Kreuter 2006.

Methods	This was a prospective, randomised, 3‐arm comparison trial with active controls, conducted at a German university hospital. The aim of this study was to compare the safety and efficacy of low‐band (LD) UVA1, medium‐band (MD) UVA1, and narrowband (NB) UVB phototherapy in the treatment of morphea.
Participants	Participants were recruited from dermatologic outpatient clinics from 2004 to 2005. Inclusion criteria: diagnosis of morphea established according to accepted clinical and histopathologic features, plus signs of active disease expressed by increasing size of lesions, appearance of new lesions, and/or clinical signs of inflammation within 3 months prior to the study. Exclusion criteria: pregnancy or lactation, any internal immunomodulating or immunosuppressive therapy within the last 4 weeks before treatment, any topical therapy within the last 2 weeks before treatment except the use of emollients, use of potentially photosensitising drugs, and a history of photosensitising dermatoses. Number of patients randomised: 64 (27 group 1 + 18 group 2 + 19 group 3) Number of participants analysed: 62 (27 group 1 + 17 group 2 + 18 group 3) Women: 54 (22 group 1 + 17 group 2 + 15 group 3) Men: 10 (5 group 1 + 1 group 2 + 4 group 3) Age: from 5 to 73 years old; mean age in group 1 was 36.2 ± 21.7 years (5 to 73), 43.7 ± 16.1 years (19 to 73) in group 2 and 47.7 ± 19.8 years (15 to 73) in group 3. Ethnicity: all included participants were white and had skin type II or III. Morphea type: circumscribed morphea (52), linear scleroderma (4), en coup de sabre (4), and generalised (3) subtype. 1 participant had en coup de sabre with coexisting circumscribed morphea (mixed type). Length of illness: from 5 months to 39 years; 4.4 ± 3.8 years (1 to 14) in group 1, 4.9 ± 5.1 years (1 to 19) in group 2 and 7.9 ± 9.4 years (1 to 39) in group 3. Participant's prior treatments: In 43 participants, prior treatment (topical steroids, n = 20; topical calcipotriol, n = 5; systemic steroids, n = 13; methotrexate, n = 5; cyclophosphamide, n = 1; azathioprine, n = 1; hydroxychloroquine, n = 2; penicillin, n = 8) had not resulted in a sufficient improvement. A total of 21 participants had not previously been treated for morphea.
Interventions	Group 1: a. Therapy and dosage: exposure of 20 J/cm² LD UVA1 in a bed emitting wavelengths mainly from 340 nm to 400 nm. The irradiation at body distance was 24 mW/cm² resulting in a dose of 1.44 J/min/cm². The average time of exposure for applying 20 J/cm² was about 15 minutes. Phototherapy was performed 5 times a week for a total of 40 treatment sessions, resulting in a cumulative dose of 800 J/cm². b. Administration: topical c. Duration of treatment: 8 weeks d. Follow‐up after treatment: 3 months Group 2: a. Therapy and dosage: exposure of 50 J/cm² MD UVA1 in a irradiation equipment emitting wavelengths from 340 nm to 530 nm. The irradiation at body distance was 28 mW/cm² resulting in a dose of 1.68 J/min/cm². The average time of exposure for applying 20 J/cm² was about 30 minutes. Whole body irradiation was performed 5 times a week for a total of 40 treatment sessions, resulting in a cumulative dose of 2000 J/cm². b. Administration: topical c. Duration of treatment: 8 weeks d. Follow‐up after treatment: 3 months Group 3: a. Therapy and dosage: exposure to NB UVB phototherapy in a cabin fitted with fluorescent lamps that emit wavelengths between 310 nm and 315 nm with a peak at 311 nm. Starting dose was 0.1 J/cm² NB UVB for skin type II and 0.2 J/cm² for skin type III. Depending on tolerability and skin type, NB UVB dosage was increased with 0.1 to 0.2 J/cm². Maximum NB UVB dose was considered 1.3 J/cm² for skin type II and 1.5 J/cm² for skin type III. Irradiation was performed 5 times a week. b. Administration: topical c. Duration of treatment: 8 weeks d. Follow‐up after treatment: 3 months Groups 1, 2 and 3: Participants wore eye goggles as protection against UV radiation. Additional therapy was restricted to the use of emollients (not specified) that had been used according to a standard protocol and had been applied once daily in the evening. Emollients were not applied shortly (1 hour) before or after phototherapy to avoid any alteration of UV transmission.
Outcomes	Primary outcome: clinical evaluation was performed by using a previously reported modified skin score, the MSS, which divides the whole body into 7 regions: head and neck, trunk, arms, hands, fingers, legs, and feet. The degree of thickness is assessed on a 0 to 3 scale (0, normal skin; 1, slightly palpable thickened skin; 2, decreased ability to move skin; 3, skin that is unable to be pinched or moved). In addition, involvement of each area is assessed (0: no involvement, 1: less than 33% involvement, 2: between 33% and 67% involvement, 3: more than 67% involvement). The sum of both thickness and affected area is the MSS, with a score of 0 for skin not affected and 42 representing extreme involvement as the maximum score. Secondary outcomes: assessment of the participants' estimate of tightness and itching on a visual analogue scale (VAS) from 0 to 10, 0 representing the absence of symptoms and 10 maximal tightness or itch, and ultrasound measurements with a digital 20 MHz ultrasound scanner to measure both structure and thickness of the skin. Authors also performed skin biopsies to assess skin involvement by a histologic score. Assessments: clinical evaluation at baseline, after therapy and at follow‐up, VAS before and after therapy, ultrasound measurements before and after therapy (on the same skin site), skin biopsies before and after phototherapy.
Notes	Intervention product details: LD UVA1 treatment was performed in a Sellas WL 20.000 bed (System Dr Sellmeier, Gevelsberg, Germany) and LD UVA1 measurements were performed with UV‐Meter (Waldmann, Villingen‐Schwenningen, Germany). MD UVA1 irradiation equipment consisted of a Photomed CL 300000 liquid (Photomed, Hamburg, Germany) and MD UVA1 measurements were performed with a calibrated photometer equipped with an MP‐136U photo detector (Photomed). NB UVB phototherapy was performed using the CosmedicoGP‐42 (Cosmedico Medizintechnik GmbH, Villingen‐Schwenningen, Germany) cabin fitted with Arimed 311 (Cosmedico Medizintechnik GmbH) fluorescent lamps. Digital 20‐MHz ultrasound scanner were performed using DUB 20 (Taberna pro medicum, Lüneburg, Germany) with a 8 mm usable depth of signal penetration.. Trial registration: authors did not register a protocol for this study. Ethics committee approval: local ethics review board. Funding sources: authors declared no funding sources. Declarations of interest: authors declared no conflict of interest.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Randomised assignment of the 3 phototherapeutic arms was performed by asking the patients to throw dice without knowing the underlying allocation criteria (numbers 1 and 2 = LD UVA1; 3 and 4 = MD UVA1; 5 and 6 = NB UVB)". Comment: the method used to generate the random sequence was adequate to produce comparable groups.
Allocation concealment (selection bias)	Low risk	Participants and investigators enrolling participants could not foresee assignment (sequence generation process: throwing dice).
Blinding of participants and personnel (performance bias) Subjective outcomes	High risk	Quote: "Lack of a double‐blinded setting. The latter is difficult to perform in photo dermatologic studies because irradiation time, UV cabin and equipment, and to a certain degree tanning response vary in different phototherapies"; Comment: participants and personnel had knowledge of the treatment. The outcome is likely to be influenced by lack of blinding.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Quote: "Image analysis of the ultrasound measurements was performed by an investigator who was blinded to any treatment details". Comment: only the ultrasound assessor was blinded from knowledge of which intervention a participant received. Assessors of the skin score and investigators who guided the participants in the VAS evaluation were unblinded. Thus, the primary outcome measurement of interest is likely to be influenced by lack of blinding.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Quote: "Two patients discontinued phototherapy before finishing the treatment protocol because of reasons independent to the trial. These patients were excluded from further statistical evaluation, and 62 patients were included in the ITT analysis". Comment: authors have performed 'as treated' analysis; however, the dropout rate probably does not represent serious threats to validity of the results as the study included 64 participants.
Selective reporting (reporting bias)	High risk	Authors did not report the length of the follow‐up after treatment, but responded to our contact and provided these data. However, authors reported only mean value for VAS results, without standard deviation, and did not provide us these data.
Other bias	Unclear risk	The clinical tool used (MSS) is validated for SSc, and is inappropriate for the measurement of morphea skin involvement, which could affect the result.