PMID- 34313812 OWN - NLM STAT- MEDLINE DCOM- 20211207 LR - 20240405 IS - 1437-160X (Electronic) IS - 0172-8172 (Print) IS - 0172-8172 (Linking) VI - 41 IP - 10 DP - 2021 Oct TI - Tofacitinib in the treatment of skin and musculoskeletal involvement in patients with systemic sclerosis, evaluated by ultrasound. PG - 1743-1753 LID - 10.1007/s00296-021-04956-7 [doi] AB - Systemic sclerosis (SSc) is a rare autoimmune connective tissue disease characterized by fibrosis of the skin and internal organs, autoimmunity-driven damage and vasculopathy. The current approved disease-modifying treatments have limited efficacy, and treatment is guided toward alleviating organ complications. Thus, there is an unmet need for discovering new effective treatment options. There is recent evidence that the JAK/STAT signaling pathway is markedly activated in SSc patients. To assess the efficacy and safety of tofacitinib (TOF) on skin and musculoskeletal involvement as compared to methotrexate (MTX) in systemic sclerosis (SSc). In this 52-week pilot study, 66 patients with SSc were enrolled: 33 patients received 5 mg of oral TOF twice a day; 33 received 10 mg of MTX weekly. The proportion of dcSSc and lcSSc patients was similar (dcSSc: 42% TOF group and 36% MTX group; lcSSc: 58% TOF group and 64% MTX group). The primary outcome was the change in the modified Rodnan skin score (mRSS). Secondary outcomes included ultrasound (US) skin thickness and musculoskeletal involvement (US10SSc score). Digital ulcers (DUs) and adverse events (AEs) were documented through the treatment. Both groups had similar characteristics and medians on the outcome measures at baseline. At week 52, the TOF median mRSS was significantly lower than the MTX (p < 0.001) with a mean reduction of 13 points versus MTX 2.57. The mean percent improvement in the TOF group was 44% higher than in the MTX group. TOF median US skin thickness was significantly lower than MTX (p < 0.001), with a mean reduction of 0.31 mm versus 0.075 mm in the MTX group. The US10SSc median score was significantly lower in the TOF group (p = 0.002); mean reduction of 10.21 versus 5.27 in the MTX group. Healing of DUs with no new occurrences was observed in the TOF group. There was no significant difference between the groups in the number of AEs from baseline to week 52. TOF showed greater efficacy than MTX in reducing mRSS, skin thickness and musculoskeletal involvement in SSc and a satisfactory safety profile. CI - (c) 2021. The Author(s). FAU - Karalilova, Rositsa Valerieva AU - Karalilova RV AUID- ORCID: 0000-0001-8030-0529 AD - Department of Internal Diseases, Medical University of Plovdiv, Plovdiv, Bulgaria. karalilova@hotmail.com. AD - Rheumatology Clinic, University Hospital "Kaspela", Plovdiv, Bulgaria. karalilova@hotmail.com. FAU - Batalov, Zguro Anastasov AU - Batalov ZA AUID- ORCID: 0000-0003-1233-5775 AD - Department of Internal Diseases, Medical University of Plovdiv, Plovdiv, Bulgaria. AD - Rheumatology Clinic, University Hospital "Kaspela", Plovdiv, Bulgaria. FAU - Sapundzhieva, Tanya Lyubomirova AU - Sapundzhieva TL AUID- ORCID: 0000-0002-2061-6473 AD - Department of Internal Diseases, Medical University of Plovdiv, Plovdiv, Bulgaria. AD - Rheumatology Clinic, University Hospital "Kaspela", Plovdiv, Bulgaria. FAU - Matucci-Cerinic, Marco AU - Matucci-Cerinic M AUID- ORCID: 0000-0002-9324-3161 AD - Department of Experimental and Clinical Medicine, University of Florence, Rheumatology Section, Florence, Italy. FAU - Batalov, Anastas Zgurov AU - Batalov AZ AUID- ORCID: 0000-0001-8857-0574 AD - Department of Internal Diseases, Medical University of Plovdiv, Plovdiv, Bulgaria. AD - Rheumatology Clinic, University Hospital "Kaspela", Plovdiv, Bulgaria. LA - eng PT - Journal Article PT - Randomized Controlled Trial DEP - 20210727 PL - Germany TA - Rheumatol Int JT - Rheumatology international JID - 8206885 RN - 0 (Immunosuppressive Agents) RN - 0 (Piperidines) RN - 0 (Protein Kinase Inhibitors) RN - 0 (Pyrimidines) RN - 87LA6FU830 (tofacitinib) RN - YL5FZ2Y5U1 (Methotrexate) SB - IM MH - Adult MH - Female MH - Humans MH - Immunosuppressive Agents/administration & dosage/adverse effects MH - Male MH - Methotrexate/administration & dosage/adverse effects MH - Middle Aged MH - Pilot Projects MH - Piperidines/*administration & dosage/adverse effects MH - Protein Kinase Inhibitors/*administration & dosage/adverse effects MH - Pyrimidines/*administration & dosage/adverse effects MH - Scleroderma, Systemic/complications/diagnostic imaging/*drug therapy MH - Severity of Illness Index MH - Skin/diagnostic imaging/pathology MH - Skin Ulcer/*prevention & control MH - Ultrasonography PMC - PMC8390399 OTO - NOTNLM OT - JAK/STAT OT - Systemic sclerosis OT - Tofacitinib OT - Ultrasound COIS- RK reports personal fees from AbbVie, Roche, Novartis and UCB. TS reports personal fees from AbbVie, Novartis and UCB. AB reports personal fees from AbbVie, Roche, Sandoz, MSD, Novartis, Pfizer, UCB, Boehringer Ingelheim, Lilly and Janssen. EDAT- 2021/07/28 06:00 MHDA- 2021/12/15 06:00 PMCR- 2021/07/27 CRDT- 2021/07/27 12:28 PHST- 2021/06/22 00:00 [received] PHST- 2021/07/18 00:00 [accepted] PHST- 2021/07/28 06:00 [pubmed] PHST- 2021/12/15 06:00 [medline] PHST- 2021/07/27 12:28 [entrez] PHST- 2021/07/27 00:00 [pmc-release] AID - 10.1007/s00296-021-04956-7 [pii] AID - 4956 [pii] AID - 10.1007/s00296-021-04956-7 [doi] PST - ppublish SO - Rheumatol Int. 2021 Oct;41(10):1743-1753. doi: 10.1007/s00296-021-04956-7. Epub 2021 Jul 27.