Table 1. ME/CFS disease characteristics and selected response data, for 29 patients included in the study.
| Supp. Fig.no, CS 1 | Sex, Age 2 | Infection upfront 3 | ME/CFS duration, severity 4 | Previous study 5 | Family AD 6 | Rx infus 7 | Clinical response 8 (weeks) | Response duration 9 (weeks) | Response at study end 10 | Notes 11 | SF-36mean5 raw score 12 , at 0-15-20/24-36m | Function level 13 at 0-15-24-36m |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S4A MajR | F, 24 | Yes, Mono | 8 y, mod | Pilot, Rx,R-Re | No | 6 Rx | 22–156 | 134 | Yes, 36m | LON 34m | 36-nd-99-99 | 10-100-100-100 |
| S4B MajR | F, 46 | Possible | 13 y, mod | KTS-1, Rx,R-Re | Yes | 6 Rx | 16–66, 78–156 | 128 | Yes, 36m | Rx-Wor x1 | 32-100-100-100 | 5-100-100-100 |
| S4C MajR | F, 25 | Yes, Mono | 11 y, mod | KTS-1, Pl,NoR | No | 5 Rx | 16–156 | 140 | Yes, 36m | Airw.inf. | 29-77-76-81 | 20-85-95-95 |
| S4D MajR | M, 21 | Yes, Viral | 8 y, mild | KTS-1, Pl,NoR | No | 6 Rx | 16–156 | 140 | Yes, 36m | 32-59-79-100 | 35-90-95-95 | |
| S4E MajR | F, 28 | No | 12 y, mod | KTS-1, Pl,NoR | No | 6 Rx | 12–156 | 144 | Yes, 36m, SR | LON 22m | 38-89-92-74 | 25-90-100-85 |
| S4F MajR | F, 38 | No | 20 y, mild | KTS-1, Rx,R-Re | No | 6 Rx | 34–46, 50–156 | 118 | Yes, 36m | Rx-Wor x3 | 38-63-72-78 | 15-70-80-90 |
| S4G MajR | M, 26 | Yes Mono | 8 y, mild/mod | No | Yes | 6 Rx | 22–44, 46–70, 74–156 | 128 | Yes, 36m | Rx-Wor x2 | 39-81-83-82 | 25-85-85-85 |
| S4H MajR | F, 56 | Yes, Pneum. | 11 y, mild/mod | No | No | 6 Rx | 8–24, 38–44, 48–104, 130–136 | 84 | No, 36m | 27-81-92-32 | 10-85-85-25 | |
| S4I MajR | M, 59 | No | 3 y, mod/sev | No | Yes | 6 Rx | 36–48, 60–144 | 96 | No, 36m | Rx-Wor x1 | 15-61-61-25 | 5-60-60-30 |
| S4J MajR | F, 42 | Yes, GI | 7 y, sev | No | No | 2 Rx 4 Of | 14–24, 50–60, 64–88 | 44 | No, OoSt 24m | Allergy,BC 24m | 17-58-72-nd | 5-60-75-nd |
| S4K MajR | F, 38 | No | 10 y, mild | KTS-1, Rx,NoR | No | 6 Rx | 20–26, 32–44, 52–72, 78–112 | 72 | No, 36m | Rx-Wor x3 | 15-68-78-21 | 15-75-85-25 |
| S4L MajR | F, 39 | Yes, Airway | 7 y, mod/sev | KTS-1*, Rx,R-Re | No | 6 Rx | 18–24, 28–42, 50–64, 70–86, 92–130 | 88 | No, 32m OoSt 32m | Rx-Wor x6 | nd-nd-nd-nd | 10-90-90-nd |
| S5M MajR | F, 23 | No | 5 y, mod | KTS-1, Rx,R-Re | No | 11 Rx | 26–36, 38–60, 84–100, 114–156 | 90 | Yes, 36m | 36-38-64-88 | 10-75-75-70 | |
| S5N MajR | M, 49 | No | 12 y, mod | KTS-1, Pl,NoR | Yes | 9 Rx | 94–156 | 62 | Yes, 36m | 38-35-44-60 | 10-50-70-72 | |
| S5O ModR | F, 47 | Yes, Mono | 4 y, mod | No | Yes | 10 Rx | 28–42, 46–54, 66–88, 92–144 | 96 | No, 33m | Rx-Wor x3 | 28-37-40-35 | 7-18-30-31 |
| S5P ModR | M, 58 | No | 17 y, mod | KTS-1, Pl,NoR | Yes | 9 Rx | 58–112 | 54* | Yes, 25m OoSt 25m | 35-52-52-nd | 15-40-40-nd | |
| S5Q ModR | F, 44 | Yes, GI | 5 y, sev | KTS-1, Pl,NoR | No | 10 Rx | 64–80, 82–94, 96–102, 112–124 | 46 | No, 32m OoSt 32m | Rx-Wor x3 | 14-30-60-12 | 5-70-70-20 |
| S5R ModR | M, 50 | Possible, Airway | 17 y, mod/sev | KTS-1, Pl,NoR | Yes | 11 Rx | 72–142, 148–156 | 78 | Yes, 36m | Gallstone 33m | 19-26-32-32 | 8-19-32-38 |
| S6U MargR | F, 56 | Yes, Mono | 8 y, mod | KTS-1, Rx,NoR | Yes | 5 Rx | 76–92 | 16** | No, 36m | No sign. response | 26-23-33-29 | 13-17-75-15 |
| S6S NonR | F, 42 | Yes, Borrelia | 5 y, mild | KTS-1, Rx,R-Re | No | 4 Rx | No response | 0 | No, 35m | 33-22-35-58 | 20-25-35-35 | |
| S6T NonR | F, 21 | Yes, Airway | 7 y, mod | KTS-1, Rx,R-Re | Yes | 8 Rx | No response | 0 | No, OoSt 24m | 45-nd-41-nd | 20-65-65-nd | |
| S6V NonR | M, 50 | No | 1 y, mild | No | No | 5 Rx | No response | 0 | No, 36m | *See comment | 21-43-51-44 | 50-70-75-75 |
| S6W NonR | F, 26 | Yes, GI | 3 y, mild/mod | KTS-1, Pl,NoR | Yes | 5 Rx | No response | 0 | No, 36m | Airw.inf, ITP 36m | 21-32-30-30 | 15-20-20-20 |
| S6X NonR | F, 37 | No | 20 y, mod | KTS-1, Pl,NoR | Yes | 5 Rx | No response | 0 | No, OoSt 24m | 23-21-14-nd | 15-15-15-nd | |
| S6Y NonR | F, 32 | No | 9 y, mod/sev | No | Yes | 6 Rx | No response | 0 | No, OoSt 24m | 20-19-19-nd | 8-8-12-nd | |
| S6Z1 NonR | M, 51 | Yes, GI | 8 y, mild/mod | KTS-1, Rx,R-Re | No | 4 Rx | No response | 0 | No, OoSt 12m | MargR KTS-1 | 33-33-nd-nd (0m and 12m) | 20-22-nd-nd (0m and 12m) |
| S6Z2 NonR | F, 49 | Yes, Mono | 13 y, mod | No | No | 5 Rx | No response | 0 | No, OoSt 24m | 30-26-36-nd | 15-15-15-nd | |
| S6Z3 NonR | F, 56 | Yes, Viral | 5 y, sev | No | No | 5 Rx | No response | 0 | No, 36m | 7-9-11-6 | 8-6-4-3 | |
| *See legend | M, 35 | Yes, Throat | 1.5 y, mod | No | No | 1 Rx | nd | OoSt 0m* | Allergy | nd | nd |
1: The numbers refer to corresponding plots in S4, S5 and S6 Figs (i.e. S4A means S4 Fig panel A) for each of 28 individual patients receiving rituximab maintenance treatment. Among 18 patients fulfilling the predefined response criterion, clinical significance (CS) was determined post-hoc as Major (MajR, n = 14) or Moderate (ModR, n = 4). One patient had a marginal response (MargR) and nine patients were non-responders (NonR).
*: one patient (last row in Table 1) had an allergic reaction to the first rituximab infusion and did not receive induction treatment or complete follow-up.
2: F: female, M: male. Age in years.
3: Indicating infection preceding ME/CFS onset. Mono: mononucleosis; Viral: viral infection not otherwise specified; GI: gastrointestinal infection; Airway: upper airways infection; Borrelia: Borrelia infection; Pneum.: pneumonia.
4: ME/CFS disease duration given in years (y). ME/CFS severity categorized as mild: mild grade; mild/mod: mild to moderate grade; mod: moderate grade, mod/sev: moderate to severe grade; sev: severe grade (see Materials and Methods).
5: Previous participation in clinical studies on ME/CFS. Pilot: pilot patient. KTS-1: participated in the KTS-1-2008 study; Pl,NoR: previously given placebo in KTS-1-2008 with no clinical response; Rx,R-Re: previously given rituximab in KTS-1-2008 (or as pilot) with clinical response and later relapse; Rx,NoR: previously given rituximab in KTS-1-2008 with no clinical response; No: the patient had not participated in previous studies. *: this patient (corresponding to S4 Fig panel L) was a participant in KTS-1-2008 and also a pilot patient for this study.
6: Autoimmune diseases (AD) among first-degree relatives were present for 12 out of 29 included patients (41%). These AD included rheumatoid arthritis (in relatives of seven patients), Sjøgren’s syndrome (in relatives of two patients), ulcerative colitis (in relatives of three patients), thyroiditis (in relatives of two patients). Also, glomerulonephritis, lupus, juvenile arthritis, psoriasis, multiple sclerosis (all present in relatives of single patients).
7: Rx infus: number of rituximab (Rx) infusions given to each patient (see Materials and Methods, and Results).
8: Clinical response periods according to predefined criteria, i.e. periods of Fatigue score ≥ 4.5 for at least six consecutive weeks which must include at least one recording of Fatigue score >5.0 during the response period. The numbers show the intervals with clinical response given in weeks during follow-up.
9: Response durations defined as the sum of individual clinical response periods during follow-up, and given in weeks. *: This patient had a moderate improvement from 58–112 weeks, and with a mean Fatigue score exactly 5.0 in the interval 80–112 weeks. He did not fulfill strict response criteria, but was post-hoc judged as a moderate responder.
**: This patient fulfilled predefined response criteria, but had a short lasting and late response period, interpreted post-hoc as probably not related to intervention and not clinically significant.
10: Clinical response status at end of study. Also shown the time of last recording for each patient. Yes: still in clinical response at end of follow-up; No: not in clinical response at end of follow-up; OoSt: out of study, also indicating time point during follow-up; SR: slight symptom increase but still in response;
*: allergic reaction to first rituximab infusion, did not complete induction therapy or follow-up.
11: LON: late onset neutropenia; Airw.inf.: several airways infections; Rx-Wor: indicating number of transient worsening of ME/CFS-symptoms after rituximab infusions; Allergy: allergic reaction to rituximab; BC: breast cancer; ITP: idiopathic thrombocytopenic purpura (also indicated in the corresponding panels in S4, S5 and S6 Figs);
*See comment: this patient had improvement during follow-up assessed by SF-36 scores and selfreported Function level, but did not fulfill criteria for clinical response; MargR KTS-1: this patient had a marginal response duration in the previous KTS-1-2008 study; No sign. response: not interpreted as a clinically significant response.
12: SF-36mean5 is the mean of raw scores for the five SF-36 subdimentions Physical function, Bodily pain, Vitality, General health, and Social function (scales 0–100), shown at 0, 15, 20 or 24, and 36 months follow-up (in three patients last recording at 31, 33 and 35 months, respectively); nd: not done.
13: Self-reported Function level, given as per cent (0–100%) in which 100% denotes completely healthy, according to a form with examples (S3 Fig), recorded at 0, 15, 24 and 36 months follow-up (in three patients last recording at 31, 33 and 35 months, respectively); nd: not done.