2006 (USA, Canada)^Citation20	Adults with PID (n = 44; hospital IVIg, 28; home IVIg, 16) Prior hospital IVIg: mean age, 36.1 years (SD, 13.6 years); female, 11 (39%) Prior home IVIg: mean age, 35.5 years (SD, 13.2 years); female, 6 (38%)	Both SCIg and IVIg during study	Open-label switching study: switch from IVIg (in hospital [n = 21] or at home [n = 13]) to SCIg (at home); 12 months of SCIg treatment	Preferences at end of study Prior hospital IVIg group (n = 21): prefer SCIg, 17 (81%); prefer home therapy, 19 (90%) Prior home IVIg group (n = 13): prefer SCIg, 9 (69%); prefer home therapy, 12 (92%)
Eftimov et al 2009 (Netherlands)^Citation22	Adults with MMN (n = 5) (second cohort described in paper) Median age, 57 years (range, 47–65 years) Female, 0	Both SCIg and IVIg during study	Open-label switching study: switch from IVIg (at home) to SCIg (at home); 6 months of SCIg treatment	Choice of ongoing treatment at end of study: SCIg, 4 (80%); IVIg, 1 (20%)
Permin et al 2009 (Denmark)^Citation53 [abstract only]	Children and adults with immunodeficiency (n = 79; 78 with data) Age ≤ 12 years, 34; 13–18 years, 10; > 18 years, 34 Female, 33 (42%)	SCIg during study; prior IVIg use NR	Open-label prospective observational study; patients or parents asked about preferences after 6 months of SCIg treatment	Preferences at end of study: prefer SCIg, 60 (77%); prefer IVIg, 2 (3%); no preference/not known, 16 (21%)
van Schaik et al 2018 (multinational)^Citation17	Adults with CIDP (n = 172; n = 85 treated with SCIg) Mean age, 55.2–58.9 years across groups Female, 36.0%	Both SCIg and IVIg during study	RCT: IVIg re-stabilization period (up to 13 weeks) followed by randomization to SCIg high or low dose, or to placebo; 24 weeks of randomized treatment	Preferences at end of study: SCIg, 61 (72%); IVIg, 21 (25%); no preference, 3 (4%)
Runken et al 2016 (NR)^Citation54 [abstract only]	Patients with PID (n = 152) Age and gender NR	NR	Survey: online questionnaire; preferences measured using 100-point VAS	Prefer SCIg, 47%; prefer IVIg, 42% Patients strongly preferred their current administration route
Harbo et al 2009 (Denmark)^Citation16	Adults with MMN (n = 9) Mean age, 49 years (range, 28–63 years) Female, 5 (56%)	Both SCIg and IVIg during study	Randomized crossover study: IVIg (in hospital) vs SCIg (at home); each treatment for a period equal to three IVIg treatment intervals of 18–‍56 days	Preferences at end of study: SCIg, 4 (44%); IVIg, 2 (22%); no preference, 3 (33%) Choice of ongoing treatment at end of study: SCIg, 5 (56%); IVIg, 4 (44%)
Chapel et al 2000 (UK, Sweden)^Citation15	Adults with PID (n = 30: UK, n = 10; Sweden, n = 20) Mean age, 44 years (range, 18–67 years) Female, 67%	Both SCIg and IVIg during study	Randomized crossover study: IVIg (at home or in hospital [UK, all in hospital]) vs SCIg (home); 1 year each treatment	Preferences at end of study UK: SCIg, 4 (40%); IVIg, 5 (50%); no preference, 1 (10%) Sweden: SCIg, 6 (30%); IVIg, 11 (55%); no preference, 3 (15%)
Espanol et al 2014 (21 countries outside USA)^Citation26	Adult patients with PID (n = 216) Caregivers of patients with PID (n = 84, 77 aged 1–20 years) Patients: median age, 36 years; female, 128 (59.3%) Patients with caregiver responses: median age, 9 years; female, 29 (34.5%)	Current IVIg, 53% (64% in hospital); current SCIg, 45% (94% at home); other, 2%	Survey – choice-format conjoint analysis; patient preferences for five treatment attributes: Mode of administration (self-administration or administration by a healthcare professional) Frequency of administration (one, two or four times a month) Location (home versus surgery, doctor’s office, clinic or hospital) Number of needle sticks per treatment (one, two or four) Treatment duration (2, 4, or 6 hours)	Both patients and caregivers significantly preferred self-administration to administration by an HCP (p < 0.05) Both groups also significantly preferred (p < 0.05) administration at home, a lower treatment frequency, lower treatment duration and fewer needle sticks per treatment Mode of administration was the least important treatment attribute Patients currently receiving SCIg and their caregivers had a stronger preference for self-administration and treatment at home than those receiving IVIg (both p < 0.05)
Hadden et al 2015 (UK)^Citation25	Adults with MMN (n = 4) or CIDP (n = 4) Mean age, 57.4 years (SD, 13.7 years) Female, 3 (38%)	Both SCIg and IVIg during study	Observational study: patients switching from IVIg (in hospital) to SCIg (at home); preference questionnaire completed after a mean 31 months of SCIg treatment; preference measured with VAS scale	Very strong preference for SC over IV immunoglobulin (VAS mean 93 [SD 12] where 0 = prefer IVIg, 100 = prefer SCIg)
Mohamed et al 2012 (USA)^Citation27	Adult patients with PID (n = 252) Parents of children with PID (n = 66) Patients: mean age, 50.2 years (SD, 13.8 years); female, 189 (75.0%) Parents: mean age, 44.0 years (SD, 7.2 years); female, 55 (83.3%)	Patients: IVIg, 59.9%; SCIg, 40.1%; at home, 60.3%; hospital/clinic, 39.7% Children: IVIg, 43.9%; SCIg, 56.1%; at home, 77.3%; hospital/clinic, 22.7%	Survey – choice-format conjoint analysis; patient preferences for five treatment attributes: Mode of administration (self-administration or administration by a healthcare professional) Frequency of administration (one, two or four times a month) Location (home versus doctor’s office, clinic or hospital) Number of needle sticks per treatment (one, two or four) Treatment duration (2, 4, or 6 hours)	Preferences for aspects of treatment Participants preferred self-administration of SCIg to IVIg administered by an HCP (p < 0.05 for parents; p > 0.05 for adult patients) Preferences for all other aspects of treatment were statistically significant (p < 0.05) toward fewer treatments, treatment at home, fewer needle sticks and shorter treatment duration For both patients and parents, mode of administration was the least important treatment attribute For patients, treatment frequency, number of needle sticks and treatment duration were the most important attributes For parents, treatment frequency was the most important attribute, followed by number of needle sticks and location
Reid et al 2014 (Canada)^Citation28	Patients receiving immunoglobulin treatment (n = 91, including hypogammaglobulinemia [n = 41], antibody deficiency [n = 13] and SCID [n = 6]) Mean age, 23 years (SD, 15 years) Female, 35 (39%) Surveys completed by patients (41), parents (39) or both (5)	All patients on hospital IVIg	25-question survey, including questions on patient choices in the event that home IVIg or home SCIg became available IVIg vs SCIg preferences were assessed using McNemar tests	Patient choices if home IVIg became available: 64% would switch from hospital to home treatment after consulting with their immunologist (p = 0.006) Patient choices if home SCIg became available: 78% would switch from hospital to home treatment after consulting with their immunologist (p < 0.001) IVIg vs SCIg Patients were significantly more likely to switch to home IVIg than to home SCIg (p = 0.01)

Notes: ^aMean vs median not reported. ^bAlthough not explicitly stated, the 24 patients responding to the preference questions are assumed to have prior experience of IVIg.

Abbreviations: CIDP, chronic inflammatory demyelinating polyradiculoneuropathy; HCP, healthcare provider; IVIg, intravenous immunoglobulin; MMN, multifocal motor neuropathy; NR, not reported; PID, primary immunodeficiency; RCT, randomized controlled trial; SCID, severe combined immunodeficiency; SCIg, subcutaneous immunoglobulin; SD, standard deviation; SID, secondary immunodeficiency; TTO, time trade-off; VAS, visual analog scale.

Figure 2 Summary of patient preferences for (A) IVIg or SCIg and (B) IV infusion or SC injection of non-immunoglobulin therapies. Data are patients’ expressed preferences or actual treatment choices (shown in italics). Eight studies in which percentage preferences were not reported were excluded.^{25–28,48–50,58} In some studies not all patients expressed a preference, or preferences were not reported for one alternative; therefore, not all lines add up to 100%.

Table 2 Summary of Included Studies Comparing IV Administration to SC Injection

Study (Country/Region)	Population	Current or Previous Use of SC or IV Therapies	Study Design and Comparators	Results
Gelhorn et al 2019 (USA)^Citation40	Adult patients with severe asthma (n = 47) Mean age, 49.9 (13.1) years Female, 74.5%	Currently on biological therapy, 29 (62%); previous experience of biological therapy, 6 (13%); biologic-naïve, 26%	Survey: telephone interview; questionnaire including preference for SC injection vs IV administration for hypothetical therapy	Preferences for administration route 100% of patients preferred SC injection to IV Preferences for who administers medication 54% of patients preferred administration by HCP in a clinic; 24% self-administration at home; 22% administration by caregiver at home
Sylwestrzak et al 2014 (USA)^Citation44	Adults with TNFi indications (n = 500) ^a Mean (SD) age: IV TNFi users, 49.8 (16.0) years; SC TNFi users, 49.4 (12.2) years; Female: IV TNFi users, 69.3%; SC TNFi users, 67.1%	IV TNFi users, 40.4%; SC TNFi users, 59.6%	Survey: telephone interview including preference for SC injection or IV infusion of TNFi therapy	Preferences for administration route IV TNFi users (n = 202): prefer IV, 71.8% (strongly, 54.5%); prefer SC, 25.7% (strongly, 18.3%) SC TNFi users (n = 298): prefer SC, 90.0% (strongly, 70.8%); prefer IV, 8.1% (strongly, 5.0%) Overall p < 0.001 Preferences among patients with prior experience of other administration route IV TNFi users (n = 48): prefer IV, 65% (strongly, 58%); prefer SC, 35% (strongly, 23%) SC TNFi users (n = 61): prefer SC, 82% (strongly, 62%); prefer IV, 18% (strongly, 10%) Preferences for home treatment IV TNFi users (n = 202): prefer home treatment, 46.0% (strongly, 23.3%) SC TNFi users (n = 298): prefer home treatment, 96.3% (strongly, 94.3%)
Perez et al 2017 (Spain)^Citation62 [abstract only]	Children (< 18 years) with CD (n = 37) Age and sex NR	All patients were initiating TNFi therapy	Retrospective study of patients and families choosing a TNFi therapy	Chose IV infliximab, 4 (11%); chose SC adalimumab, 33 (89%)
Santus et al 2019 (Italy)^Citation41	Adult patients with severe asthma (n = 150) Mean (SD) age, 48.8 (12.1) years Female, 52.7%	48 patients (32.0%) were using SC biologic; 6 patients (4.0%) had prior experience of SC biologic	Survey: paper questionnaire including preference for SC injection or IV infusion of biological therapy	Preferences for administration route Prefer SC, 81.3%; prefer IV, 18.7% Current SC biologic users: prefer SC, 48/48 (100%) Current and prior SC biologic users: prefer SC, 49/54 (91%); prefer IV, 5/54 (9%)
Huynh et al 2014 (Denmark)^Citation33	Patients with RA (n = 142) Mean (SD) age, 57 (14) years Female, 77%	35 patients (24.6%) were biologic-naïve; 107 (75.4%) were treated with IV or SC biologic	Survey: questionnaire including preference for SC injection at home or IV infusion at clinic	Preferences for administration route Biologic-naïve patients: 27/35 (77%) preferred SC at home; 8/35 (23%) preferred IV at clinic (p < 0.01) Patients using biologics: 54/107 (50.5%) preferred SC at home; 53/107 (49.5%) preferred IV at clinic Preference by current administration route Patients on IV (n = 41): 85% preferred IV (p < 0.0001) Patients on SC (n = 66): 71% preferred SC (p < 0.001)
Dashiell-Aje et al 2018 (USA)^Citation51	Patients with SLE treated with belimumab (n = 43) Mean (SD) age, 46.2 (12.2) years Female, 88%	41 of 43 patients were using IV belimumab ^b	Open-label switching study: switch from IV belimumab to SC belimumab using autoinjector; questionnaire completed after 8 weeks	Preferences after 8 weeks (n = 42): prefer autoinjector, 32 (76%); prefer IV, 7 (17%)
Borruel et al 2015 (Spain)^Citation59 [abstract only]	Patients with CD (n = 201) Mean (SD) age, 38.9 (12.3) years Female, 44.3%	NR; patients were candidates for biological therapy	Survey: discrete choice analysis including preferences for SC injection or IV infusion of biologics	Preferences for administration route Prefer SC, 70.1%; prefer IV, 29.9% Preferences for setting among patients preferring SC (n = NR) Prefer home treatment, 68.7%; prefer hospital treatment, 31.3%
Van Deen et al 2020 (Canada, UK, USA)^Citation61 [abstract only]	Patients with IBD (n = 1077) Age and sex NR	NR	Survey: conjoint analysis of different medication attributes including route of administration	SC every 8 weeks vs IV every 8 weeks: prefer IV, 33%; prefer SC, 67% SC every 2 weeks vs IV every 8 weeks: prefer IV, 51%; prefer SC, 49% Experience with SC or IV medication was a strong predictor of preferences for SC or IV, respectively
Fernandes et al 2015 (Portugal)^Citation57 [abstract only]	Adult patients with CD Infliximab group (n = 21): mean (SD) age, 40.4 (10.4) years; female, 43% Adalimumab group (n = 17): mean (SD) age, 35.6 (10.9) years; female, 71%	All patients using SC or IV TNFi therapy	Survey: questionnaire including preference to change to alternative administration method	Patients receiving IV infliximab (n = 21): prefer SC, 53%; prefer IV, 47% Patients receiving SC adalimumab (n = 17): prefer SC, 65%; prefer IV, 35%
Kariburyo et al 2017 (global)^Citation38	Adult patients with IBD (n = 170) Mean age: no discussion, 50.0 years; with discussion, 42.1 years Female: no discussion, 69.0%; without discussion, 65.1%	All patients were biologic-naïve; 83 (48.9%) had discussed biologics with their physician	Survey: online questionnaire including preference for SC injection or IV infusion	Prefer IV, 42.4%; prefer SC, 54.7% Patients who discussed biologics with physician: prefer IV, 39.8%; prefer SC, 59.0% Patients who had no discussion: prefer IV, 44.9%; prefer SC, 50.5%
Desplats et al 2017 (France)^Citation30	Adult patients with RA receiving IV abatacept or IV tocilizumab (n = 201) Mean (SD) age, 58.4 (12.6) years Female, 81.1%	All patients were using IV therapy Majority had previous SC therapy experience (etanercept, 58.5%; mean [SD] number of previous SC treatments, 1.2 [0.9])	Survey: questionnaire including preference for continuing IV therapy or switching to SC	Prefer to continue IV, 45.8%; prefer to switch to SC, 54.2% Patients who preferred to switch to SC were more likely than those wishing to continue on IV to have another ongoing SC treatment (15.9% vs 4.3%; p = 0.016)
Chilton et al 2008 (UK)^Citation46	Adult patients with RA (n = 109) Median age, 65 years Female, 79%	No prior TNFi use	Survey: questionnaire including preference for adalimumab, etanercept or infliximab	Prefer IV infliximab every 2 months, 25 (23%); prefer SC etanercept twice weekly, 4 (4%); prefer SC adalimumab every 2 weeks, 51 (47%); no preference, 29 (27%)
Scarpato et al 2010 (Italy)^Citation35	Adult patients with RA (n = 802) Mean (SD) age, 55.6 (13.1) years Female, 76.9%	Patients using SC or IV drugs were excluded	Survey: paper questionnaire including preference for SC injection at home or IV infusion in hospital	Preferences for administration route Prefer IV at hospital, 50.2%; prefer SC at home, 49.8% Preferences for setting Patients preferring IV (n = 403): 81% prefer hospital administration Patients preferring SC (n = 399): 65% prefer home treatment
Bolge et al 2016 (USA)^Citation29	Adult patients with RA (n = 243) Mean (SD) age, 52.5 (13.1) years Female, 85.2%	Patients were naïve to biologics, but had discussed biological therapy	Survey: online questionnaire about aspects of biological therapy including SC injection vs IV infusion	Prefer SC, 49.3% (strongly, 26.3%); prefer IV, 28.4% (strongly, 11.9%)
Edel et al 2020 (Israel)^Citation31	Adult patients with RA (n = 95) Mean (SD) age, 63.4 (11.9) years Female, 73%	Current SC, 52 (55%); current IV, 24 (25%); current oral, 15 (16%)	Survey: questionnaire including preference for oral, IV or SC treatment	Preferences for administration route Prefer oral therapy, 41%; prefer SC, 43%; prefer IV, 16% Patients who have previous experience with preferred administration route Preferring SC, 40/41; preferring IV, 14/15; preferring oral, 18/39 Preference by current administration route Current SC, 34/52 prefer SC; current IV, 13 of 24 prefer IV; current oral, 13 of 15 prefer oral (all p < 0.001)
Capelusnik et al 2019 (Argentina)^Citation56 [abstract only]	Patients with ASA (n = 70) Median (IQR) age, 46.5 (38–57) years Female, 21%	NR	Survey: questionnaire including preferences for administration route and setting	Preferences for administration route Prefer oral, 51%; prefer SC, 41%; prefer IM, 4%; prefer IV, 3% Preferences for setting Prefer home treatment, 90%; prefer self-administration, 79%
Falanga et al 2019 (Italy)^Citation39	Adult patients with SLE (n = 548) Mean (SD) age, 43.1 (11.6) years Female, 95.6%	28.3% of patients had had a previous prescription for biological therapy (SC vs IV NR)	Survey: online questionnaire including preference for SC injection or IV infusion	Preferences for administration route Prefer SC, 41.2%; prefer IV, 36.9%; do not know, 21.9% Preferences by past experience of biologics No: prefer SC, 40.2%; prefer IV, 33.8%; do not know, 26.0% Yes: prefer SC, 43.9%; prefer IV, 44.5%; do not know, 11.6% (overall p = 0.001 vs ‘No’)
Nagahori et al 2011 (Japan)^Citation55 [abstract only]	Patients with IBD (n = 137) Age and sex NR	All patients were biologic-naïve	Survey: online questionnaire including preference for SC injection or IV infusion	Prefer IV, 81 (59.1%); prefer SC, 56 (40.9%)
Tłustochowicz et al 2013 (Poland)^Citation36	Adult patients with RA (n = 120) Median age, 52 years (range, 20–75) ^c Female, 76.7%	All patients were receiving biologics: IV, 58 (48.3%); SC, 62 (51.7%)	Survey: paper questionnaire including preference for SC injection or IV infusion of biological therapy	Prefer IV, 39.2%; prefer SC, 38.3%; no preference, 22.5%
Grisanti et al 2019 (USA)^Citation42 [survey 1]	Adult patients with AS, PsA or RA (n = 243) ^d Mean (SD) age, 59.8 (12.8) years Female, 76%	44% of patients were biologic-naïve	Survey: paper questionnaire including preference for SC injection or IV infusion of biological therapy	Preferences for administration route Of 54 biologic-naïve patients expressing a preference, 65% preferred IV to SC therapy Preference by current administration route Patients currently on SC therapy (n = NR): prefer SC, 50%; prefer IV, 17% Patients currently on IV therapy (n = NR): prefer IV, 58%; prefer SC, 13%
Adlard et al 2018 (France, Germany, UK, USA)^Citation60 [abstract only]	Adult patients with MS (n = 140) Age range, 21–60 years	NR	Survey: conjoint analysis of preferences for frequency and administration route of MS DMTs	Part-worth preference score: oral administration, 0.475; IV, 0.191; SC, 0.186; overall p < 0.001
Allen et al 2010 (UK)^Citation45	Adult patients with IBD (n = 78) ^e Mean age, 44 years Sex NR	Prior infliximab, 10 (13%)	Survey: questionnaire including preference for IV infliximab in hospital every 8 weeks or SC adalimumab at home every 2 weeks	Prefer IV infliximab, 33 (42%); prefer SC adalimumab, 19 (24%); no preference, 26 (33%) Previous IV infliximab users (n = 10): prefer IV infliximab, 6 (60%)
Cha et al 2017 (South Korea)^Citation37	Adult patients with IBD (n = 322); CD, 46.0%; UC, 54.0% Mean (SD) age, 39.7 (14.2) years Female, 32.6%	157 (48.8%) using TNFi therapies; administration route NR	Survey: questionnaire including preference for IV (in hospital, every 8 weeks) or SC (at home, every 2 weeks) TNFi	Prefer hospital IV every 8 weeks, 58.4%; prefer home SC every 2 weeks: 24.2%
Emadi et al 2017 (Qatar)^Citation32	Patients with RA (n = 294) Mean age: men, 51 years (range, 24–75); women, 48 years (range, 16–84) Female, 75.9%	Current oral therapy, 195 (66.3%); current SC, 64 (21.8%); current IV, 35 (11.9%)	Survey: questionnaire including preference for oral, IV or SC treatment	Preferences for administration route Prefer oral therapy, 69.0%; prefer SC, 23.5%; prefer IV, 7.5% Preference by current administration route Current SC patients: 37/64 (58%) prefer SC Current IV patients: 22/35 (63%) prefer IV
Willeke et al 2011 (Germany)^Citation34 [abstract only; article in German]	Adult patients with RA (n = 102) Mean (SD) age, 59 (11) years Female, NR	All patients were receiving IV rituximab	Survey: questionnaire including preference for SC injection or IV infusion of biological therapy, or for oral therapy	Prefer IV infusion, 65.4% (every 6–9 months, 63.4%; every month, 2.0%); prefer tablets only, 21.5%; prefer SC every 2 weeks, 12.9%
Wu et al 2020 (Brazil)^Citation47	Adult patients with IBD (n = 101) ^f Mean (SD) age, 43.6 (13.5) years Female, 75.3%	All patients were biologic-naïve	Survey: questionnaire including preferences for mode of administration and for treatment profiles based on infliximab and adalimumab	Preferences for administration route Prefer oral, 87.1%; prefer IV, 6.9%; prefer SC, 5.9% Preference for treatment profiles Prefer hospital IV every 8 weeks, 54.5%; prefer home SC every 2 weeks, 45.5%
Bolge et al 2017 (USA, Canada)^Citation43	Adult patients with autoimmune conditions treated with IV biologics (n = 405) ^g Mean age, 50 years (19.3% were aged 65 years or older) Female, 72.8%	All patients were using IV biologics Most patients (68%) had not been able to choose their therapy	Survey: telephone interviews including questions on SC injection vs IV infusion	Prefer IV medication to SC injection, 82%
Boeri et al 2019 (USA)^Citation49	Adult patients with moderate-to-severe UC (n = 200) Mean (SD) age, 42.1 (14.7) years Female, 59.0%	Past or present experience: SC injection, 81 (40.5%); IV infusion, 52 (26.0%)	Survey: discrete choice analysis including preferences for frequency and administration route of UC treatment	Patients preferred oral administration to SC or IV; no significant difference between SC and IV
Bolt et al 2019 (Japan)^Citation50	Adult patients with psoriasis (n = 306) Mean (SD) age, 53.4 (10.7) years Female, 17.6%	NR	Survey: discrete choice analysis including preferences for SC injection or IV infusion of psoriasis treatments	Preferences for administration route SC injections vs IV infusion: coefficient, 0.0762; p = 0.014 Patients with mild disease, 0.1243; p = 0.005; moderate or severe disease, 0.0315; p = 0.477 Preferences for setting Treatment administered by a healthcare professional in a clinical setting, rather than at home: coefficient, 0.3970; p < 0.0001
Husni et al 2016 (USA)^Citation58 [abstract only]	Adult patients with moderate-to-severe RA (n = 510) Mean age, 56.4 years Female, 64.7%	Receiving biological therapy, 45.1% (administration route NR)	Survey: discrete choice analysis including preferences for SC injection or IV infusion of RA treatments	Patients were more likely to select SC than IV administration (OR, 1.69) Preference for oral therapy vs IV: OR, 2.30
Louder et al 2016 (USA)^Citation48	Adult patients with RA (n = 380) Mean (SD) age, 54.9 (9.3) years Female, 81.6%	Patients using biologics were excluded 136 (35.8%) had received injection or infusion of non-RA medication in previous 180 days	Survey: choice-based conjoint analysis including preferences for frequency and administration route of RA therapies	Frequency selected: oral, 75.4%; SC self-injection, 49.2%; IV infusion, 26.3% Utility: oral, +99.3; SC self-injection, +7.3; IV infusion, –106.6 Route of administration was the most important attribute

Notes: ^aIV group: RA, 92; CD, 78; PsA, 23; AS, 15; psoriasis, 12; other, 15. SC group: RA, 151; CD, 77; PsA, 50; psoriasis, 50; AS, 17; other, 14. ^bTwo patients switched from SC belimumab using a pre-filled syringe. ^cAssumed to be median; reported as “average”. ^dRA, 81%; PsA, 13%; AS, 5%. ^eUC, 40; CD, 28; indeterminate colitis, 10. ^fUC, 82; CD, 19. ^gRA, 204; CD, 145; UC, 62; psoriasis, 47; PsA, 41; AS, 9.

Abbreviations: AS, ankylosing spondylitis; ASA, axial spondyloarthritis; CD, Crohn’s disease; DMT, disease-modifying therapy; IBD, inflammatory bowel disease; IM, intramuscular; IQR, interquartile range; IV, intravenous; MS, multiple sclerosis; NR, not reported; PsA, psoriatic arthritis; RA, rheumatoid arthritis; SC, subcutaneous; SLE, systemic lupus erythematosus; TNFi, tumor necrosis factor inhibitor; TTO, time trade-off; UC, ulcerative colitis.

Table 3 Reported Reasons for Preferences

Study (Country/Region)	Main Reasons Given for Patient Preferences
Allen et al 2010 (UK)^Citation45	Prefer IV (n = 33): dislike of idea of self-injecting, 67%; less frequent dosing, 42%; convenience, 36%
	Prefer SC (n = 19): convenience of injecting at home, 79%; no requirement to visit hospital, 63%; less complicated, 53%
Bolge et al 2017 (USA, Canada)^Citation43	Prefer IV (n = 332): dislike of self-injection, 43%; less frequent dosing, 34%; administered by professional, 24%; staff interaction at infusion center, 16%; easier to remember doses, 14%
Capelusnik et al 2019 (Argentina)^Citation56 [abstract only]	Prefer SC (n = 29): easy application, 44.8%; efficacy, 27.6%; safety, 13.8%
Cha et al 2017 (South Korea)^Citation37	Prefer hospital IV every 8 weeks (n = 188): do not like idea of self-injecting, 73%; prefer frequency, 7%
	Prefer home SC every 2 weeks (n = 78): convenience of injecting at home, 73%; no requirement to visit hospital, 8%
Chilton et al 2008 (UK)^Citation46	Patients preferring IV were more likely than those choosing SC to identify contact with other patients and availability of staff as advantages (both p < 0.001)
	Preferring SC was associated with identifying not needing to travel to hospital as an influential factor (p < 0.001)
	Route of administration was not statistically significantly associated with treatment choice
Desplats et al 2017 (France)^Citation30	Prefer IV (n = 92): fear of lack of follow-up with SC route, 72%; lack of medical presence with SC route, 61%; keeping social relationships, 41%; prefer frequency, 33%; fear of adverse events, 28%
	Prefer SC (n = 109): avoid organization difficulty with hospital administration, 72%; greater autonomy, 39%; economic considerations, 22%; technical difficulties with IV infusions, 14%
Falanga et al 2019 (Italy)^Citation39	Patients preferring IV reported that advantages included feeling safe and calm during the infusion, thanks to the assistance of medical staff who are responsible and can intervene in case of side effects.
	Patients preferring SC reported that advantages included the higher comfort and convenience of managing medication at home, and avoiding hospital, with more time for a possible job
Gladiator et al 2017 (Europe and Brazil)^Citation52 [abstract only]	Prefer SCIg (n = 42): highest proportion of “like”/”like very much” responses: “ability to fit treatment into my own schedule” (96%) and “ability to self-administer without medical supervision” (94%)
Huynh et al 2014 (Denmark)^Citation33	Prefer IV (n = 62): safer, 65%; easy to manage, 50%; minimize time, 31%; social contact, 24%
	Prefer SC (n = 80): minimize time, 63%; easy to manage, 43%; more comfortable with self-injections at home, 38%
Nagahori et al 2011 (Japan)^Citation55 [abstract only]	Prefer IV (n = 81): medical staff availability, 83%; prefer frequency, 54%; dislike self-administration, 35%
	Prefer SC (n = 56): simple administration, 79%; home administration, 32%; difficulty visiting clinic, 27%
Reid et al 2014 (Canada)^Citation28	Patients preferred IVIg infusions over SCIg infusions because they take less time (p = 0.005) and did not believe that SCIg infusions 2 times per week are less traumatic than IVIg once per month (p = 0.003)
Runken et al 2016 (NR)^Citation54 [abstract only]	The top reason for preferring IVIg was decreased infusion frequency; the main reason for preferring SCIg was decreased side effects
Santus et al 2019 (Italy)^Citation41	IV administration was associated with less frequent treatment, faster symptom reduction and greater effectiveness
	SC administration was seen as allowing more time for daily activities, with greater convenience and less time managing asthma, but with some practical hassles associated with treatment administration
Scarpato et al 2010 (Italy)^Citation35	Prefer IV at hospital (n = 403): safety of hospital administration, 77%; reassuring effect of doctor’s presence, 67%; prefer frequency, 61%; convenience of hospital treatment, 56%; convenience of administration route, 45%
	Prefer SC at home (n = 399): difficulty of reaching hospital, 97%; convenience of home treatment, 81%; convenience of administration route, 55%; level of interference with everyday life, 42%; easy to use, 36%
van Schaik et al 2018 (multinational)^Citation17	Prefer IVIg (n = 21): works better, 52%; greater independence, 33%; less time needed, 33%; prefer frequency, 33%; fewer side effects, 33%
	Prefer SCIg (n = 61): greater independence, 85%; less time needed, 61%; prefer frequency, 49%; fewer side effects, 48%; works better, 33%
Wu et al 2020 (Brazil)^Citation47	Prefer IV (n = 55): dislike of self-application, 53%; fear of SC injection, 27%
	Prefer SC (n = 46): prefer to take medication at home, 57%; more freedom, 54%

Note: The top five reasons reported by ≥ 5% of respondents are listed.

Abbreviations: IV, intravenous; IVIg, intravenous immunoglobulin; SC, subcutaneous; SCIg, subcutaneous immunoglobulin.

Figure 3 Summary of reported reasons for preferring SC or IV administration. Data are the proportion of studies reporting preferences for SC or IV administration (n = 14 and n = 13, respectively) in which each category was mentioned as a main driver of preferences or reported by ≥ 20% of patients.

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