TABLE I.
Summary of ECP Studies for AID
| Author, year | Study design | Number of pts | ECP schedule | Duration months | Response |
|---|---|---|---|---|---|
| Atopic Dermatitis | |||||
| Prinz 1994 [29] | Case series | 3 | One cycle every 4 weeks, after 12 ECP every 6 weeks | 12 months | 67% CR, 33% PR, ↓, cutaneous inflammation, ↓, IgE |
| Richter 1998 [30] | Case series | 3 | One cycle every 2 weeks | 5 months | 75% improvement, monotherapy |
| Prinz 1999 [31] | Retrospective open clinical trial | 14 | One cycle every 2 weeks | 3 months | 72% OR, normalization of CD4/CD8 |
| Radenhausen 2003 [32] | Retrospective case series | 10 | One cycle every 2 weeks, oral MOP | 5 months | ↓, in SCORAD 87 to 36, ↓, in eosinophilic cationic protein, sIL-2R, sE-Selectin |
| Radenhausen 2004 [33] | Two-center, open clinical trial | 35 | One cycle every 2 weeks, oral MOP | 5 months | 65% OR, ↓, in SCOPAD 74 to 36 |
| Sand 2007 [34] | Single arm, open-label | One cycle every 2 weeks for 20 weeks | 12 months | ↓, in SCORAD 78 to 56 after 10 cycles, improvement in EACT-G, SE36 | |
| Hjuler 2010 [35] | Retrospective case series | 6 | One cycle every 4 weeks to 8 weeks | 67 months | 100% marked improvement, 1CR |
| Rubegni 2013 [36] | Retrospective case series | 7 | One cycle every 2 weeks | 3 months | 85.7% OR, ↓SCORAD, long lasting stabilization in 57% |
| Wolf 2013 [37] | Prospective | 10 | One cycle every 2 weeks | 5 months | 30% MR, SCOPAD ↓, 65 to 55, no change in SKINDEX, SE-36, FACT scores |
| Summary, Median, range | 9 | 95 3–35 |
One cycle every 2 weeks | 5 3–67 |
84 30–100 |
| Oral lichen planus | |||||
| Gerber 1997 [38] | Case report | 1 | 12 cycles | 6 months | CR |
| Becherel 1998 [39] | Open prospective | 7 | One cycle every 2 weeks, 24 cycles | 12 months | 100% CR after 1.5Mo |
| Kunte 2005 [40] | Case series | 4 | One cycle every 2 weeks | 10 months | 100% nearly CR, Clinical sustained improvement after discontinuation |
| Guyot 2007 [41] | Case series | 12 | Initially one cycle every weeks for 3 weeks, 21 cycles | 11.5 months, (1–36) | 75% CR, 25% PR, Monthly evaluation, recurrence in 11 pt, ↓, lymphocytes in responders |
| Elewa 2011 [42] | Case report | 1 | 6–12 cycles | 6 months | Reduction of ulcers 80% |
| Toberer 2012 [43] | Case report | 1 | 14 cycles, every 2 weeks, after 3mo | 6 months | CR |
| Marchesseau-Merlin 2008 [44] | Case series | 2 | 9, 20 | 75%, Stabilization with subjective improvement, Flare after discontinuation | |
| Summary Median, range | 7 | 28 1–12 |
One cycle every 2 weeks | 6 | 100% |
| Epidermolysis Bullosa Acquisita | |||||
| Rook 1989–90 [45], [46] | Case series | 4 PV | One cycle every 4 weeks, after 7 ECP every 5 weeks | 2 years | 75% CR, Antibody titer ↓, 1280 to 40, Discontinuation of medication |
| Liang 1992 [47] | Case report | 1PV | One cycle every 2 weeks for 2ECP every 3 weeks | 70% OR | |
| Gollnick 1993 [48] | Case report | 1PV | One cycle every 4 weeks | Near CR | |
| Miller 1995 [49] | Case report | 1 | One cycle every 3 weeks | 2 months | Clinical improvement |
| Owsianowski 1996 [50] | Case report | 1 | One cycle every 4 weeks | Clinical improvement | |
| Gordon 1997 [51] | Prospective | 3 | One cycle every 3 weeks | 5 months | 100% objective sustained clinical improvement |
| Azana 1997 [52] | Case report | 1 | One cycle every 4 weeks | 15 months | CR after 5cycle, AB titer ↓, 1000–0, Discontinued IS, sustained response |
| Camara 1999 [53] | Case report | 1 | One cycle every 3 weeks | 24 months | Clinical improvement |
| Wollina 1999 [54] | Case series | One cycle every 4 weeks | 4–42 months | Clinical improvement | |
| Sanli 2010 [55] | Retrospective longitudinal | 8 PV/3EBA | One cycle every 4 weeks, 21–51 cycles | 20 months months | PV in 100% OR after two to six cycles, EBA 2CR, 1PR. Less effective in patients with high autoAB and as monotherapy. Steroid taper |
| Summary Median, range | 10 | 31 1–11 |
One cycle every 4 weeks | 20 1–32 |
100 70–100 |
| Systemic Sclerosis | |||||
| Rook 1989 [56] | Case series | 2 | One cycle every 2 weeks | 12 months | 1CR, 1PR |
| Rook 1992 [57] | Pospective, randomized, single-blind | 31 | One cycle every 4 weeks | 6–10 months | At 6mo: 68% skin vs 32%, 10mo: 69% vs 50%, no difference after 10Mo |
| Cribier 1995 [58] | Open | 9, 2 morphea | One cycle every 2 weeks | 6 months | Unchanged in 3 (38%), aggravated in 38%, progression in 13%, 50% OR morphea |
| Owsianowski 1996 [50] | Retrospective | 10 | One cycle every 4 weeks | 24 months | 50% OR |
| Schwartz 1997 [59] | Retrospective | 5 | One cycle monthly | 59 months (6–21) | 100% Improvement/stabilization in joint mobility |
| Krasagakis, 1998 [60] | Prospective | 16 | One cycle every 4 weeks | 6–5 months | OR 38%, mixed 13%, stable 19%, |
| Enomoto 1999 [61] | Prospective multicenter, randomized crossover. | 19 | One cycle every 4 weeks | 12 months | 5.4% skin improvement. |
| Muellegger 2000 [62] | Single center observational study | 11 | One cycle every 4 weeks | 16–57 months | 45% OR in skin changes and physical performance. Progression in extracutaneous (91%) and QoL (82%) |
| Reich 2003 [63] | Observational | 20 | One cycle every 4 weeks | 12 months | 55% (30%PR, 25% stable). Responders had short PSS-course, moderate ANA titre, normal TNE-alpha, lack of Scl-70 |
| Hashikabe 2005 [64] | Observational | 13/11 ECP | 2 only oral MOP, ointment | Mean 15days | improvement in dermal edema, not fibrosis |
| Knobler 2006, [65] | Multicenter randomized double-blind, placebo-controlled | 27 | One cycle every 4 weeks | 6–12 months | improvement in skin severity, joints; but not between the therapy arms, ↓, in new joints involvement |
| Papp 2012 [66] | Open study with controls | 16 | One cycle in 6 weeks | 9 months | Improve in joints, mobility, ↓, of dermal thickness, ↓, Th17, ↑ Tregs |
| Summary Median, range | 12 | 179 2–31 |
One cycle every 4 weeks | 11 0.5–59 |
60 5.4–100 |
| Systemic Lupus Erythematosus | |||||
| Knobler 1992 [67] | Pilot study | 8 | One cycle monthly | 6 months | 88% OR, ↓, in clinical activity score from 7 to 1 |
| Richter 1998 [68] | Case report | 1 | One cycle monthly | 6 months | CR |
| Wollina 1999 [69] | Case series | 2 | 6–9 cycles | 6 months | CR for 18 and 11 Mo |
| Richard 2002 [70] | Case report | 1 | One cycle monthly | 9 months | OR, but not sustained |
| Morruzzi 2009 [71] | Case series | 4 | Two cycles | 1 months | 50% CR, 50% PR |
| Boeckler 2008 [72] | Case report | 1 | One cycle every 2 weeks | 2 months | CR |
| Summary Median, range | 6 | 17 1–8 |
One cycle monthly | 6 1–9 |
100 88–100 |
| Nephrogenic Systemic Fibrosis | |||||
| Lauchli 2004 [73] | Case report | 1 | Four cycles | Improvement of induration | |
| Gilliet 2005 [74] | Case series | 3 | One cycle every 2–4 weeks | 6 months | 100% improvement skin softening, joint motility (1CR) |
| Richmond 2007 [75] | Case series | 5 | 34 ECP, every 2–3 weeks in 4 pts, 1 pt weekly | Mean 8.5 months | 60% mild benefit in skin tightening, range of motion, functional skin thickening, joint capacity, PET, functional index |
| Mathur 2008 [76] | Case series | 3 | One cycle every 2 weeks | 6 months | 100% clinical improvement |
| Summary Median, range | 4 | 12 1–5 |
One cycle every 2 weeks | 6 6–9 |
100 60–100 |
| Multiple Sclerosis | |||||
| Poehlau 1997 [77] | Case series | 2 | One cycle every 4 weeks, MOP oral | 4y, 1y | ↓, in relapses from 11 to 1 |
| Rostami 1999 [78] | Double blind, placebo-controlled | 16 | One cycle every 4 weeks | 12 months | No difference in EDSS, Ambulation index, Scripp’s |
| Besnier 2002 [79] | Hot study | 4 | 1 ECP Weekly for 6 weeks, monthly for 6Mo | 6 | OR 80% (1PR, 3Stable), 1 Worse. Kurzke, EDSS by independent neurologist |
| Cavaletti 2006 [80] | Pilot study | 5 | One cycle every 2 weeks for 4Mo, 2ECP every 4 weeks for 6mo, 2ECP every 8 weeks for 12Mo | 24 months, 102 ECP | ↓, in relapse rate, EDSS, MRI stabilization |
| Summary Median, range | 4 | 28 | One cycle every 4 weeks | 12 6–24 |
90 0–100 |
| Diabetes Type 1 | |||||
| Ludvigsson 2001 [81] | Randomized double-blind placebo controlled | 19 | Five cycles | 3 months | ↓, insulin need, No difference in HbAlC, weeks eak effect on disease process |
| Ernerudh 2004, [82] | Randomized double-blind placebo controlled | 19 | Five cycles | 3 months | No clinical, cellular difference; increased activated T cells in placebo |
| Faresjo 2005 [83] | Randomized double-blind placebo controlled | 10 | Five cycles | 3 months | Protective role of ECP, ↓, of IFN-g, increase in IL-4 in ECP arm |
| Jonson 2008 [84] | Randomized double-blind placebo controlled | 19 | Five cycles | 3 months | Increase of CD4,CD8, ↓, in CTLA4, TGF-b mRNA in sham arm |
| Summary Median, range | 4 | 29 10–19 |
Five cycles | 3 | n/a |
| Crohn’s disease | |||||
| Reinisch 2001 [85] | Prospective pilot study | 9 | 6 months | OR 44% with discontinued steroids, 44% ↓, steroids (>50%), intestinal homing of ECP-treated cells | |
| Guariso 2003 [86] | Case series | 2 | 22 ECP, Weekly | 3 months | No change |
| Bissaccia 2007 [87] | Prospective | 2 | 30 ECP, every 4 weeks | 6 months | Clinical response for moderate, active refractory disease |
| Abreu 2009 [88] | Multicenter prospective | 28 | Week 1–4: twice weekly, every week; Week 5–12: twice weekly, every other weeks, | 3 months | 50% response CDAI (75% maintain response at 2y), 60% fistula closure |
| Reinisch 2013 [89] | Prospective open-label, multicenter | 31 | 12 ECP | 6 months | 23% discontinued steroids, sign. ↓, of steroids, 10% remain in CR 48 Weeks after ECP |
| Summary Median, range | 5 | 72 2–31 |
One cycle every 4 weeks | 6 3–6 |
33.5 0–50 |
| Rheumatoid Arthritis | |||||
| Malawista 1991 rom | Pilot study | 7 | One cycle monthly | 6 months | 57% OR |
| Vahlquist 1996 [91] | Open study | 8 | One cycle every 2 weeks | 6 months | 50% PR, significant (74%) decrease in the Ritchie articular index, ↑ CD4:CD8 ratio in responders prior ECP |
| Bracaglia 2008 | Case report | 1 | One cycle every week | 4 months | Mo response, no Tregs changes |
| Summary | 3 | 16 | 6 | 36 0–57 |
|
| Deep Morphea, Psoriasis | |||||
| Vonderheid 1990 [92] | Case series | 4 | One cycle every 2 weeks | 6–13 months | 100% clinical improvement PR, flare after discontinuation of Mtx, |
| Neustadter 2009 [93] | Case report | 1 | One cycle every 2 weeks, every 3.4 weeks | 6 months | Clinical improvement within 1–2 months |
| Summary Median, range | 2 | 5 1–4 |
One cycle every 2 weeks | 6 | n/a |
Abbreviations used: MR, minimal response; One cycle = two ECP treatments; OR, overall response; CR, complete response; PR, partial response; sign significant, PV, pemphigus vulgaris; CDAI, Crohn’s disease activity index; W, week; Mo, month; ECP, extracorporeal photopheresis; n/a, not applicable; ↓ decreased, autoAB autoantibodies.
Definition of studies: Case report – is a clinical observation of diagnosis, treatment, follow-up etc without casual conclusions on effectiveness of the intervention. Case series – is a group of cases, without or with controls (case–control observational study), or literature/historical controls involving patients under similar treatment and including clinical descriptive analysis. Open clinical trial is a study where participants know about administered medication. Retrospective study is a longitudinal analysis of patient’s history. Prospective study is a longitudinal observation of newly enrolled patients. Randomized controlled study is a prospective investigation of active experimental intervention with random and equal assignment of patients or controls. Cross-sectional study evaluates the relationship between ECP treated and not treated groups of patients with the defined disease at one specific time point over a short period of time. Longitudinal study is a correlational research including repeated observations of the same variables over prolonged period of time to record the clinical outcome. Observational study includes ECP patients which were passively observed during the treatment to record the clinical outcome but lacking a casual association. Pilot study is a conducted preliminary small scale study to evaluate feasibility, duration, patient size and potential effectiveness in order to prepare a further larger study.