[Supplementary online-only material for Fiest KM, Fisk JD, Patten SB, et al: Fatigue and

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[Supplementary online-only material for Fiest KM, Fisk JD, Patten SB, et al: Fatigue and comorbidities in multiple sclerosis. Int J MS Care. 2016;18(2):96 104.] Supplementary Table 1. Participants reporting fatigue at each visit by the presence of baseline comorbid conditions Comorbidity Participants reporting fatigue, a % (95% CI) Baseline Year 1 Year 2 Lupus 88.9 (46.8-98.6) b 71.4 (29.8-93.6) 80.0 (25.6-97.9) Fibromyalgia 82.4 (65.6-92.0) c 83.4 (66.2-93.2) c 71.9 (53.8-84.8) b Peripheral vascular 78.6 58.3 60.0 disease (49.3-93.3) (29.7-82.3) (34.0-81.4) Glaucoma 78.6 (49.3-93.3) 54.5 (25.7-80.7) 75.0 (43.3-92.2) IBD 77.8 (52.7-91.7) b 76.5 (50.5-91.2) b 80.0 (51.9-93.7) b Depression 77.7 (72.4-82.3) c 71.8 (66.0-76.9) c 68.3 (62.2-73.7) c Anxiety 75.9 (66.9-83.1) c 66.0 (56.1-74.6) c 70.3 (61.1-78.1) c Cataracts 71.4 (55.9-83.1) b 59.5 (44.1-73.3) 61.5 (47.6-73.8)

Rheumatoid arthritis 71.4 (54.3-84.0) b 56.7 (38.5-73.2) 70.4 (50.6-84.7) Diabetes 68.4 (52.0-81.3) 63.4 (47.6-76.8) 69.2 (53.0-81.8) b COPD 67.7 (57.5-76.5) b 68.0 (58.1-76.6) c 61.6 (50.9-71.3) IBS 66.2 (54.7-76.1) 61.6 (50.0-72.1) 74.3 (62.7-83.2) c Thyroid disease 66.2 (54.7-76.1) 51.9 (40.8-62.9) 60.2 (49.3-70.2) Seizure disorder 63.6 (32.5-86.4) 63.6 (32.5-86.4) 75.0 (48.2-90.6) Migraine 63.4 (55.7-70.5) b 70.3 (62.1-77.3) c 59.6 (51.1-67.5) Bipolar disorder 61.5 (33.3-83.7) 57.1 (30.7-80.0) 58.3 (29.7-82.3) Osteoporosis 61.4 (48.1-73.2) 63.9 (51.1-75.0) 63.3 (50.4-74.6) Heart disease 60.7 (41.6-77.0) 58.1 (40.1-74.1) 55.9 (38.9-71.6) Hypertension 60.1 (52.5-67.3) 58.2 (50.9-65.1) 59.7 (52.2-66.7) Hypercholesterolemia 59.3 56.0 55.7

(50.2-67.8) (47.2-64.5) (46.8-64.3) No comorbidity 53.8 (50.6-56.9) 51.3 (48.1-55.6) 51.4 (48.1-54.7) Abbreviations: CI, confidence interval; COPD, chronic obstructive pulmonary disease; IBD, inflammatory bowel disease; IBS, irritable bowel syndrome. a According to the any fatigue definition (Fatigue Impact Scale for Daily Use score 5 vs. <5). b P <.05 compared with no comorbidity. c P <.01 compared with no comorbidity.

Supplementary Table 2. Ordinal generalized estimating equation model of fatigue in four groups over time OR (95% OR adjusted Comorbidity Condition CI) a Exact P value for depressive symptoms Exact P value time interaction P value Any comorbidity Depression 1.65.0005 (1.24-2.18) b 2.58 <.0001 (2.03-3.27) b 1.67 (1.22-2.29) b.0014.99 2.10 (1.54-2.87) bc <.0001.34 IBS 1.71 (1.18-2.48) b.004 1.39 (0.85-2.29).19.23 Migraine 1.69 (1.27-2.27) b.0004 1.51 (1.08-2.13) b.02.61 Anxiety 1.57 (1.15-2.16) b.005 1.27 (0.84-1.91).26.72 COPD 1.37 (0.98-1.92).06 1.25 (0.78-2.00).35.81 Hypertension 1.25 (0.95-1.65).11 1.11 (0.79-1.57).55.43 Thyroid disease 1.23 (0.85-1.78).28 1.30 (0.84-2.01).24.76 Hypercholesterolemia 0.92.59 0.83.38.88

(0.67-1.25) (0.56-1.25) Osteoporosis 0.80 (0.52-1.24).32 0.80 (0.48-1.35).41.76 Abbreviations: CI, confidence interval; COPD, chronic obstructive pulmonary disease; IBD, inflammatory bowel disease; IBS, irritable bowel syndrome; OR, odds ratio. a Adjusted for visit time (continuous), time since symptom onset (years), disability status (Expanded Disability Status Scale score), age, sex, educational level, and the presence of other comorbidities (depression, hypertension, migraine, hypercholesterolemia, anxiety, COPD, IBS, autoimmune thyroid disease, and osteoporosis). b Significant at α = 0.05. c Adjusted for the above variables but only current depressive symptoms (instead of the history/current variable, since this is included).

Supplementary Table 3. Models of change scores with logistic generalized estimating equation of worsening fatigue Condition OR (95% CI) a Exact P value Depression 1.49 (1.08-2.07) b.02 COPD 1.14 (0.75-1.75).54 Osteoporosis 1.07 (0.60-1.92).81 Migraine 1.01 (0.70-1.46).95 Thyroid disease 1.00 (0.63-1.58).99 Hypertension 0.93 (0.65-1.34).70 IBS 0.90 (0.55-1.47).68 Hypercholesterolemia 0.85 (0.57-1.26).41 Anxiety 0.83 (0.53-1.31).42 Abbreviations: CI, confidence interval; COPD, chronic obstructive pulmonary disease; IBS, irritable bowel syndrome; OR, odds ratio. a Adjusted for visit time (continuous), time since symptom onset (years), disability status (Expanded Disability Status Scale score), age, sex, educational level, and the presence of individual comorbidities (hypercholesterolemia, migraine, COPD, IBS, autoimmune thyroid disease, hypertension, osteoporosis, depression, and anxiety). b Significant at α = 0.05.

Supplementary Table 4. Models of change scores with logistic generalized estimating equation of worsening fatigue (same/better vs. worse) in those with/without active symptoms or a history of depression Condition Odds ratio a with depressive symptoms b Exact P value Depression 1.40 (1.01-1.95) c.04 COPD 1.12 (0.72-1.72).62 Osteoporosis 1.07 (0.61-1.89).81 Any comorbidity d 1.14 (0.76-1.72).52 Thyroid disease 1.00 (0.63-1.59).99 Migraine 0.97 (0.67-1.40).87 Hypertension 0.90 (0.62-1.30).57 IBS 0.90 (0.55-1.47).67 Hypercholesterolemia 0.84 (0.57-1.25).39 Anxiety 0.80 (0.50-1.26).34 Abbreviations: COPD, chronic obstructive pulmonary disease; IBS, irritable bowel syndrome. a Adjusted for visit time (continuous), time since symptom onset (years), disability status (Expanded Disability Status Scale score), age, sex, educational level, and the presence of comorbidities (hypercholesterolemia, migraine, COPD, IBS, autoimmune thyroid disease, hypertension, osteoporosis, depression, and anxiety). b Categorized into four groups: no current depressive symptoms, no history of depression; current depressive symptoms, no history of depression; no current depressive symptoms, a history of

depression; both current symptoms and a history of depression. The depression variable was adjusted only for the presence of current symptoms. c Significant at α = 0.05. d Not adjusted for the presence of comorbidities but for all the other aforementioned variables.

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