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Efficacy of Raynaud’s phenomenon and digital ulcer pharmacological treatment in systemic sclerosis patients: a systematic literature review

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Abstract

To evaluate the efficacy of current treatments for the Raynaud phenomenon (RP) in patients with systemic sclerosis (SSc), a systematic literature search was performed using Medline, EMBASE, and Cochrane Central Register of Controlled Trials (from 1961 to October 2011). We included meta-analyses, systematic reviews, clinical trials, and high-quality cohort studies published in English or Spanish. Patient populations had to include adults diagnosed with limited cutaneous or diffuse SSc who had associated RP and/or digital ulcers under pharmacological treatment. Efficacy of treatments was evaluated based on: number of RP episodes, RP severity, episode-free time, ulcer improvement/healing, and appearance of new ulcers. We used the Jadad scale of methodological quality to evaluate the quality of randomized clinical trials, and the 2009 Oxford Centre for Evidence-Based Medicine classification for other studies. Of a total of 1617 studies identified, only 27 fulfilled inclusion criteria. Drugs received the following grade recommendations: Grade A for nifedipine, nicardipine, quinapril, IV iloprost, bosentan, tadalafil, and MQx-503; Grade B for beraprost, cicaprost, DMSO, cyclofenil, and atorvastatin; and Grade C for misoprostol, prazosin, OPC-2826, enalapril, sildenafil, antioxidant, and stanazolol. Calcium channel blockers, prostanoids, tadalafil, and bosentan received the highest recommendation level for their effectiveness. However, most systematic reviews reviewed just a handful of studies with small sample sizes and short follow-ups. Our review shows that the existing evidence on the efficacy of RP treatment in SSc patients is inconclusive which calls for further research, especially in the form of prospective studies of high quality with long-term follow-ups.

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Acknowledgments

We thank Hosanna Soler Vila, PhD., for her contribution to this manuscript as medical writer. This work was funded by the Spanish Rheumatology Foundation through a non-restricted grant by ROCHE.

Conflict of interest

Dr. García de la Peña Lefebvre has no conflict of interest. Dr. Nishishinya has no conflict of interest. Dr. Pereda has no conflict of interest. Dr. Loza reports grants from Roche, Abbvie, BMS, Pfizer, Tigenix, MSD and Novartis. Dr. Sifuentes Giraldo has no conflict of interest. Dr. Román Ivorra has been speaker for Roche, Pfizer and BMS, advisory Group member: for Actelion, and clinical researcher for Abbvie, MSD and UCB. Dr. Carreira has no conflict of interest. Dr. Rúa-Figueroa has no conflict of interest. Dr. Pego-Reigosa was supported by BIOCAPS from the European Union 7th Framework Programme/REGPOT-2012-2013.1 (grant number 316265). Dr. Muñoz-Fernández has no conflict of interest.

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Authors and Affiliations

  1. Servicio de Reumatología, Hospitales Universitarios Grupo Madrid (Madrid, Montepríncipe, Sanchinarro y Torrelodones), c/Oña nº10, 28050, Madrid, Spain

    Paloma García de la Peña Lefebvre MD, PhD & Walter Alberto Sifuentes Giraldo MD

  2. Instituto Traumatológico, Hospital Quirón Barcelona, Barcelona, Spain

    María Betina Nishishinya MD

  3. Servicio de Reumatología, Clínica Mediterráneo, Almería, Spain

    Claudia Alejandra Pereda MD

  4. Instituto de Salud Musculoesquelética, Madrid, Spain

    Estíbaliz Loza MD

  5. Servicio de Reumatología, Hospital Universitario La Fe, Valencia, Spain

    José Andrés Román Ivorra MD

  6. Servicio de Reumatología, Hospital Universitario 12 de Octubre, Madrid, Spain

    Patricia Carreira MD

  7. Servicio de Reumatología, Hospital Universitario de Gran Canaria Doctor Negrín, Grand Canary, Spain

    Iñigo Rúa-Figueroa MD

  8. IRIDIS Group, Instituto de Investigación Biomédica (IBI), SERGAS, Xerencia de Xestión Integrada de Vigo, Pontevedra, Ourense, Spain

    Jose María Pego-Reigosa MD

  9. Sección de Reumatología, Hospital Universitario Infanta Sofía, San Sebastián de los Reyes, Madrid, Spain

    Santiago Muñoz-Fernández MD

  10. CEU Universidad San Pablo, Madrid, Spain

    Paloma García de la Peña Lefebvre MD, PhD

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  1. Paloma García de la Peña Lefebvre MD, PhD
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  2. María Betina Nishishinya MD
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Correspondence to Paloma García de la Peña Lefebvre MD, PhD.

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García de la Peña Lefebvre, P., Nishishinya, M.B., Pereda, C.A. et al. Efficacy of Raynaud’s phenomenon and digital ulcer pharmacological treatment in systemic sclerosis patients: a systematic literature review. Rheumatol Int 35, 1447–1459 (2015). https://doi.org/10.1007/s00296-015-3241-1

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  • DOI: https://doi.org/10.1007/s00296-015-3241-1

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