Use of sulfasalazine for psoriasis: An evidence-based review

To the Editor: Psoriasis is a chronic T-helper (Th)-1/Th-17 mediated inflammatory disease which often requires systemic therapy for skin clearance.1Menter A. Gelfand J.M. Connor C. et al.Joint American Academy of Dermatology-National Psoriasis Foundation guidelines of care for the management of psoriasis with systemic nonbiologic therapies.J Am Acad Dermatol. 2020; 82: 1445-1486https://doi.org/10.1016/j.jaad.2020.02.044Abstract Full Text Full Text PDF PubMed Scopus (184) Google Scholar,2Kagami S. Rizzo H.L. Lee J.J. Koguchi Y. Blauvelt A. Circulating Th17, Th22, and Th1 cells are increased in psoriasis.J Invest Dermatol. 2010; 130: 1373-1383https://doi.org/10.1038/jid.2009.399Abstract Full Text Full Text PDF PubMed Scopus (538) Google Scholar Sulfasalazine is an antiinflammatory medication comprised of sulphapyridine and 5-aminosalicylic acid and is used in many immune-mediated diseases.3Ogdie A. Coates L.C. Gladman D.D. Treatment guidelines in psoriatic arthritis.Rheumatology (Oxford). 2020; 59: i37-i46https://doi.org/10.1093/rheumatology/kez383Crossref PubMed Google Scholar,4Kang B.Y. Chung S.W. Im S.Y. Choe Y.K. Kim T.S. Sulfasalazine prevents T-helper 1 immune response by suppressing interleukin-12 production in macrophages.Immunology. 1999; 98: 98-103https://doi.org/10.1046/j.1365-2567.1999.00849.xCrossref PubMed Scopus (30) Google Scholar Despite having a favorable efficacy and safety profile demonstrated in small randomized trials, it is currently off-label for treatment of psoriatic arthritis and plaque psoriasis in North America.1Menter A. Gelfand J.M. Connor C. et al.Joint American Academy of Dermatology-National Psoriasis Foundation guidelines of care for the management of psoriasis with systemic nonbiologic therapies.J Am Acad Dermatol. 2020; 82: 1445-1486https://doi.org/10.1016/j.jaad.2020.02.044Abstract Full Text Full Text PDF PubMed Scopus (184) Google Scholar,3Ogdie A. Coates L.C. Gladman D.D. Treatment guidelines in psoriatic arthritis.Rheumatology (Oxford). 2020; 59: i37-i46https://doi.org/10.1093/rheumatology/kez383Crossref PubMed Google Scholar We performed a systematic review to assess outcomes of sulfasalazine for cutaneous psoriasis. We followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to search Embase and MEDLINE databases using several keywords (Supplementary Table I, available via Mendeley at https://doi.org/10.17632/34d9fjjng8.1). Quality of evidence was assessed using Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence. Original articles written in English reflecting an observational or experimental design were included. After independent screening by 2 reviewers, 10 articles encompassing 246 patients were included (Fig 1; Supplementary Table II, available via Mendeley at https://doi.org/10.17632/34d9fjjng8.1). The mean age was 24.1 years (range: 16-74 years) with sex reported in 176 (71.5%) instances (male: 72.7%, 128/176; female: 27.3%, 48/176). Comorbid psoriatic arthritis was present in 187/246 (76%) cases. Refractory disease to non-sulfasalazine systemic therapy was noted in 45.9% (113/246) of patients. The mean treatment duration was 18.4 weeks (range: 1.6-36 weeks). The most common daily dose of sulfasalazine was 2 g (82.5%, 203/246) (range: 1.5 g-4 g). Concomitant medications were used in 12.6% (31/246) of patients with frequent use of nonsteroidal antiinflammatory drugs (51.6%, 16/31) (Supplementary Table II, available via Mendeley at https://doi.org/10.17632/34d9fjjng8.1). In 8.9% (22/246) of patients, there was a reported complete clearance, and partial resolution was seen in 44.7% (110/246) of cases. No improvement was documented in 46.3% (114/246) of instances (Table I). In 49/246 cases where Psoriasis Area and Severity Index (PASI) was reported, sulfasalazine use led to a mean improvement of 48.4% (range: 47%-54.7%) within 18.4 weeks, including 5/49 (10.2%) and 2/49 (4.1%) patients achieving PASI-50 and PASI-75 respectively. In 158/246 cases where body surface area was reported, a reduction of 18.5% (range: 9.3%-66.7%) was seen. There were 87/264 (35.4%) treatment-emergent adverse events reported, commonly reflecting gastrointestinal intolerance (26.4%, 23/246) and nausea (17.2%, 15/246). In total, there were 40/246 (16.3%) discontinuations with 5/264 (1.9%) severe adverse events (Supplementary Table II, available via Mendeley at https://doi.org/10.17632/34d9fjjng8.1).Table ISummary of sulfasalazine outcomes for psoriasisStudy design (n/N, %) Randomized controlled trial5/10 (50%) Case report3/10 (30%) Prospective cohort study2/10 (20%)PASI PASI: mean (reported cases)−48.4% (49/246) PASI: range−47% to −54.7% PASI-50 responders (n/N, %)5/49 (10.2%) PASI-75 responders (n/N, %)2/49 (4.1%)BSA BSA: mean (reported cases)−18.5% (158/246) BSA: range−9.3% to −66.7%Treatment outcome CC (n/N, %)22/246 (8.9%)Mean treatment duration for CC (reported cases) (wk)16.3 (22/22)Mean follow-up period for CC (reported cases) (mo)6.1 (22/22) PR (n/N, %)110/246 (44.7%)Mean treatment duration for PR (reported cases) (wk)26.4 (110/110)Mean follow-up period for PR (reported cases) (mo)30.2 (110/110) NIM (n/N, %)114/246 (46.3%)Mean treatment duration for NIM (reported cases) (wk)29 (114/114)Mean follow-up period for NIM (reported cases) (mo)30.5 (114/114)Treatment characteristics Treatment duration (wk): mean18.4 Treatment duration (wk): range1.6 to 36 Follow-up period (mo): mean27.4 Follow-up period (mo): range0.25 to 168 Recurrence rate (n/N, %)8/132 (6.1%)Adverse events (n/N, %) Gastrointestinal intolerance23/246 (9.3%) Nausea15/246 (6.1%) Unspecified cutaneous eruption9/246 (3.7%) Neurological7/246 (2.8%) Fatigue6/246 (2.4%) Increased liver enzymes6/246 (2.4%) Heartburn3/246 (1.2%) Loss of taste2/246 (0.8%) Photosensitive eruption2/246 (0.8%) Purpura2/246 (0.8%) Hypertension1/246 (0.4%) Erythrodermic eruption∗Severe adverse events.1/246 (0.4%) Fever1/246 (0.4%) Impaired renal function∗Severe adverse events.1/246 (0.4%) Leukopenia1/246 (0.4%) Lymphadenopathy1/246 (0.4%) Macular eruption1/246 (0.4%) Nocturia1/246 (0.4%) Systemic fever, rash, and leukopenia∗Severe adverse events.1/246 (0.4%) Thrombocytopenia∗Severe adverse events.1/246 (0.4%) Toxic epidermal necrolysis∗Severe adverse events.1/246 (0.4%)BSA, Body surface area; CC, complete clearance; NIM, no improvement; PASI, Psoriasis Area and Severity Index; PR, partial resolution.∗ Severe adverse events. Open table in a new tab BSA, Body surface area; CC, complete clearance; NIM, no improvement; PASI, Psoriasis Area and Severity Index; PR, partial resolution. While the mechanism of action of sulfasalazine remains unclear, studies have demonstrated its inhibition of nuclear factor-κB activation in dendritic cells as well as Th1-related cytokines.4Kang B.Y. Chung S.W. Im S.Y. Choe Y.K. Kim T.S. Sulfasalazine prevents T-helper 1 immune response by suppressing interleukin-12 production in macrophages.Immunology. 1999; 98: 98-103https://doi.org/10.1046/j.1365-2567.1999.00849.xCrossref PubMed Scopus (30) Google Scholar,5Matasić R. Dietz A.B. Vuk-Pavlović S. Maturation of human dendritic cells as sulfasalazine target.Croat Med J. 2001; 42: 440-445PubMed Google Scholar Notably, we found 53.6% (132/246) of patients in this review improved or cleared on sulfasalazine, with few serious adverse events. Currently, sulfasalazine is outlined as an option for first-line conventional disease-modifying antirheumatic drug therapy in peripheral psoriatic arthritis.3Ogdie A. Coates L.C. Gladman D.D. Treatment guidelines in psoriatic arthritis.Rheumatology (Oxford). 2020; 59: i37-i46https://doi.org/10.1093/rheumatology/kez383Crossref PubMed Google Scholar Recent joint American Academy of Dermatology-National Psoriasis Foundation psoriasis guidelines do not provide a recommendation on sulfasalazine use. Study limitations include a small sample size of reported PASI data, incomplete follow-up data, and publication bias. While available efficacy findings are modest in comparison to other available psoriasis drugs, this review demonstrates sulfasalazine may provide an accessible low-cost option for a subset of psoriasis patients that have contraindications to other systemic agents or are refractory to first-line systemic immunosuppressives and biologics.1Menter A. Gelfand J.M. Connor C. et al.Joint American Academy of Dermatology-National Psoriasis Foundation guidelines of care for the management of psoriasis with systemic nonbiologic therapies.J Am Acad Dermatol. 2020; 82: 1445-1486https://doi.org/10.1016/j.jaad.2020.02.044Abstract Full Text Full Text PDF PubMed Scopus (184) Google Scholar Prospective studies should be conducted in special populations. Dr Yeung has been an advisor, consultant, speaker, and/or investigator for AbbVie, Amgen, Anacor, Arcutis, Astellas, Bausche, Baxalta, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Centocor, Coherus, Dermira, Forward, Fresenius Kabi, Galderma, Incyte, Janssen, LEO Pharma, Medimmune, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi Genzyme, Sun Pharma, Takeda, UCB, and Xenon. Authors Sood, Bagit, Drs Maliyar, Sachdeva, and Croitoru have no conflicts of interest to declare.

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