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Original Research: Diffuse Lung Disease |

A Randomized, Investigator-Masked, Double-Blind, Placebo-Controlled Trial on Thalidomide in Severe Cutaneous SarcoidosisThalidomide in Severe Cutaneous Sarcoidosis FREE TO VIEW

Catherine Droitcourt, MD; Michel Rybojad, MD; Raphaël Porcher, PhD; Caroline Juillard, MD; Anne Cosnes, MD; Pascal Joly, MD, PhD; Jean-Philippe Lacour, MD, PhD; Michel D’Incan, MD, PhD; Nicolas Dupin, MD, PhD; Bruno Sassolas, MD; Laurent Misery, MD, PhD; Jacqueline Chevrant-Breton, MD; Bénédicte Lebrun-Vignes, MD; Kristell Desseaux, MSc; Dominique Valeyre, MD, PhD; Jean Revuz, MD; Abdellatif Tazi, MD, PhD; Olivier Chosidow, MD, PhD; Alain Dupuy, MD, PhD
Author and Funding Information

From the Department of Dermatology (Drs Droitcourt, Dupuy, and Chevrant-Breton), CHU Rennes; Université de Rennes 1 (Drs Droitcourt, Dupuy, and Chevrant-Breton), and Pharmacoepidemiology Unit (Drs Droitcourt and Dupuy), Inserm CIC 1414, Rennes; the Department of Dermatology (Drs Rybojad and Juillard), the Department of Biostatistics and Medical Informatics (Dr Porcher and Ms Desseaux), and the Department of Pneumology (Dr Tazi), Hôpital Saint-Louis, AP-HP, Paris; Université de Paris Diderot-Sorbonne Paris Cité (Drs Porcher and Tazi and Ms Desseaux), Paris; Inserm U717 (Dr Porcher and Ms Desseaux), Paris; the Department of Dermatology (Dr Dupin), Hôpital Cochin, AP-HP, Paris; Université René Descartes (Dr Dupin), Paris; Pharmacovigilance Center (Dr Lebrun-Vignes), Groupe Hospitalier Pitié-Salpêtrière - Charles Foix, AP-HP, Paris; the Department of Pneumology (Dr Valeyre), Hôpital Avicenne, AP-HP, Bobigny; Université Paris-Nord (Dr Valeyre) Bobigny; 11 chaussée de la Muette (Dr Revuz), Paris; Clinique Dermatologique (Dr Joly), CHU Rouen, Rouen; Inserm U905, Institute for Research and Innovation in Biomedicine (IRIB) (Dr Joly), Université de Rouen, Rouen; the Department of Dermatology (Dr Lacour), Hôpital Archet-2, CHU Nice, Nice; Université de Nice (Dr Lacour), Sophia Antipolis, Nice; the Department of Dermatology (Dr D’Incan), CHU Estaing, and Université d’Auvergne (Dr D’Incan) Clermont-Ferrand; the Department of Dermatology (Drs Sassolas and Misery), CHRU Brest, Brest; UFR Medicine (Dr Misery), Université de Brest, Brest; the Department of Dermatology (Drs Cosnes and Chosidow), Hôpital Henri-Mondor, AP-HP, Créteil; UPEC Université de Paris Est-Créteil Val-de-Marne (Dr Chosidow), Créteil; and French satellite of the Cochrane Skin Group and Centre d’Investigation Clinique 006-Inserm (Dr Chosidow), Créteil, France.

CORRESPONDENCE TO: Alain Dupuy, MD, PhD, Department of Dermatology, Pontchaillou Hospital, 2 rue Henri le Guilloux, 35000 Rennes, France; e-mail: alain.dupuy@chu-rennes.fr


Dr Sassolas is currently at Cavala Blanche Hospital (Brest, France).

FUNDING/SUPPORT: Assistance-Publique Hôpitaux-de-Paris provided funding for this trial [Grant CRC03156]. Laphal Industries provided thalidomide and placebo.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2014;146(4):1046-1054. doi:10.1378/chest.14-0015
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BACKGROUND:  Thalidomide use in cutaneous sarcoidosis is based on data from small case series or case reports. The objective of this study was to evaluate the efficacy and safety of thalidomide in severe cutaneous sarcoidosis.

METHODS:  This study consisted of a randomized, double-bind, parallel, placebo-controlled, investigator-masked, multicenter trial lasting 3 months and an open-label study from month 3 to month 6. Adults with a clinical and histologic diagnosis of cutaneous sarcoidosis were included in nine hospital centers in France. Patients were randomized 1:1 to oral thalidomide (100 mg once daily) or to a matching oral placebo for 3 months. In the course of an open-label follow-up from month 3 to month 6, all patients received thalidomide, 100 mg to 200 mg daily. The proportions of patients with a partial or complete cutaneous response at month 3, based on at least a 50% improvement in three target lesions scored for area and infiltration, were compared across randomization groups.

RESULTS:  The intent-to-treat population included 39 patients. None of them had a complete cutaneous response. Four out of 20 patients in the thalidomide group (20%) vs four out of 19 patients in the placebo group (21%) had a partial cutaneous response at month 3 (difference in proportion of −1% [95% CI, −26% to +24%] for thalidomide vs placebo, P = 1.0). Eight patients with side effects were recorded in the thalidomide group vs three in the placebo group. We observed a large number of adverse event-related discontinuations in patients taking thalidomide in the first 3 months (four patients with thalidomide, zero with placebo) and in the 3 following months (five patients).

CONCLUSIONS:  At a dose of 100 mg daily for 3 months, our results do not encourage thalidomide use in cutaneous sarcoidosis.

TRIAL REGISTRY:  ClinicalTrials.gov; No.: NCT0030552; URL: www.clinicaltrials.gov

Figures in this Article

Sarcoidosis is a multisystemic disorder characterized by noncaseating granulomas occurring in several organs. Lung, lymph nodes, skin, and eyes are the most commonly involved sites. Skin is involved in 25%-35% of patients.1 Cutaneous lesions include a large range of clinical manifestations, from limited to extensive lesions, and even limited lesions can impact on quality of life if located on the face.1,2

For extensive cutaneous lesions, antimalarials, cyclines, systemic corticosteroids, immunosuppressants (methotrexate, azathioprine, and others), and, more recently, tumor necrosis factor (TNF)-α inhibitors can be used.3 Because, to our knowledge, only one controlled study4 involving these agents is available, their use and indications are based on clinical experience and vary from center to center. An antimycobacterial antibiotics-based regimen has also been proposed recently.5

The pathophysiology of sarcoidosis is still unclear, but it is usually classified as a T-helper (Th) type 1 response, related to an as yet undefined antigen. Thalidomide could inhibit TNF-α production by monocytes and alveolar macrophages,6,7 increase the degradation of TNF-α mRNA,8 and selectively suppress the nuclear factor κ light chain enhancer of activated B cells induced by TNF-α.9 Thalidomide induces and increases IL-4 and IL-5 production and decreases interferon-γ production, suggesting that thalidomide could support a switch from the Th1 response observed in sarcoidosis to a Th2 response.10 Consequently, thalidomide has been proposed as a treatment of severe cutaneous sarcoidosis, but its efficacy has been hypothesized only in case reports and case series.1121 We, therefore, conducted a parallel-group placebo-controlled trial in patients with sarcoidosis and severe cutaneous lesions.

Trial Design

We performed a randomized, double-bind, placebo-controlled, multicentre trial to assess thalidomide efficacy and safety in patients with severe cutaneous sarcoidosis. Patients from nine hospitals in France were enrolled from January 2005 to January 2007.

Treatments were allocated by minimization, centralized in the data center, and stratified on center and on cotreatment with oral corticosteroids in a 1:1 allocation ratio, using blocks of random size. The data center provided the randomization numbers to the manufacturer, and the prenumbered treatment was then shipped to the hospital pharmacies. A subcontracted company was in charge of labeling and packaging unrelated to the content.

The main outcome was assessed and compared between randomized groups at month 3. A 3-month open-label follow-up was then implemented from month 3 to month 6. The initial treatment allocation remained blinded until month 6 (Fig 1).

Patients

This study was approved by our local ethics committee (Comité Consultatif de Protection des Personnes dans la Recherche Biomédicale, Assistance Publique- Hôpitaux de Paris, Saint-Louis, Paris, France) under approval reference CPP 2004/44, September 30, 2004. Written informed consent was obtained from all patients at screening.

Inclusion Criteria:

Eligibility criteria included age ≥ 18 years; a diagnosis of sarcoidosis confirmed by histologic examination of a skin biopsy specimen; chronic (≥ 12 months) severe cutaneous sarcoidosis with either disfiguring or extensive skin involvement, with altered quality of life (as assessed by the investigators; see later discussion); a daily dose of systemic corticosteroids of no more than 15 mg of prednisone or prednisolone, the same for at least 2 months before inclusion; and previous ineffective treatments, including hydroxychloroquine, tetracyclines, or immunosuppressant drugs to have been discontinued for at least 1 month before inclusion.

Exclusion Criteria:

Exclusion criteria included suspicion of any other cutaneous granulomatous disease; a history of treatment with thalidomide; visceral involvement justifying a high dosage of systemic corticosteroids (> 15 mg per day) or other immunosuppressant drugs; peripheral neuropathy evaluated by clinical examination and electromyography; renal failure (glomerular filtration rate ≤ 50 mL/min using the Cockcroft formula); pregnancy or desire for pregnancy; a history of thromboembolic disease; or any other contraindication to thalidomide treatment.

Initial Evaluation and Follow-up:

A screening visit included the following: verification of inclusion and exclusion criteria, complete physical examination, ECG, blood count, biochemical screening, serum angiotensin-converting enzyme level, and electromyography. Oral and written consent for contraception were obtained for all nonmenopausal women. All women of childbearing age were started on a suitable estroprogestative contraceptive regimen 1 month before inclusion, which was maintained for 1 month after treatment discontinuation. Men were instructed to use barrier methods during the study and for 8 days after treatment discontinuation.

Baseline and monthly follow-up consisted of clinical assessment of cutaneous lesions, physical examination, recording of adverse events, skin-related quality-of-life assessment using the Skindex score,22 blood count, biochemical screening tests, and qualitative β-human chorionic gonadotropin blood test for all nonmenopausal women, performed monthly in the first 3 months and in the 3-month open-label follow-up. Electromyography was performed 3 months after stopping treatment or in the case of abnormality in neurologic examination.

Interventions

In the 3-month randomized period, one group received oral thalidomide (fixed dose of 100 mg once daily, [ie, two tablets of 50 mg]) and the other group received a matching oral placebo (once daily, two tablets). Thalidomide and placebo tablets were of identical appearance and taste.

Then, during the open-label follow-up study from month 3 to month 6, all patients received thalidomide at an initial dose of 100 mg once daily. The investigators increased the thalidomide dose on the basis of their own judgment of efficacy and tolerance, with increments of 50 mg monthly up to a maximum 200-mg daily dose (Fig 1). The treatment received during the randomized period (either placebo or thalidomide from month 0 to month 3) remained blinded until the end of the study. In this report, the randomized groups are labeled as “thalidomide-thalidomide” and “placebo-thalidomide” when referring to the second part of the study.

Outcomes
Main Efficacy Outcome:

The primary end point was the percentage of patients with complete or partial cutaneous response at month 3. The response was assessed by scoring three cutaneous lesions selected as targets as follows: in the case of facial involvement, one of the three lesions was to be on the face; the two other lesions were selected as the most representative. Each lesion was assessed for area (product of the larger diameter by its perpendicular diameter) and infiltration (0 = no infiltration, 1 = slight infiltration, 2 = moderate infiltration, 3 = marked infiltration, 4 = very marked infiltration). Two evaluators assessed the three target cutaneous lesions: the investigator responsible for the patient performed monthly assessments; in each center, an independent evaluator not involved in patient care, and blinded to treatment allocation and adverse events, assessed the target cutaneous lesions at month 0 and month 3. This independent evaluator’s assessment was used for the statistical analysis; if not available (n = 2 and n = 4 at month 3 in the thalidomide and placebo groups, respectively), the investigator’s assessment was used instead.

A patient was classified as a responder at month 3 if conditions a, b, and c were fulfilled: (a) reduction in the area of all three target cutaneous lesions by at least 50% from baseline, (b) reduction in the infiltration of all three target cutaneous lesions by at least 50% from baseline, and (c) no new lesion and no marked deterioration of nontarget lesions. Response was deemed complete if all the lesions had disappeared; if they had not disappeared, response was considered incomplete. Otherwise, patients were classified as nonresponders.

Secondary Efficacy Outcomes:

Secondary outcomes included investigator’s global assessment of skin lesions based on a Likert scale (deterioration, no change, uncertain, discordant change (some lesions improved, some deteriorated), improvement, very good improvement, or complete healing); patient assessment using the same scale; and Skindex quality-of-life score and thalidomide safety assessment (adverse effects).

Harmful Effects:

No preestablished list was implemented for harm-related outcomes except for signs related to neuropathy and electromyographic data. Intensity was scored as severe or nonsevere on the basis of the investigator’s assessment. Rules for treatment discontinuation were at the discretion of the investigator. Side effects were classified as benign, moderate, or severe.

Sample Size and Statistical Analysis

A sample of 20 patients per group was planned to yield a power of 80% to detect an absolute difference of 50% in complete or partial response rate between thalidomide and placebo, based on 20% estimated responders in the placebo group (two-sided 5% significance level) (ie, at least 70% of responders in the thalidomide group). The analysis was carried out according to the intent-to-treat (ITT) principle (ie, all patients randomized were analyzed in the arm to which they were allocated). In addition, an analysis of evaluated cases was presented as a secondary analysis. Patients who discontinued treatment before month 3 were assessed as planned at month 3 as far as possible, and in the case of missing data, their outcome was imputed as failure or the lowest physician or patient global assessment score. Missing Skindex scores were imputed as the baseline value. Efficacy outcomes and adverse effects were analyzed using the same methods. Binary variables were compared using Fisher exact tests. The 95% CIs for the differences in proportion were based on Wilson’s score. Ordered categorical variables such as physician and patient global assessments were compared using Wilcoxon rank sum tests. Skindex scores were compared using Student t tests with unequal variances, and covariance analysis was used to adjust for baseline Skindex scores. For the open-label follow-up study, only those cases that were evaluated are presented. All tests were two-sided at a .05 significance level. The analysis was conducted with SAS software (SAS Inc) and R 2.15.2 (R Foundation for Statistical Computing).

Funding

Assistance-Publique Hôpitaux-de-Paris provided funding and promoted the trial. Celgene Inc manufactured the thalidomide and placebo tablets.

Forty patients with cutaneous sarcoidosis participated in the study. One patient withdrew consent before randomization. Twenty patients were randomized in the thalidomide group and 19 in the placebo group (Fig 2). Thirty-five patients completed the study at month 3: 16 in the thalidomide group and 19 in the placebo group. One center included 21 patients (54%), and eight centers included one to three patients. Four patients dropped out because of side effects.

Baseline characteristics of the patients are listed in Table 1. Overall, demographics and disease characteristics were balanced between the groups.

Table Graphic Jump Location
TABLE 1 ]  Baseline Clinical Characteristics and Extracutaneous Assessment of Patients With Cutaneous Sarcoidosis

Data are presented as No. (%) or mean (range). NYHA = New York Heart Association.

Regarding the primary end point (ie, the three target skin lesions) at month 3, four out of 16 evaluated patients (20%) in the thalidomide group vs four out of 19 patients (21%) in the placebo group had a partial cutaneous response (Table 2). ITT analysis yielded a difference in proportion of −1% (95% CI, −26% to +24%) for thalidomide vs placebo (P = 1.0). No patient had a complete cutaneous response.

Table Graphic Jump Location
TABLE 2 ]  Cutaneous Response at Mo 3 (Primary and Secondary End Points)
a 

Adjusted on baseline Skindex score.

Results for the secondary end points are reported in Table 2. Among the evaluated cases, although five patients in the placebo group were classified under “deterioration” according to the semiquantitative estimate with the investigator’s global assessment scale vs zero patients of the 16 evaluated in the thalidomide group, no significant trend to a better global assessment was observed in the ITT and evaluated case analyses (P = .1). Assessment by patients yielded 10 patients in the thalidomide group experiencing “improvement,” “very good improvement,” or “complete healing” vs 11 patients in the placebo group for the same categories (P = .87 for the overall distribution between randomized groups). There was no significant difference in the improvement of quality of life at month 3 between the thalidomide and the placebo group (adjusted mean difference, −5.9; 95% CI, −15.0 to +3.2; P = .19).

The results of the open-label follow-up study are presented in Table 3. At month 6, 28 patients had completed the study, 14 in the thalidomide-thalidomide group and 14 in the placebo-thalidomide group. At month 6, 11 vs 10 patients were classified under “improvement” or “very good improvement” according to the investigator global assessment (in the thalidomide-thalidomide group and placebo-thalidomide group, respectively). Skindex scores were 56 (95% CI, 38.0-94.5) and 44 (95% CI, 32.0-68).

Table Graphic Jump Location
TABLE 3 ]  Cutaneous Response at Mo 6 (Primary and Secondary End Points)
a 

Adjusted on baseline Skindex score.

Because of some leeway in dose adaptation during the second period, some patients had their dose increased. Among the patients for whom information was available (number larger than the number evaluated), 11 (73%), three (20%), and one (7%) in the thalidomide-thalidomide group and 13 (81%), three (19%), and zero (0%) in the placebo-thalidomide group received a maximum dose of 100, 150, and 200 mg/d, respectively. No patient receiving 150 or 200 mg/d reported any adverse event during the open-label follow-up study.

Between month 0 and month 3, eight out of 20 patients in the thalidomide group and three out of 19 patients in the placebo group experienced adverse events. Between month 3 and month 6, three out of 16 patients in the thalidomide-thalidomide group and nine out of 14 patients in the placebo-thalidomide group experienced adverse events. Between month 0 and month 3, serious adverse events were recorded in three patients from the thalidomide group: one patient had drowsiness, abdominal pain, diarrhea, dizziness, and headache; one patient had skin rash, leg edema, cough, and fever; and one patient had dyspnea and dizziness. One serious adverse event was reported in the placebo group: one patient had sensitive neuropathy confirmed by electromyography. Between month 3 and month 6, serious adverse events were recorded in two patients in the thalidomide-thalidomide group (one patient had chest and elbow pain, and one patient had depression and peripheral facial paralysis) and in three patients in the placebo-thalidomide group (one patient had headache and dizziness, one patient had cerebral hemorrhage, and one patient had hypothyroidism).

In this randomized, placebo-controlled, double-blind trial in patients with cutaneous sarcoidosis, we observed similar, low response rates in patients receiving thalidomide and placebo at month 3 (20% vs 21%). We observed a large number of adverse event-related discontinuations in patients receiving thalidomide.

The rationale for assessing thalidomide efficacy in cutaneous sarcoidosis in a placebo-controlled study was based on encouraging results from case reports and case series.11,1621 At variance with these preliminary data, our study suggests that thalidomide has no major therapeutic effect in cutaneous sarcoidosis, and that the observed successes are no more frequent than the rate observed with placebo. We implemented an investigator-masked outcome evaluation by using an independent assessor not involved in patient care. Thus, we limited information bias in outcome assessment. However, because the independent assessment was lacking for six patients, the investigator assessment was used instead. Target lesion-based outcomes and outcomes based on global assessment of skin lesions yielded similar results.

Some limitations should be discussed. First, the 3-month duration of the placebo-controlled trial was a pragmatic choice based on clinical experience and may have been too short to observe a difference; a 6-month follow-up may have been more appropriate and has been chosen in other placebo-controlled randomized trials assessing thalidomide in noncutaneous sarcoidosis.2326 In cutaneous sarcoidosis, a noncontrolled study in 19 patients21 demonstrated a relatively low rate of success of 32%, close to ours, at month 3, based on Sarcoidosis Activity and Diffusion Index assessment. At month 6, however, a higher success rate of 67% was recorded. In our study, in the global assessment at month 6, we also observed higher success rates.

Second, in our study, the dose of thalidomide was limited to 100 mg/d in the first 3 months, whereas most other reports1921 used doses up to 200 mg/d, at least part of the time. Therefore, a suboptimal dose may partly account for our disappointing results.

Last, the power of our study should be discussed. We included 39 of the 40 patients planned, and the confidence interval for the difference in efficacy between groups excludes a 40% difference of patients in partial remission. Although our results make it possible to rule out any dramatic effect of thalidomide, the power of this study is limited, and a smaller difference between thalidomide and placebo cannot be excluded.

A general limitation in comparing study results in cutaneous sarcoidosis is the lack of uniform outcome criteria. Several scores have been proposed4,5,21,27 to assess severity in skin sarcoidosis, but few of them have gone through validation processes and none of them was available at the time the protocol was drafted. Photographs have limitations in skin sarcoidosis, because they do not enable infiltration assessment. Since this study was implemented, several instruments have been published,21,27,28 most of them based on combinations of similar items, some of them with validation studies.27,28 A limitation of this study is the absence of validation of our scores.

In our study, the placebo group had a response rate of 21% at month 3. In two other recent placebo-controlled trials in skin sarcoidosis, the success rates observed in the placebo groups were 0% and 20%, with limitations caused by the small number of patients and an attrition bias.4,5 In placebo-controlled trials targeting organs other than skin, the response rates in placebo groups ranged from 8% to 16%.23,25,26,29 Comparisons are hindered by both the difference in target organs and the definition of response rates. However, sarcoidosis should be considered as a disease in which spontaneous evolution or the placebo effect can lead to significant improvement over time. Placebo-controlled trials are, therefore, critical to assess treatment efficacy in this disease.

In the 6 months of our study, diverse adverse events were recorded, and a fair proportion of them led to treatment discontinuation. Peripheral neuropathy, a well-recognized side effect of thalidomide, was observed in only one patient, whereas other studies reported peripheral neuropathy in a much larger proportion of patients (seven of 19 patients in a 2-year follow-up prospective study21). The longer duration of treatment in Fazzi et al21 could account for this difference, although peripheral neuropathy is suspected to be linked more to daily dose than to duration of treatment.30

The results of this study do not encourage consideration of thalidomide as a mainstream treatment in skin sarcoidosis because of a lack of efficacy and issues of tolerance. The small sample size is a limitation of this trial, and larger controlled studies are needed to confirm our results. Our study underlines the usefulness of a placebo for validating new drugs in cutaneous sarcoidosis. The severity score improved in some patients under placebo, and this should be viewed as a note of caution for the evaluation of drugs in a before-and-after comparison without a control group.

Author contributions: A. D. had full access to all the data in the study and is the guarantor of the manuscript. A. D., M. R., R. P., O. C., J. R., and D. V. contributed to the planning of the study and the study design; R. P. and K. D. contributed to data analysis; A. D., M. R., C. D., R. P., O. C., J. R., D. V., and A. T. contributed to data interpretation; A. D., M. R., O. C., J. R., D. V., A. T., C. J., A. C., P. J., J.-P. L., M. D., N. D., B. S., L. M., J. C.-B., and B. L.-V. contributed to recruitment of study subjects; A. D., M. R., R. P., O. C., J. R., and D. V. contributed to obtaining the project funding; A. D. and C. D. contributed to the drafting of the initial manuscript; and A. D., M. R., C. D., R. P., O. C., J. R., D. V., A. T., C. J., A. C., P. J., J.-P. L., M. D., N. D., B. S., L. M., J. C.-B., B. L.-V., and K. D. contributed to commenting on and improving the first draft and approval of the final manuscript as submitted.

Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Role of sponsors: The sponsors had no role in the design of the study, the collection and analysis of the data, or in the preparation of the manuscript.

Other contributions: We thank Julie Tequi-Lebras for technical assistance and Angela Swaine-Verdier for editorial assistance.

ITT

intent to treat

Th

T helper

TNF

tumor necrosis factor

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Baltzan M, Mehta S, Kirkham TH, Cosio MG. Randomized trial of prolonged chloroquine therapy in advanced pulmonary sarcoidosis. Am J Respir Crit Care Med. 1999;160(1):192-197. [CrossRef] [PubMed]
 
du Bois RM, Greenhalgh PM, Southcott AM, Johnson NM, Harris TA. Randomized trial of inhaled fluticasone propionate in chronic stable pulmonary sarcoidosis: a pilot study. Eur Respir J. 1999;13(6):1345-1350. [CrossRef] [PubMed]
 
Alberts C, van der Mark TW, Jansen HM; Dutch Study Group on Pulmonary Sarcoidosis. Inhaled budesonide in pulmonary sarcoidosis: a double-blind, placebo-controlled study. Eur Respir J. 1995;8(5):682-688. [PubMed]
 
Baughman RP, Judson MA, Teirstein A, et al. Chronic facial sarcoidosis including lupus pernio: clinical description and proposed scoring systems. Am J Clin Dermatol. 2008;9(3):155-161. [CrossRef] [PubMed]
 
Rosenbach M, Yeung H, Chu EY, et al. Reliability and convergent validity of the cutaneous sarcoidosis activity and morphology instrument for assessing cutaneous sarcoidosis. JAMA Dermatol. 2013;149(5):550-556. [CrossRef] [PubMed]
 
Judson MA, Baughman RP, Costabel U, et al; Centocor T48 Sarcoidosis Investigators. Efficacy of infliximab in extrapulmonary sarcoidosis: results from a randomised trial. Eur Respir J. 2008;31(6):1189-1196. [CrossRef] [PubMed]
 
Bastuji-Garin S, Ochonisky S, Bouche P, et al; Thalidomide Neuropathy Study Group. Incidence and risk factors for thalidomide neuropathy: a prospective study of 135 dermatologic patients. J Invest Dermatol. 2002;119(5):1020-1026. [CrossRef] [PubMed]
 

Tables

Table Graphic Jump Location
TABLE 1 ]  Baseline Clinical Characteristics and Extracutaneous Assessment of Patients With Cutaneous Sarcoidosis

Data are presented as No. (%) or mean (range). NYHA = New York Heart Association.

Table Graphic Jump Location
TABLE 2 ]  Cutaneous Response at Mo 3 (Primary and Secondary End Points)
a 

Adjusted on baseline Skindex score.

Table Graphic Jump Location
TABLE 3 ]  Cutaneous Response at Mo 6 (Primary and Secondary End Points)
a 

Adjusted on baseline Skindex score.

References

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Fazzi P, Manni E, Cristofani R, et al. Thalidomide for improving cutaneous and pulmonary sarcoidosis in patients resistant or with contraindications to corticosteroids. Biomed Pharmacother. 2012;66(4):300-307. [CrossRef] [PubMed]
 
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Baughman RP, Lower EE, Bradley DA, Raymond LA, Kaufman A. Etanercept for refractory ocular sarcoidosis: results of a double-blind randomized trial. Chest. 2005;128(2):1062-67. [PubMed]
 
Baltzan M, Mehta S, Kirkham TH, Cosio MG. Randomized trial of prolonged chloroquine therapy in advanced pulmonary sarcoidosis. Am J Respir Crit Care Med. 1999;160(1):192-197. [CrossRef] [PubMed]
 
du Bois RM, Greenhalgh PM, Southcott AM, Johnson NM, Harris TA. Randomized trial of inhaled fluticasone propionate in chronic stable pulmonary sarcoidosis: a pilot study. Eur Respir J. 1999;13(6):1345-1350. [CrossRef] [PubMed]
 
Alberts C, van der Mark TW, Jansen HM; Dutch Study Group on Pulmonary Sarcoidosis. Inhaled budesonide in pulmonary sarcoidosis: a double-blind, placebo-controlled study. Eur Respir J. 1995;8(5):682-688. [PubMed]
 
Baughman RP, Judson MA, Teirstein A, et al. Chronic facial sarcoidosis including lupus pernio: clinical description and proposed scoring systems. Am J Clin Dermatol. 2008;9(3):155-161. [CrossRef] [PubMed]
 
Rosenbach M, Yeung H, Chu EY, et al. Reliability and convergent validity of the cutaneous sarcoidosis activity and morphology instrument for assessing cutaneous sarcoidosis. JAMA Dermatol. 2013;149(5):550-556. [CrossRef] [PubMed]
 
Judson MA, Baughman RP, Costabel U, et al; Centocor T48 Sarcoidosis Investigators. Efficacy of infliximab in extrapulmonary sarcoidosis: results from a randomised trial. Eur Respir J. 2008;31(6):1189-1196. [CrossRef] [PubMed]
 
Bastuji-Garin S, Ochonisky S, Bouche P, et al; Thalidomide Neuropathy Study Group. Incidence and risk factors for thalidomide neuropathy: a prospective study of 135 dermatologic patients. J Invest Dermatol. 2002;119(5):1020-1026. [CrossRef] [PubMed]
 
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