Psoriatic Arthritis

Key clinical point: Concomitant methotrexate had no effect on ustekimumab immunogenicity in patients with psoriatic arthritis (PsA), with the formation of antidrug antibody (ADA) not being associated with reductions in ustekinumab safety or efficacy.

Major finding: The prevalence of ADA at week 52 was not significantly different between the ustekinumab+methotrexate and ustekinumab+placebo groups, with disease activity, treatment response, dropout rates, effect of pretreatment with methotrexate, and safety outcomes not being significantly different in patients with vs without ADA (all P > .05).

Study details: This post hoc analysis of the MUST trial included 112 patients with active PsA who were naive to ustekimumab and were randomly assigned to receive ustekinumab with concomitant methotrexate or placebo.

Disclosures: This study was funded by Innovative Medicines Initiative 2 Joint Undertaking, which received support from the European Union’s Horizon 2020 Research and Innovation Program and others. F Behrens, M Koehm, and H Burkhardt declared receiving research grants from Janssen Cilag. The other authors reported no conflicts of interest.

Source: Poor SM et al. The role of antidrug antibodies in ustekinumab therapy and the impact of methotrexate. Rheumatology (Oxford). 2023 (Apr 20). Doi: 10.1093/rheumatology/kead177

Key clinical point: Concomitant methotrexate had no effect on ustekimumab immunogenicity in patients with psoriatic arthritis (PsA), with the formation of antidrug antibody (ADA) not being associated with reductions in ustekinumab safety or efficacy.

Major finding: The prevalence of ADA at week 52 was not significantly different between the ustekinumab+methotrexate and ustekinumab+placebo groups, with disease activity, treatment response, dropout rates, effect of pretreatment with methotrexate, and safety outcomes not being significantly different in patients with vs without ADA (all P > .05).

Study details: This post hoc analysis of the MUST trial included 112 patients with active PsA who were naive to ustekimumab and were randomly assigned to receive ustekinumab with concomitant methotrexate or placebo.

Disclosures: This study was funded by Innovative Medicines Initiative 2 Joint Undertaking, which received support from the European Union’s Horizon 2020 Research and Innovation Program and others. F Behrens, M Koehm, and H Burkhardt declared receiving research grants from Janssen Cilag. The other authors reported no conflicts of interest.

Source: Poor SM et al. The role of antidrug antibodies in ustekinumab therapy and the impact of methotrexate. Rheumatology (Oxford). 2023 (Apr 20). Doi: 10.1093/rheumatology/kead177

Key clinical point: Concomitant methotrexate had no effect on ustekimumab immunogenicity in patients with psoriatic arthritis (PsA), with the formation of antidrug antibody (ADA) not being associated with reductions in ustekinumab safety or efficacy.

Major finding: The prevalence of ADA at week 52 was not significantly different between the ustekinumab+methotrexate and ustekinumab+placebo groups, with disease activity, treatment response, dropout rates, effect of pretreatment with methotrexate, and safety outcomes not being significantly different in patients with vs without ADA (all P > .05).

Study details: This post hoc analysis of the MUST trial included 112 patients with active PsA who were naive to ustekimumab and were randomly assigned to receive ustekinumab with concomitant methotrexate or placebo.

Disclosures: This study was funded by Innovative Medicines Initiative 2 Joint Undertaking, which received support from the European Union’s Horizon 2020 Research and Innovation Program and others. F Behrens, M Koehm, and H Burkhardt declared receiving research grants from Janssen Cilag. The other authors reported no conflicts of interest.

Source: Poor SM et al. The role of antidrug antibodies in ustekinumab therapy and the impact of methotrexate. Rheumatology (Oxford). 2023 (Apr 20). Doi: 10.1093/rheumatology/kead177

Key clinical point: The entheseal fibrocartilage (EF) thickness assessed during power Doppler ultrasound evaluation was significantly different among patients with psoriatic arthritis (PsA) and control individuals and can be explored as an imaging biomarker for PsA.

Major finding: The median EF thickness was significantly greater in patients with PsA and athletes vs control individuals (0.035 and 0.036 vs 0.030 cm, respectively; P  =  .05 and P  =  .008, respectively), with the intra- and inter-reader reliability of the evaluation of EF thickness being excellent (intraclass correlation coefficient [ICC] 0.91) and good (ICC 0.80; both P < .001), respectively.

Study details: This cross-sectional study included patients with PsA (n = 30), athletes (n = 40), and control individuals (n = 20) who underwent power Doppler ultrasound evaluation during bilateral Achilles tendon insertions.

Disclosures: This study did not receive any external funding. The authors declared no conflicts of interest.

Source: Perrotta FM et al. Ultrasonographic evaluation of entheseal fibrocartilage in patients with psoriatic arthritis, athletes and healthy controls: A comparison study. Diagnostics (Basel). 2023;13(8):1446 (Apr 17). Doi: 10.3390/diagnostics13081446

Key clinical point: The entheseal fibrocartilage (EF) thickness assessed during power Doppler ultrasound evaluation was significantly different among patients with psoriatic arthritis (PsA) and control individuals and can be explored as an imaging biomarker for PsA.

Major finding: The median EF thickness was significantly greater in patients with PsA and athletes vs control individuals (0.035 and 0.036 vs 0.030 cm, respectively; P  =  .05 and P  =  .008, respectively), with the intra- and inter-reader reliability of the evaluation of EF thickness being excellent (intraclass correlation coefficient [ICC] 0.91) and good (ICC 0.80; both P < .001), respectively.

Study details: This cross-sectional study included patients with PsA (n = 30), athletes (n = 40), and control individuals (n = 20) who underwent power Doppler ultrasound evaluation during bilateral Achilles tendon insertions.

Disclosures: This study did not receive any external funding. The authors declared no conflicts of interest.

Source: Perrotta FM et al. Ultrasonographic evaluation of entheseal fibrocartilage in patients with psoriatic arthritis, athletes and healthy controls: A comparison study. Diagnostics (Basel). 2023;13(8):1446 (Apr 17). Doi: 10.3390/diagnostics13081446

Key clinical point: The entheseal fibrocartilage (EF) thickness assessed during power Doppler ultrasound evaluation was significantly different among patients with psoriatic arthritis (PsA) and control individuals and can be explored as an imaging biomarker for PsA.

Major finding: The median EF thickness was significantly greater in patients with PsA and athletes vs control individuals (0.035 and 0.036 vs 0.030 cm, respectively; P  =  .05 and P  =  .008, respectively), with the intra- and inter-reader reliability of the evaluation of EF thickness being excellent (intraclass correlation coefficient [ICC] 0.91) and good (ICC 0.80; both P < .001), respectively.

Study details: This cross-sectional study included patients with PsA (n = 30), athletes (n = 40), and control individuals (n = 20) who underwent power Doppler ultrasound evaluation during bilateral Achilles tendon insertions.

Disclosures: This study did not receive any external funding. The authors declared no conflicts of interest.

Source: Perrotta FM et al. Ultrasonographic evaluation of entheseal fibrocartilage in patients with psoriatic arthritis, athletes and healthy controls: A comparison study. Diagnostics (Basel). 2023;13(8):1446 (Apr 17). Doi: 10.3390/diagnostics13081446

Key clinical point: Compared with placebo, 15 mg upadacitinib led to a greater improvement in axial symptoms with a consistent safety profile in patients with psoriatic arthritis (PsA).

Major finding: The improvement in overall Bath Ankylosing Spondylitis Disease Activity Index score at week 24 was significantly higher with 15 mg upadacitinib vs placebo in both SELECT-PsA 1 (−3.12 vs −1.70; P < .0001) and SELECT PsA 2 (−2.06 vs −0.21; P < .0001) trials. Treatment-emergent adverse events were generally similar among the sub-groups.

Study details: This post hoc analysis included patients with active PsA (n = 1,281 and n = 423, respectively) from the SELECT-PsA 1 and SELECT-PsA 2 trials who were randomly assigned to receive either 15 mg upadacitinib, placebo, or adalimumab and were categorized as those with or without axial involvement.

Disclosures: This study was funded by AbbVie. Five authors declared being employees or stockholders of AbbVie, and some authors reported ties with various sources, including AbbVie.

Source: Baraliakos X et al. Efficacy and safety of upadacitinib in patients with active psoriatic arthritis and axial involvement: Results from two phase 3 studies. Arthritis Res Ther. 2023;25:56 (Apr 10). Doi: 10.1186/s13075-023-03027-5

Key clinical point: Compared with placebo, 15 mg upadacitinib led to a greater improvement in axial symptoms with a consistent safety profile in patients with psoriatic arthritis (PsA).

Major finding: The improvement in overall Bath Ankylosing Spondylitis Disease Activity Index score at week 24 was significantly higher with 15 mg upadacitinib vs placebo in both SELECT-PsA 1 (−3.12 vs −1.70; P < .0001) and SELECT PsA 2 (−2.06 vs −0.21; P < .0001) trials. Treatment-emergent adverse events were generally similar among the sub-groups.

Study details: This post hoc analysis included patients with active PsA (n = 1,281 and n = 423, respectively) from the SELECT-PsA 1 and SELECT-PsA 2 trials who were randomly assigned to receive either 15 mg upadacitinib, placebo, or adalimumab and were categorized as those with or without axial involvement.

Disclosures: This study was funded by AbbVie. Five authors declared being employees or stockholders of AbbVie, and some authors reported ties with various sources, including AbbVie.

Source: Baraliakos X et al. Efficacy and safety of upadacitinib in patients with active psoriatic arthritis and axial involvement: Results from two phase 3 studies. Arthritis Res Ther. 2023;25:56 (Apr 10). Doi: 10.1186/s13075-023-03027-5

Key clinical point: Compared with placebo, 15 mg upadacitinib led to a greater improvement in axial symptoms with a consistent safety profile in patients with psoriatic arthritis (PsA).

Major finding: The improvement in overall Bath Ankylosing Spondylitis Disease Activity Index score at week 24 was significantly higher with 15 mg upadacitinib vs placebo in both SELECT-PsA 1 (−3.12 vs −1.70; P < .0001) and SELECT PsA 2 (−2.06 vs −0.21; P < .0001) trials. Treatment-emergent adverse events were generally similar among the sub-groups.

Study details: This post hoc analysis included patients with active PsA (n = 1,281 and n = 423, respectively) from the SELECT-PsA 1 and SELECT-PsA 2 trials who were randomly assigned to receive either 15 mg upadacitinib, placebo, or adalimumab and were categorized as those with or without axial involvement.

Disclosures: This study was funded by AbbVie. Five authors declared being employees or stockholders of AbbVie, and some authors reported ties with various sources, including AbbVie.

Source: Baraliakos X et al. Efficacy and safety of upadacitinib in patients with active psoriatic arthritis and axial involvement: Results from two phase 3 studies. Arthritis Res Ther. 2023;25:56 (Apr 10). Doi: 10.1186/s13075-023-03027-5

Key clinical point: Sonographic enthesitis showed strong association with sonographic synovitis and tenosynovitis in patients with psoriatic arthritis (PsA), suggesting the clinical significance of sonographic enthesitis as a potential marker for inflammation in other musculoskeletal domains.

Major finding: Sonographic enthesitis was significantly associated with sonographic synovitis (β 0.19; P  =  .004) and sonographic tenosynovitis (β 0.1; P  =  .003) and showed strong correlation with patient-reported outcomes, such as Health Assessment Questionnaire (P  =  .003), morning stiffness (P  =  .002), and others.

Study details: This study prospectively recruited 158 patients with PsA who underwent sonographic assessment of 52 joints, 40 tendons, and 14 entheses points along with clinical evaluation.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Balulu G et al. The association between sonographic enthesitis with sonographic synovitis and tenosynovitis in psoriatic arthritis patients. Rheumatology (Oxford). 2023 (May 11). Doi: 10.1093/rheumatology/kead202

Key clinical point: Sonographic enthesitis showed strong association with sonographic synovitis and tenosynovitis in patients with psoriatic arthritis (PsA), suggesting the clinical significance of sonographic enthesitis as a potential marker for inflammation in other musculoskeletal domains.

Major finding: Sonographic enthesitis was significantly associated with sonographic synovitis (β 0.19; P  =  .004) and sonographic tenosynovitis (β 0.1; P  =  .003) and showed strong correlation with patient-reported outcomes, such as Health Assessment Questionnaire (P  =  .003), morning stiffness (P  =  .002), and others.

Study details: This study prospectively recruited 158 patients with PsA who underwent sonographic assessment of 52 joints, 40 tendons, and 14 entheses points along with clinical evaluation.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Balulu G et al. The association between sonographic enthesitis with sonographic synovitis and tenosynovitis in psoriatic arthritis patients. Rheumatology (Oxford). 2023 (May 11). Doi: 10.1093/rheumatology/kead202

Key clinical point: Sonographic enthesitis showed strong association with sonographic synovitis and tenosynovitis in patients with psoriatic arthritis (PsA), suggesting the clinical significance of sonographic enthesitis as a potential marker for inflammation in other musculoskeletal domains.

Major finding: Sonographic enthesitis was significantly associated with sonographic synovitis (β 0.19; P  =  .004) and sonographic tenosynovitis (β 0.1; P  =  .003) and showed strong correlation with patient-reported outcomes, such as Health Assessment Questionnaire (P  =  .003), morning stiffness (P  =  .002), and others.

Study details: This study prospectively recruited 158 patients with PsA who underwent sonographic assessment of 52 joints, 40 tendons, and 14 entheses points along with clinical evaluation.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Balulu G et al. The association between sonographic enthesitis with sonographic synovitis and tenosynovitis in psoriatic arthritis patients. Rheumatology (Oxford). 2023 (May 11). Doi: 10.1093/rheumatology/kead202

Key clinical point: Patients with psoriatic arthritis (PsA) achieved enthesitis resolution over 52 weeks with secukinumab treatment, which was comparable to that with adalimumab treatment.

Major finding: At week 52, secukinumab vs adalimumab led to a similar proportion of patients achieving enthesitis resolution (53.2% vs 51.4%) along with site-specific resolution of lateral epicondyle enthesitis (84.6% vs 87.1%) and showing relapse after first resolution (21.0% vs 15.6%), as assessed by the Spondyloarthritis Research Consortium of Canada Enthesitis Index (SPARCC). Moreover, secukinumab vs adalimumab had a comparable response time to SPARCC enthesitis resolution (113 vs 88 days).

Study details: This post hoc analysis of the EXCEED study included 853 patients with PsA who received either secukinumab (300 mg) or adalimumab (40 mg) over 52 weeks.

Disclosures: This study was supported by Novartis Pharmaceuticals Corporation, USA. C Gaillez and B Parikh declared being current or former employees of Novartis Pharma or Novartis Pharmaceuticals Corporation, and several authors reported ties with various sources, including Novartis.

Source: Kaeley GS et al. Enthesitis in patients with psoriatic arthritis treated with secukinumab or adalimumab: A post hoc analysis of the EXCEED study. Rheumatology (Oxford). 2023 (Apr 25). Doi: 10.1093/rheumatology/kead181

Key clinical point: Patients with psoriatic arthritis (PsA) achieved enthesitis resolution over 52 weeks with secukinumab treatment, which was comparable to that with adalimumab treatment.

Major finding: At week 52, secukinumab vs adalimumab led to a similar proportion of patients achieving enthesitis resolution (53.2% vs 51.4%) along with site-specific resolution of lateral epicondyle enthesitis (84.6% vs 87.1%) and showing relapse after first resolution (21.0% vs 15.6%), as assessed by the Spondyloarthritis Research Consortium of Canada Enthesitis Index (SPARCC). Moreover, secukinumab vs adalimumab had a comparable response time to SPARCC enthesitis resolution (113 vs 88 days).

Study details: This post hoc analysis of the EXCEED study included 853 patients with PsA who received either secukinumab (300 mg) or adalimumab (40 mg) over 52 weeks.

Disclosures: This study was supported by Novartis Pharmaceuticals Corporation, USA. C Gaillez and B Parikh declared being current or former employees of Novartis Pharma or Novartis Pharmaceuticals Corporation, and several authors reported ties with various sources, including Novartis.

Source: Kaeley GS et al. Enthesitis in patients with psoriatic arthritis treated with secukinumab or adalimumab: A post hoc analysis of the EXCEED study. Rheumatology (Oxford). 2023 (Apr 25). Doi: 10.1093/rheumatology/kead181

Key clinical point: Patients with psoriatic arthritis (PsA) achieved enthesitis resolution over 52 weeks with secukinumab treatment, which was comparable to that with adalimumab treatment.

Major finding: At week 52, secukinumab vs adalimumab led to a similar proportion of patients achieving enthesitis resolution (53.2% vs 51.4%) along with site-specific resolution of lateral epicondyle enthesitis (84.6% vs 87.1%) and showing relapse after first resolution (21.0% vs 15.6%), as assessed by the Spondyloarthritis Research Consortium of Canada Enthesitis Index (SPARCC). Moreover, secukinumab vs adalimumab had a comparable response time to SPARCC enthesitis resolution (113 vs 88 days).

Study details: This post hoc analysis of the EXCEED study included 853 patients with PsA who received either secukinumab (300 mg) or adalimumab (40 mg) over 52 weeks.

Disclosures: This study was supported by Novartis Pharmaceuticals Corporation, USA. C Gaillez and B Parikh declared being current or former employees of Novartis Pharma or Novartis Pharmaceuticals Corporation, and several authors reported ties with various sources, including Novartis.

Source: Kaeley GS et al. Enthesitis in patients with psoriatic arthritis treated with secukinumab or adalimumab: A post hoc analysis of the EXCEED study. Rheumatology (Oxford). 2023 (Apr 25). Doi: 10.1093/rheumatology/kead181

Key clinical point: The achievement of stringent treatment goals with secukinumab led to clinically meaningful benefits in physical function in patients with psoriatic arthritis (PsA), with secukinumab showing a protective effect on radiographic progression.

Major finding: Overall, over 2 years, a relatively small percentage of patients receiving secukinumab achieved sustained remission (REM) according to very low disease activity (LDA; 19%-24%) or Disease Activity index for PsA (DAPSA) REM (30%-36%), with those achieving DAPSA LDA+REM or DAPSA REM showing numerically greater improvement in physical function. A higher proportion of secukinumab-treated patients were non-structural progressors at 2 years irrespective of achieving sustained LDA/REM.

Study details: This was a retrospective analysis from the FUTURE 5 study including 996 patients with active PsA who were randomly assigned to receive secukinumab or placebo.

Disclosures: This study was funded by Novartis Pharma AG. Two authors declared being employees of or owning stocks/shares in Novartis, and several authors reported ties with various sources, including Novartis.

Source: Coates LC et al. Secukinumab improves physical function and quality of life and inhibits structural damage in patients with PsA with sustained remission or low disease activity: Results from the 2-year phase 3 FUTURE 5 study. RMD Open. 2023;9(2):e002939 (Apr 24). Doi: 10.1136/rmdopen-2022-002939

Key clinical point: The achievement of stringent treatment goals with secukinumab led to clinically meaningful benefits in physical function in patients with psoriatic arthritis (PsA), with secukinumab showing a protective effect on radiographic progression.

Major finding: Overall, over 2 years, a relatively small percentage of patients receiving secukinumab achieved sustained remission (REM) according to very low disease activity (LDA; 19%-24%) or Disease Activity index for PsA (DAPSA) REM (30%-36%), with those achieving DAPSA LDA+REM or DAPSA REM showing numerically greater improvement in physical function. A higher proportion of secukinumab-treated patients were non-structural progressors at 2 years irrespective of achieving sustained LDA/REM.

Study details: This was a retrospective analysis from the FUTURE 5 study including 996 patients with active PsA who were randomly assigned to receive secukinumab or placebo.

Disclosures: This study was funded by Novartis Pharma AG. Two authors declared being employees of or owning stocks/shares in Novartis, and several authors reported ties with various sources, including Novartis.

Source: Coates LC et al. Secukinumab improves physical function and quality of life and inhibits structural damage in patients with PsA with sustained remission or low disease activity: Results from the 2-year phase 3 FUTURE 5 study. RMD Open. 2023;9(2):e002939 (Apr 24). Doi: 10.1136/rmdopen-2022-002939

Key clinical point: The achievement of stringent treatment goals with secukinumab led to clinically meaningful benefits in physical function in patients with psoriatic arthritis (PsA), with secukinumab showing a protective effect on radiographic progression.

Major finding: Overall, over 2 years, a relatively small percentage of patients receiving secukinumab achieved sustained remission (REM) according to very low disease activity (LDA; 19%-24%) or Disease Activity index for PsA (DAPSA) REM (30%-36%), with those achieving DAPSA LDA+REM or DAPSA REM showing numerically greater improvement in physical function. A higher proportion of secukinumab-treated patients were non-structural progressors at 2 years irrespective of achieving sustained LDA/REM.

Study details: This was a retrospective analysis from the FUTURE 5 study including 996 patients with active PsA who were randomly assigned to receive secukinumab or placebo.

Disclosures: This study was funded by Novartis Pharma AG. Two authors declared being employees of or owning stocks/shares in Novartis, and several authors reported ties with various sources, including Novartis.

Source: Coates LC et al. Secukinumab improves physical function and quality of life and inhibits structural damage in patients with PsA with sustained remission or low disease activity: Results from the 2-year phase 3 FUTURE 5 study. RMD Open. 2023;9(2):e002939 (Apr 24). Doi: 10.1136/rmdopen-2022-002939

The investigational drug brepocitinib showed superior symptom reduction in adults with moderate to severe active psoriatic arthritis (PsA), compared with placebo, by meeting primary and secondary endpoints of a phase 2b trial at 16 weeks, which persisted out to 1 year, according to data from 218 individuals.

Brepocitinib, a combination tyrosine kinase 2 and Janus kinase 1 inhibitor, is being studied for the treatment of several immunologic diseases including PsA, wrote Philip Mease, MD, of the Swedish Medical Center/Providence St. Joseph Health and the University of Washington, both in Seattle.

Previous studies in patients with PsA support the use of Janus kinase inhibitors and demonstrate the efficacy of tyrosine kinase 2 inhibitors, but more data are needed in patients with active PsA, the researchers noted.

In a study published in Arthritis & Rheumatology, the researchers randomized adults aged 18-75 years with moderate to severe PsA to once-daily oral doses of brepocitinib at 10 mg, 30 mg, or 60 mg, or a placebo for 16 weeks to assess safety, efficacy, and dose response. Placebo-treated patients were advanced to 30 mg or 60 mg of brepocitinib at week 16. Baseline demographics and disease characteristics were similar among the treatment groups. The mean Psoriatic Arthritis Disease Activity Score (PASDAS) and Disease Activity Index for PsA scores were 5.6 and 38.2, respectively, for the overall study population. Approximately two-thirds (64.7%) had a baseline Psoriasis Area and Severity Index (PASI) score greater than 0 and 3% or more of their body surface area affected by psoriasis.

The primary endpoint was the proportion of patients achieving 20% improvement in American College of Rheumatology response criteria (ACR 20) at week 16. Secondary endpoints included rates of patients meeting ACR 50 and ACR 70 response criteria, the proportion of patients achieving 75% and 90% improvement in PASI scores (PASI 70 and 90), as well as the rates of patients meeting Minimal Disease Activity (MDA) criteria at 16 and 52 weeks.

At week 16, ACR 20 response rates were significantly higher in the brepocitinib 30-mg and 60-mg groups, compared with the placebo group (66.7% and 74.6%, respectively, vs. 43.3%), but not for those who received brepocitinib 10 mg (64.5%).

Response rates for ACR 50, ACR 70, PASI 75, PASI 90, and MDA were similarly higher in the 30-mg and 60-mg brepocitinib groups, compared with placebo, and these responses persisted at week 52. Notably, significant differences in PASI 75 and PASI 90 were observed in patients taking 30 mg and 60 mg brepocitinib, compared with placebo, as early as weeks 4 and 8, respectively, the researchers said.

In addition, disease activity based on PASDAS improved significantly more from baseline to week 16 in all brepocitinib groups, compared with placebo.

The overall safety data were consistent with previous brepocitinib studies, and most of the adverse events were mild or moderate, the researchers said. A total of 12 participants (5.5%) experienced a total of 15 serious adverse events, including 6 infections with brepocitinib 30 mg or 60 mg. No major adverse cardiovascular events or deaths occurred during the study period.

The findings were limited by several factors, including the use of clinics in a limited geographic area (11 countries in Europe), small sample size, and mainly White population, the researchers noted. Other limitations included the large placebo effect and relatively short placebo-controlled period.

The study was supported by Pfizer. Dr. Mease disclosed relationships with Pfizer and other companies including AbbVie, Amgen, Bristol-Myers Squibb, Boehringer Ingelheim, Galapagos, Gilead, GlaxoSmithKline, Inmagene, Janssen, Lilly, Novartis, Sun, and UCB. Many coauthors were employees of Pfizer, and others reported financial relationships with Pfizer and other pharmaceutical companies.

The investigational drug brepocitinib showed superior symptom reduction in adults with moderate to severe active psoriatic arthritis (PsA), compared with placebo, by meeting primary and secondary endpoints of a phase 2b trial at 16 weeks, which persisted out to 1 year, according to data from 218 individuals.

Brepocitinib, a combination tyrosine kinase 2 and Janus kinase 1 inhibitor, is being studied for the treatment of several immunologic diseases including PsA, wrote Philip Mease, MD, of the Swedish Medical Center/Providence St. Joseph Health and the University of Washington, both in Seattle.

Previous studies in patients with PsA support the use of Janus kinase inhibitors and demonstrate the efficacy of tyrosine kinase 2 inhibitors, but more data are needed in patients with active PsA, the researchers noted.

In a study published in Arthritis & Rheumatology, the researchers randomized adults aged 18-75 years with moderate to severe PsA to once-daily oral doses of brepocitinib at 10 mg, 30 mg, or 60 mg, or a placebo for 16 weeks to assess safety, efficacy, and dose response. Placebo-treated patients were advanced to 30 mg or 60 mg of brepocitinib at week 16. Baseline demographics and disease characteristics were similar among the treatment groups. The mean Psoriatic Arthritis Disease Activity Score (PASDAS) and Disease Activity Index for PsA scores were 5.6 and 38.2, respectively, for the overall study population. Approximately two-thirds (64.7%) had a baseline Psoriasis Area and Severity Index (PASI) score greater than 0 and 3% or more of their body surface area affected by psoriasis.

The primary endpoint was the proportion of patients achieving 20% improvement in American College of Rheumatology response criteria (ACR 20) at week 16. Secondary endpoints included rates of patients meeting ACR 50 and ACR 70 response criteria, the proportion of patients achieving 75% and 90% improvement in PASI scores (PASI 70 and 90), as well as the rates of patients meeting Minimal Disease Activity (MDA) criteria at 16 and 52 weeks.

At week 16, ACR 20 response rates were significantly higher in the brepocitinib 30-mg and 60-mg groups, compared with the placebo group (66.7% and 74.6%, respectively, vs. 43.3%), but not for those who received brepocitinib 10 mg (64.5%).

Response rates for ACR 50, ACR 70, PASI 75, PASI 90, and MDA were similarly higher in the 30-mg and 60-mg brepocitinib groups, compared with placebo, and these responses persisted at week 52. Notably, significant differences in PASI 75 and PASI 90 were observed in patients taking 30 mg and 60 mg brepocitinib, compared with placebo, as early as weeks 4 and 8, respectively, the researchers said.

In addition, disease activity based on PASDAS improved significantly more from baseline to week 16 in all brepocitinib groups, compared with placebo.

The overall safety data were consistent with previous brepocitinib studies, and most of the adverse events were mild or moderate, the researchers said. A total of 12 participants (5.5%) experienced a total of 15 serious adverse events, including 6 infections with brepocitinib 30 mg or 60 mg. No major adverse cardiovascular events or deaths occurred during the study period.

The findings were limited by several factors, including the use of clinics in a limited geographic area (11 countries in Europe), small sample size, and mainly White population, the researchers noted. Other limitations included the large placebo effect and relatively short placebo-controlled period.

The study was supported by Pfizer. Dr. Mease disclosed relationships with Pfizer and other companies including AbbVie, Amgen, Bristol-Myers Squibb, Boehringer Ingelheim, Galapagos, Gilead, GlaxoSmithKline, Inmagene, Janssen, Lilly, Novartis, Sun, and UCB. Many coauthors were employees of Pfizer, and others reported financial relationships with Pfizer and other pharmaceutical companies.

The investigational drug brepocitinib showed superior symptom reduction in adults with moderate to severe active psoriatic arthritis (PsA), compared with placebo, by meeting primary and secondary endpoints of a phase 2b trial at 16 weeks, which persisted out to 1 year, according to data from 218 individuals.

Brepocitinib, a combination tyrosine kinase 2 and Janus kinase 1 inhibitor, is being studied for the treatment of several immunologic diseases including PsA, wrote Philip Mease, MD, of the Swedish Medical Center/Providence St. Joseph Health and the University of Washington, both in Seattle.

Previous studies in patients with PsA support the use of Janus kinase inhibitors and demonstrate the efficacy of tyrosine kinase 2 inhibitors, but more data are needed in patients with active PsA, the researchers noted.

In a study published in Arthritis & Rheumatology, the researchers randomized adults aged 18-75 years with moderate to severe PsA to once-daily oral doses of brepocitinib at 10 mg, 30 mg, or 60 mg, or a placebo for 16 weeks to assess safety, efficacy, and dose response. Placebo-treated patients were advanced to 30 mg or 60 mg of brepocitinib at week 16. Baseline demographics and disease characteristics were similar among the treatment groups. The mean Psoriatic Arthritis Disease Activity Score (PASDAS) and Disease Activity Index for PsA scores were 5.6 and 38.2, respectively, for the overall study population. Approximately two-thirds (64.7%) had a baseline Psoriasis Area and Severity Index (PASI) score greater than 0 and 3% or more of their body surface area affected by psoriasis.

The primary endpoint was the proportion of patients achieving 20% improvement in American College of Rheumatology response criteria (ACR 20) at week 16. Secondary endpoints included rates of patients meeting ACR 50 and ACR 70 response criteria, the proportion of patients achieving 75% and 90% improvement in PASI scores (PASI 70 and 90), as well as the rates of patients meeting Minimal Disease Activity (MDA) criteria at 16 and 52 weeks.

At week 16, ACR 20 response rates were significantly higher in the brepocitinib 30-mg and 60-mg groups, compared with the placebo group (66.7% and 74.6%, respectively, vs. 43.3%), but not for those who received brepocitinib 10 mg (64.5%).

Response rates for ACR 50, ACR 70, PASI 75, PASI 90, and MDA were similarly higher in the 30-mg and 60-mg brepocitinib groups, compared with placebo, and these responses persisted at week 52. Notably, significant differences in PASI 75 and PASI 90 were observed in patients taking 30 mg and 60 mg brepocitinib, compared with placebo, as early as weeks 4 and 8, respectively, the researchers said.

In addition, disease activity based on PASDAS improved significantly more from baseline to week 16 in all brepocitinib groups, compared with placebo.

The overall safety data were consistent with previous brepocitinib studies, and most of the adverse events were mild or moderate, the researchers said. A total of 12 participants (5.5%) experienced a total of 15 serious adverse events, including 6 infections with brepocitinib 30 mg or 60 mg. No major adverse cardiovascular events or deaths occurred during the study period.

The findings were limited by several factors, including the use of clinics in a limited geographic area (11 countries in Europe), small sample size, and mainly White population, the researchers noted. Other limitations included the large placebo effect and relatively short placebo-controlled period.

The study was supported by Pfizer. Dr. Mease disclosed relationships with Pfizer and other companies including AbbVie, Amgen, Bristol-Myers Squibb, Boehringer Ingelheim, Galapagos, Gilead, GlaxoSmithKline, Inmagene, Janssen, Lilly, Novartis, Sun, and UCB. Many coauthors were employees of Pfizer, and others reported financial relationships with Pfizer and other pharmaceutical companies.

Are there clinically significant differences between axial spondyloarthritis with psoriasis and psoriatic arthritis with axial symptoms? Does it matter?

It all depends on whom you ask, but right now the evidence seems to be tipping in favor of the “splitters” who cite evidence supporting their contention that axial spondyloarthritis (axSpA)/ankylosing spondylitis (AS) with psoriasis and psoriatic arthritis (PsA) with axial symptoms are distinct clinical entities that require more precise diagnosis and treatment.

“Lumpers,” in contrast, argue that they are different points on the same clinical spectrum.

The debate is not just of academic interest, but has real consequences for patients, say specialists on both sides of the aisle.
 

Overlapping features, different presentations

“Axial SpA and axPsA have overlapping features but also meaningful differences in genetics, clinical presentation, imaging, and immunophenotype. Efforts are underway to develop classification criteria for axPsA to aid research efforts as well as clinical diagnosis and management,” Philip J. Mease, MD, director of rheumatology research at Swedish Medical Center/Providence–St. Joseph Health in Seattle, and colleagues contend.

In an editorial published in the International Journal of Rheumatic Diseases, Dr. Mease and colleagues noted that, although HLA-B*27 is a genetic risk factor for both axPsA and axSpA, some HLA-B alleles are significantly associated with axPsA, whereas other alleles are associated with axSpA.

In addition, while genes in the interleukin-23 and IL-17 pathway are associated with increased risk for axSpA, genes in the IL-13 pathway have been identified as risk markers for axPsA, they noted.
 

Two cohorts better than one?

Dafna Gladman, MD, professor of medicine at the University of Toronto and senior scientist at the Schroeder Arthritis Institute at Toronto Western Hospital, and colleagues have a unique perspective on the similarities and differences between the disease entities.

Her group’s research uses data on cohorts of patients treated in two separate clinics at Toronto Western Hospital: one for patients with PsA, and one for patients with axial spondyloarthritis, including those with ankylosing spondylitis, nonradiographic axSpA, and spondylitis associated with inflammatory bowel disease.

“Our work has shown that there are differences, and one of the reasons that it’s now important is that the anti–IL-23 medications, both the IL-12/23 inhibitor ustekinumab [Stelara] and the IL-23 inhibitor guselkumab [Tremfya] work for psoriatic arthritis, whereas IL-23 did not work in ankylosing spondylitis, so that provided further impetus to look into the distinction between the two groups,” Dr. Gladman said in an interview.

Dr. Gladman and colleagues published a study in Rheumatology in which they compared clinical presentations and features of patients with AS with or without psoriasis with patients with axPsA.

They found that patients with AS with or without psoriasis tended to be younger, had a higher proportion of males to females, and were more likely to be positive for HLA-B*27. Patients with AS also had more back pain at presentation, worse axial disease activity scores, worse global assessments by physicians, and higher grades of sacroiliitis, and they were more likely to be taking biologic agents.

“What that showed, right off the top, that whether we’re looking at the total group or we’re looking specifically at those patients who have psoriasis or don’t have psoriasis, they are different from those with psoriatic arthritis with axial disease,” she said.

They concluded that “axPsA seems to be a distinct entity.”
 

Two clinics, same presentation

Because the aforementioned study included all patients with PsA with or without peripheral disease, the investigators decided to filter out some of the background noise and conduct a second study in which they compared patients who presented to the two clinics with the same presentation, either with spinal disease and psoriasis to the spondylitis clinic, or with psoriasis and isolated axial disease to the PsA clinic.

The results, published in Annals of the Rheumatic Diseases, showed that just 2.03% of patients with PsA had isolated axial disease, and an additional 29.38% had axial and peripheral disease.

In this study, “you can see that even in that group there are distinct differences. The patients that are labeled psoriatic spondylitis are different from those that are labeled ankylosing spondylitis with psoriasis,” Dr. Gladman said.

Isolated axial disease in patients with PsA was associated with HLA-B*27 positivity and lower Health Assessment Questionnaire scores. In addition, patients who were HLA-B*27 positive also had a nearly eightfold higher risk for developing peripheral disease over time.

Patients with isolated axial PsA were significantly more likely to be diagnosed at an older age (mean, 37.44 vs. 29.65 years), had higher Psoriasis Area Severity Index scores and a higher likelihood of having psoriatic nail lesions than patients with AS with isolated axial disease and psoriasis.

In contrast, patients with isolated axSpA with psoriasis were more likely to have inflammatory back pain, spinal pain, joint pain/swelling, and areas of localized tenderness, and they had greater severity of morning stiffness.

Dr. Gladman noted that, although AS and PsA are associated with the same gene that encodes for the IL-23 receptor, each condition is associated with a different single-nucleotide polymorphism.

Same disease, different flavors?

But as Mark Twain said, it is difference of opinion that makes horse races, and some specialists in rheumatology say that axSpA amd axPsA are just two sides of the same coin.

Pramod Rathod

“There are always different schools of thought. I believe that they are not different diseases, but a spectrum of diseases,” said Shailendra Singh, MD, a rheumatologist at Unity Health Medical Center in Searcy, Ark., and past president of the Arkansas Rheumatology Association.

In an interview, Dr. Singh said that the spectrum ranges from diseases with primarily axial involvement, such as AS, to those with primarily peripheral involvement, such as reactive arthritis.

He pointed out that these conditions have overlapping symptoms, including enthesitis, dactylitis, and uveitis, and inflammatory arthritis.

Daniel Wendling, MD, PhD, from the Centre Hospitalier Régional Universitaire de Besançon (France), Université de Franche-Comté, and colleagues agreed.

“The criteria currently available for both SpA [ASAS (Assessment of Spondyloarthritis International Society) criteria] and PsA [CASPAR (Classification for Psoriatic Arthritis) criteria] are classification criteria, not diagnostic criteria. They are not very stringent and are not exclusive. Thus, the same patient can easily be classified simultaneously in both entities, making the distinction between axSpA with psoriasis and axPsA theoretical,” they wrote in an editorial published in Joint Bone Spine.

They cited as an example of the allegedly fuzzy criteria a prospective study conducted by the investigators in Bath, England, in which modified New York criteria for AS were met by 24% of patients with AS, and CASPAR criteria for PsA were met by an equal number of patients with AS.
 

Therapeutic implications

Dr. Wendling and colleagues acknowledge the differences cited in studies by Dr. Gladman, Dr. Mease, and others between patients with axPsA and those with axSpA, but argue that the differences are not that great and not so clear.

“It should also be emphasized that, although some differences between axPsA and axSpA reach statistical significance, they are mostly at the margin, with low odd ratios,” they wrote.

“It is also important to consider the variability in the definition of axPsA, sometimes simply ‘physician reported’ and elsewhere based on the modified New York radiographic criteria; the latter are only present late in the course of the disease, and this may induce bias,” they continued.

Dr. Singh agreed that, as noted by Dr. Gladman, some patients will respond to anti–IL-17, anti–IL-23, and anti–IL-12/23 agents, whereas others will have better responses with tumor necrosis factor (TNF) inhibitors, and still others, such as those with peripheral involvement in the hands and feet may fare better with nonbiologic disease-modifying antirheumatic drugs such as methotrexate.
 

Answers to come?

Dr. Gladman noted that the information available to date about the efficacy of IL-23 inhibition in axPsA is based on a post hoc analysis of the PSUMMIT 1 and 2 controlled trials in PsA, and is not definitive.

The randomized, controlled STAR trial, currently recruiting patients, is designed to see whether guselkumab can reduce axial symptoms and inflammation in patients with active axPsA.

“What I say is, there is a rationale for [anti–IL-23] to work in psoriatic arthritis, and not work in ankylosing spondylitis,” she said.

In contrast, IL-17 inhibitors, anti-TNF agents, and Janus kinase inhibitors show efficacy against both axPsA and AS. Rituximab is ineffective against PsA, but has shown efficacy against AS, especially in patients with neurologic complications from anti-TNF agents.

“There may be other medications that would work more specifically in axial psoriatic arthritis that don’t work in ankylosing spondylitis, but at least recognizing that there may be some differences, and that therefore a correct diagnosis should be obtained, might be important,” she said.

Ideally, the picture will become clearer with results from the ongoing Axial Involvement in Psoriatic Arthritis cohort, a joint project of ASAS and the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. The multinational, cross-sectional study is designed “to systematically evaluate clinical and imaging manifestations indicative of axial involvement in patients with PsA and to develop classification criteria and a unified nomenclature for axial involvement in PsA that would allow defining a homogeneous subgroup of patients for research.”

Stay tuned.

Dr. Gladman’s research is supported by a grant from the Krembil Foundation. Dr. Singh disclosed research support from various companies. Funding sources and conflict of interest disclosures from other works cited are contained in their respective references.

Are there clinically significant differences between axial spondyloarthritis with psoriasis and psoriatic arthritis with axial symptoms? Does it matter?

It all depends on whom you ask, but right now the evidence seems to be tipping in favor of the “splitters” who cite evidence supporting their contention that axial spondyloarthritis (axSpA)/ankylosing spondylitis (AS) with psoriasis and psoriatic arthritis (PsA) with axial symptoms are distinct clinical entities that require more precise diagnosis and treatment.

“Lumpers,” in contrast, argue that they are different points on the same clinical spectrum.

The debate is not just of academic interest, but has real consequences for patients, say specialists on both sides of the aisle.
 

Overlapping features, different presentations

“Axial SpA and axPsA have overlapping features but also meaningful differences in genetics, clinical presentation, imaging, and immunophenotype. Efforts are underway to develop classification criteria for axPsA to aid research efforts as well as clinical diagnosis and management,” Philip J. Mease, MD, director of rheumatology research at Swedish Medical Center/Providence–St. Joseph Health in Seattle, and colleagues contend.

In an editorial published in the International Journal of Rheumatic Diseases, Dr. Mease and colleagues noted that, although HLA-B*27 is a genetic risk factor for both axPsA and axSpA, some HLA-B alleles are significantly associated with axPsA, whereas other alleles are associated with axSpA.

In addition, while genes in the interleukin-23 and IL-17 pathway are associated with increased risk for axSpA, genes in the IL-13 pathway have been identified as risk markers for axPsA, they noted.
 

Two cohorts better than one?

Dafna Gladman, MD, professor of medicine at the University of Toronto and senior scientist at the Schroeder Arthritis Institute at Toronto Western Hospital, and colleagues have a unique perspective on the similarities and differences between the disease entities.

Her group’s research uses data on cohorts of patients treated in two separate clinics at Toronto Western Hospital: one for patients with PsA, and one for patients with axial spondyloarthritis, including those with ankylosing spondylitis, nonradiographic axSpA, and spondylitis associated with inflammatory bowel disease.

“Our work has shown that there are differences, and one of the reasons that it’s now important is that the anti–IL-23 medications, both the IL-12/23 inhibitor ustekinumab [Stelara] and the IL-23 inhibitor guselkumab [Tremfya] work for psoriatic arthritis, whereas IL-23 did not work in ankylosing spondylitis, so that provided further impetus to look into the distinction between the two groups,” Dr. Gladman said in an interview.

Dr. Gladman and colleagues published a study in Rheumatology in which they compared clinical presentations and features of patients with AS with or without psoriasis with patients with axPsA.

They found that patients with AS with or without psoriasis tended to be younger, had a higher proportion of males to females, and were more likely to be positive for HLA-B*27. Patients with AS also had more back pain at presentation, worse axial disease activity scores, worse global assessments by physicians, and higher grades of sacroiliitis, and they were more likely to be taking biologic agents.

“What that showed, right off the top, that whether we’re looking at the total group or we’re looking specifically at those patients who have psoriasis or don’t have psoriasis, they are different from those with psoriatic arthritis with axial disease,” she said.

They concluded that “axPsA seems to be a distinct entity.”
 

Two clinics, same presentation

Because the aforementioned study included all patients with PsA with or without peripheral disease, the investigators decided to filter out some of the background noise and conduct a second study in which they compared patients who presented to the two clinics with the same presentation, either with spinal disease and psoriasis to the spondylitis clinic, or with psoriasis and isolated axial disease to the PsA clinic.

The results, published in Annals of the Rheumatic Diseases, showed that just 2.03% of patients with PsA had isolated axial disease, and an additional 29.38% had axial and peripheral disease.

In this study, “you can see that even in that group there are distinct differences. The patients that are labeled psoriatic spondylitis are different from those that are labeled ankylosing spondylitis with psoriasis,” Dr. Gladman said.

Isolated axial disease in patients with PsA was associated with HLA-B*27 positivity and lower Health Assessment Questionnaire scores. In addition, patients who were HLA-B*27 positive also had a nearly eightfold higher risk for developing peripheral disease over time.

Patients with isolated axial PsA were significantly more likely to be diagnosed at an older age (mean, 37.44 vs. 29.65 years), had higher Psoriasis Area Severity Index scores and a higher likelihood of having psoriatic nail lesions than patients with AS with isolated axial disease and psoriasis.

In contrast, patients with isolated axSpA with psoriasis were more likely to have inflammatory back pain, spinal pain, joint pain/swelling, and areas of localized tenderness, and they had greater severity of morning stiffness.

Dr. Gladman noted that, although AS and PsA are associated with the same gene that encodes for the IL-23 receptor, each condition is associated with a different single-nucleotide polymorphism.

Same disease, different flavors?

But as Mark Twain said, it is difference of opinion that makes horse races, and some specialists in rheumatology say that axSpA amd axPsA are just two sides of the same coin.

Pramod Rathod

“There are always different schools of thought. I believe that they are not different diseases, but a spectrum of diseases,” said Shailendra Singh, MD, a rheumatologist at Unity Health Medical Center in Searcy, Ark., and past president of the Arkansas Rheumatology Association.

In an interview, Dr. Singh said that the spectrum ranges from diseases with primarily axial involvement, such as AS, to those with primarily peripheral involvement, such as reactive arthritis.

He pointed out that these conditions have overlapping symptoms, including enthesitis, dactylitis, and uveitis, and inflammatory arthritis.

Daniel Wendling, MD, PhD, from the Centre Hospitalier Régional Universitaire de Besançon (France), Université de Franche-Comté, and colleagues agreed.

“The criteria currently available for both SpA [ASAS (Assessment of Spondyloarthritis International Society) criteria] and PsA [CASPAR (Classification for Psoriatic Arthritis) criteria] are classification criteria, not diagnostic criteria. They are not very stringent and are not exclusive. Thus, the same patient can easily be classified simultaneously in both entities, making the distinction between axSpA with psoriasis and axPsA theoretical,” they wrote in an editorial published in Joint Bone Spine.

They cited as an example of the allegedly fuzzy criteria a prospective study conducted by the investigators in Bath, England, in which modified New York criteria for AS were met by 24% of patients with AS, and CASPAR criteria for PsA were met by an equal number of patients with AS.
 

Therapeutic implications

Dr. Wendling and colleagues acknowledge the differences cited in studies by Dr. Gladman, Dr. Mease, and others between patients with axPsA and those with axSpA, but argue that the differences are not that great and not so clear.

“It should also be emphasized that, although some differences between axPsA and axSpA reach statistical significance, they are mostly at the margin, with low odd ratios,” they wrote.

“It is also important to consider the variability in the definition of axPsA, sometimes simply ‘physician reported’ and elsewhere based on the modified New York radiographic criteria; the latter are only present late in the course of the disease, and this may induce bias,” they continued.

Dr. Singh agreed that, as noted by Dr. Gladman, some patients will respond to anti–IL-17, anti–IL-23, and anti–IL-12/23 agents, whereas others will have better responses with tumor necrosis factor (TNF) inhibitors, and still others, such as those with peripheral involvement in the hands and feet may fare better with nonbiologic disease-modifying antirheumatic drugs such as methotrexate.
 

Answers to come?

Dr. Gladman noted that the information available to date about the efficacy of IL-23 inhibition in axPsA is based on a post hoc analysis of the PSUMMIT 1 and 2 controlled trials in PsA, and is not definitive.

The randomized, controlled STAR trial, currently recruiting patients, is designed to see whether guselkumab can reduce axial symptoms and inflammation in patients with active axPsA.

“What I say is, there is a rationale for [anti–IL-23] to work in psoriatic arthritis, and not work in ankylosing spondylitis,” she said.

In contrast, IL-17 inhibitors, anti-TNF agents, and Janus kinase inhibitors show efficacy against both axPsA and AS. Rituximab is ineffective against PsA, but has shown efficacy against AS, especially in patients with neurologic complications from anti-TNF agents.

“There may be other medications that would work more specifically in axial psoriatic arthritis that don’t work in ankylosing spondylitis, but at least recognizing that there may be some differences, and that therefore a correct diagnosis should be obtained, might be important,” she said.

Ideally, the picture will become clearer with results from the ongoing Axial Involvement in Psoriatic Arthritis cohort, a joint project of ASAS and the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. The multinational, cross-sectional study is designed “to systematically evaluate clinical and imaging manifestations indicative of axial involvement in patients with PsA and to develop classification criteria and a unified nomenclature for axial involvement in PsA that would allow defining a homogeneous subgroup of patients for research.”

Stay tuned.

Dr. Gladman’s research is supported by a grant from the Krembil Foundation. Dr. Singh disclosed research support from various companies. Funding sources and conflict of interest disclosures from other works cited are contained in their respective references.

Are there clinically significant differences between axial spondyloarthritis with psoriasis and psoriatic arthritis with axial symptoms? Does it matter?

It all depends on whom you ask, but right now the evidence seems to be tipping in favor of the “splitters” who cite evidence supporting their contention that axial spondyloarthritis (axSpA)/ankylosing spondylitis (AS) with psoriasis and psoriatic arthritis (PsA) with axial symptoms are distinct clinical entities that require more precise diagnosis and treatment.

“Lumpers,” in contrast, argue that they are different points on the same clinical spectrum.

The debate is not just of academic interest, but has real consequences for patients, say specialists on both sides of the aisle.
 

Overlapping features, different presentations

“Axial SpA and axPsA have overlapping features but also meaningful differences in genetics, clinical presentation, imaging, and immunophenotype. Efforts are underway to develop classification criteria for axPsA to aid research efforts as well as clinical diagnosis and management,” Philip J. Mease, MD, director of rheumatology research at Swedish Medical Center/Providence–St. Joseph Health in Seattle, and colleagues contend.

In an editorial published in the International Journal of Rheumatic Diseases, Dr. Mease and colleagues noted that, although HLA-B*27 is a genetic risk factor for both axPsA and axSpA, some HLA-B alleles are significantly associated with axPsA, whereas other alleles are associated with axSpA.

In addition, while genes in the interleukin-23 and IL-17 pathway are associated with increased risk for axSpA, genes in the IL-13 pathway have been identified as risk markers for axPsA, they noted.
 

Two cohorts better than one?

Dafna Gladman, MD, professor of medicine at the University of Toronto and senior scientist at the Schroeder Arthritis Institute at Toronto Western Hospital, and colleagues have a unique perspective on the similarities and differences between the disease entities.

Her group’s research uses data on cohorts of patients treated in two separate clinics at Toronto Western Hospital: one for patients with PsA, and one for patients with axial spondyloarthritis, including those with ankylosing spondylitis, nonradiographic axSpA, and spondylitis associated with inflammatory bowel disease.

“Our work has shown that there are differences, and one of the reasons that it’s now important is that the anti–IL-23 medications, both the IL-12/23 inhibitor ustekinumab [Stelara] and the IL-23 inhibitor guselkumab [Tremfya] work for psoriatic arthritis, whereas IL-23 did not work in ankylosing spondylitis, so that provided further impetus to look into the distinction between the two groups,” Dr. Gladman said in an interview.

Dr. Gladman and colleagues published a study in Rheumatology in which they compared clinical presentations and features of patients with AS with or without psoriasis with patients with axPsA.

They found that patients with AS with or without psoriasis tended to be younger, had a higher proportion of males to females, and were more likely to be positive for HLA-B*27. Patients with AS also had more back pain at presentation, worse axial disease activity scores, worse global assessments by physicians, and higher grades of sacroiliitis, and they were more likely to be taking biologic agents.

“What that showed, right off the top, that whether we’re looking at the total group or we’re looking specifically at those patients who have psoriasis or don’t have psoriasis, they are different from those with psoriatic arthritis with axial disease,” she said.

They concluded that “axPsA seems to be a distinct entity.”
 

Two clinics, same presentation

Because the aforementioned study included all patients with PsA with or without peripheral disease, the investigators decided to filter out some of the background noise and conduct a second study in which they compared patients who presented to the two clinics with the same presentation, either with spinal disease and psoriasis to the spondylitis clinic, or with psoriasis and isolated axial disease to the PsA clinic.

The results, published in Annals of the Rheumatic Diseases, showed that just 2.03% of patients with PsA had isolated axial disease, and an additional 29.38% had axial and peripheral disease.

In this study, “you can see that even in that group there are distinct differences. The patients that are labeled psoriatic spondylitis are different from those that are labeled ankylosing spondylitis with psoriasis,” Dr. Gladman said.

Isolated axial disease in patients with PsA was associated with HLA-B*27 positivity and lower Health Assessment Questionnaire scores. In addition, patients who were HLA-B*27 positive also had a nearly eightfold higher risk for developing peripheral disease over time.

Patients with isolated axial PsA were significantly more likely to be diagnosed at an older age (mean, 37.44 vs. 29.65 years), had higher Psoriasis Area Severity Index scores and a higher likelihood of having psoriatic nail lesions than patients with AS with isolated axial disease and psoriasis.

In contrast, patients with isolated axSpA with psoriasis were more likely to have inflammatory back pain, spinal pain, joint pain/swelling, and areas of localized tenderness, and they had greater severity of morning stiffness.

Dr. Gladman noted that, although AS and PsA are associated with the same gene that encodes for the IL-23 receptor, each condition is associated with a different single-nucleotide polymorphism.

Same disease, different flavors?

But as Mark Twain said, it is difference of opinion that makes horse races, and some specialists in rheumatology say that axSpA amd axPsA are just two sides of the same coin.

Pramod Rathod

“There are always different schools of thought. I believe that they are not different diseases, but a spectrum of diseases,” said Shailendra Singh, MD, a rheumatologist at Unity Health Medical Center in Searcy, Ark., and past president of the Arkansas Rheumatology Association.

In an interview, Dr. Singh said that the spectrum ranges from diseases with primarily axial involvement, such as AS, to those with primarily peripheral involvement, such as reactive arthritis.

He pointed out that these conditions have overlapping symptoms, including enthesitis, dactylitis, and uveitis, and inflammatory arthritis.

Daniel Wendling, MD, PhD, from the Centre Hospitalier Régional Universitaire de Besançon (France), Université de Franche-Comté, and colleagues agreed.

“The criteria currently available for both SpA [ASAS (Assessment of Spondyloarthritis International Society) criteria] and PsA [CASPAR (Classification for Psoriatic Arthritis) criteria] are classification criteria, not diagnostic criteria. They are not very stringent and are not exclusive. Thus, the same patient can easily be classified simultaneously in both entities, making the distinction between axSpA with psoriasis and axPsA theoretical,” they wrote in an editorial published in Joint Bone Spine.

They cited as an example of the allegedly fuzzy criteria a prospective study conducted by the investigators in Bath, England, in which modified New York criteria for AS were met by 24% of patients with AS, and CASPAR criteria for PsA were met by an equal number of patients with AS.
 

Therapeutic implications

Dr. Wendling and colleagues acknowledge the differences cited in studies by Dr. Gladman, Dr. Mease, and others between patients with axPsA and those with axSpA, but argue that the differences are not that great and not so clear.

“It should also be emphasized that, although some differences between axPsA and axSpA reach statistical significance, they are mostly at the margin, with low odd ratios,” they wrote.

“It is also important to consider the variability in the definition of axPsA, sometimes simply ‘physician reported’ and elsewhere based on the modified New York radiographic criteria; the latter are only present late in the course of the disease, and this may induce bias,” they continued.

Dr. Singh agreed that, as noted by Dr. Gladman, some patients will respond to anti–IL-17, anti–IL-23, and anti–IL-12/23 agents, whereas others will have better responses with tumor necrosis factor (TNF) inhibitors, and still others, such as those with peripheral involvement in the hands and feet may fare better with nonbiologic disease-modifying antirheumatic drugs such as methotrexate.
 

Answers to come?

Dr. Gladman noted that the information available to date about the efficacy of IL-23 inhibition in axPsA is based on a post hoc analysis of the PSUMMIT 1 and 2 controlled trials in PsA, and is not definitive.

The randomized, controlled STAR trial, currently recruiting patients, is designed to see whether guselkumab can reduce axial symptoms and inflammation in patients with active axPsA.

“What I say is, there is a rationale for [anti–IL-23] to work in psoriatic arthritis, and not work in ankylosing spondylitis,” she said.

In contrast, IL-17 inhibitors, anti-TNF agents, and Janus kinase inhibitors show efficacy against both axPsA and AS. Rituximab is ineffective against PsA, but has shown efficacy against AS, especially in patients with neurologic complications from anti-TNF agents.

“There may be other medications that would work more specifically in axial psoriatic arthritis that don’t work in ankylosing spondylitis, but at least recognizing that there may be some differences, and that therefore a correct diagnosis should be obtained, might be important,” she said.

Ideally, the picture will become clearer with results from the ongoing Axial Involvement in Psoriatic Arthritis cohort, a joint project of ASAS and the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. The multinational, cross-sectional study is designed “to systematically evaluate clinical and imaging manifestations indicative of axial involvement in patients with PsA and to develop classification criteria and a unified nomenclature for axial involvement in PsA that would allow defining a homogeneous subgroup of patients for research.”

Stay tuned.

Dr. Gladman’s research is supported by a grant from the Krembil Foundation. Dr. Singh disclosed research support from various companies. Funding sources and conflict of interest disclosures from other works cited are contained in their respective references.

New research is shedding light on how an infection with COVID-19 may reactivate, or even cause, psoriasis. 

 Psoriasis has several well-established triggers, including stress, skin injury, cold or warm air, and allergies. Illnesses like strep throat can also cause a psoriasis flare in some people – and it appears COVID may also do so. “Psoriasis flares have long been associated with bacterial and viral infections, particularly a form of psoriasis called guttate, which is characterized by tons of tiny red scaly bumps all over the body,” said Joel M. Gelfand, MD, a professor of dermatology and epidemiology at the University of Pennsylvania, Philadelphia. “Infection with COVID-19 has been associated with flares of guttate and pustular psoriasis, and even psoriasis that affects 100% of the skin ... in many published case reports.”

Israeli researchers recently found that psoriasis patients have a slightly higher risk of getting COVID,  although they are not at higher risk of hospitalization or death, which could be related to treatment with immune-modulating therapy, which can increase their risk of infections.
 

How could COVID cause psoriasis to flare? 

Psoriasis is an autoimmune condition, and inflammation can cause symptoms.

Investigators for a study from Albany (N.Y.) Medical College and Weirton (Pa.) Medical Center found that people in the study who were already diagnosed with the skin condition had an unexpected flare within a week to a month after testing positive for COVID. New psoriasis after a COVID infection was also found. The researchers think this could be because COVID causes inflammation in the body, which negatively affects previously well-controlled psoriasis. They also think it’s possible that COVID-related inflammation could trigger a genetic tendency to have psoriasis, which may explain why it can appear for the first time after a positive test.

“A viral infection like COVID-19 can signal the release of proinflammatory factors that can appear as rashes, such as with psoriasis.” said Robert O. Carpenter, MD, director of wellness at Texas A&M University in Bryan.
 

What are the symptoms of COVID-related psoriasis?

The signs are the same as those of any form of psoriasis.
 

For a patient with psoriasis, will COVID automatically make it worse?

Not necessarily.

“Psoriasis is a common condition, so people should be aware that new psoriasis that develops may not be related to COVID-19,” said Esther Freeman MD, PhD, director of global health dermatology at Massachusetts General Hospital in Boston.

As with every aspect of COVID, doctors and scientists are still learning about how serious and widespread a problem psoriasis after COVID-19 may be. “We have seen case reports that psoriasis can flare after COVID-19,” said Dr. Freeman, who is also an associate professor of dermatology at Harvard Medical School. “I will say, this has not been a tidal wave – more like sporadic cases here and there. So I do not think psoriasis flares are a major post-COVID finding, nor do they necessarily mean you have long COVID. That being said, we know that many different infections can cause psoriasis flares, and so, in that respect, it’s not that surprising that SARS-CoV-2, like other infections, could trigger a psoriasis flare.”

Could getting COVID more than once cause psoriasis to flare? It’s possible.

“Your body can change after having COVID-19,” said Dr. Carpenter. “We don’t know the long-term implications, but having COVID-19 repeatedly can increase the risk of long COVID, which can cause many systemic changes in your body.” 

Another important point: For patients who take biologics for treating psoriasis, getting vaccinated and boosted for COVID is an important step to take to help protect themselves.
 

Is psoriasis itself a potential symptom of COVID? 

“Yes, but we don’t know the frequency at which this may occur, and a causal relationship is difficult to establish from just case reports,” said Dr. Gelfand, who’s also medical director of the clinical studies unit in the department of dermatology at his university. “Typically, if a patient presents with a flare of psoriasis, particularly guttate, pustular, or erythrodermic forms, an infectious trigger should be considered, and testing for strep and possibly COVID-19 may be appropriate.”
 

A version of this article first appeared on Medscape.com.

New research is shedding light on how an infection with COVID-19 may reactivate, or even cause, psoriasis. 

 Psoriasis has several well-established triggers, including stress, skin injury, cold or warm air, and allergies. Illnesses like strep throat can also cause a psoriasis flare in some people – and it appears COVID may also do so. “Psoriasis flares have long been associated with bacterial and viral infections, particularly a form of psoriasis called guttate, which is characterized by tons of tiny red scaly bumps all over the body,” said Joel M. Gelfand, MD, a professor of dermatology and epidemiology at the University of Pennsylvania, Philadelphia. “Infection with COVID-19 has been associated with flares of guttate and pustular psoriasis, and even psoriasis that affects 100% of the skin ... in many published case reports.”

Israeli researchers recently found that psoriasis patients have a slightly higher risk of getting COVID,  although they are not at higher risk of hospitalization or death, which could be related to treatment with immune-modulating therapy, which can increase their risk of infections.
 

How could COVID cause psoriasis to flare? 

Psoriasis is an autoimmune condition, and inflammation can cause symptoms.

Investigators for a study from Albany (N.Y.) Medical College and Weirton (Pa.) Medical Center found that people in the study who were already diagnosed with the skin condition had an unexpected flare within a week to a month after testing positive for COVID. New psoriasis after a COVID infection was also found. The researchers think this could be because COVID causes inflammation in the body, which negatively affects previously well-controlled psoriasis. They also think it’s possible that COVID-related inflammation could trigger a genetic tendency to have psoriasis, which may explain why it can appear for the first time after a positive test.

“A viral infection like COVID-19 can signal the release of proinflammatory factors that can appear as rashes, such as with psoriasis.” said Robert O. Carpenter, MD, director of wellness at Texas A&M University in Bryan.
 

What are the symptoms of COVID-related psoriasis?

The signs are the same as those of any form of psoriasis.
 

For a patient with psoriasis, will COVID automatically make it worse?

Not necessarily.

“Psoriasis is a common condition, so people should be aware that new psoriasis that develops may not be related to COVID-19,” said Esther Freeman MD, PhD, director of global health dermatology at Massachusetts General Hospital in Boston.

As with every aspect of COVID, doctors and scientists are still learning about how serious and widespread a problem psoriasis after COVID-19 may be. “We have seen case reports that psoriasis can flare after COVID-19,” said Dr. Freeman, who is also an associate professor of dermatology at Harvard Medical School. “I will say, this has not been a tidal wave – more like sporadic cases here and there. So I do not think psoriasis flares are a major post-COVID finding, nor do they necessarily mean you have long COVID. That being said, we know that many different infections can cause psoriasis flares, and so, in that respect, it’s not that surprising that SARS-CoV-2, like other infections, could trigger a psoriasis flare.”

Could getting COVID more than once cause psoriasis to flare? It’s possible.

“Your body can change after having COVID-19,” said Dr. Carpenter. “We don’t know the long-term implications, but having COVID-19 repeatedly can increase the risk of long COVID, which can cause many systemic changes in your body.” 

Another important point: For patients who take biologics for treating psoriasis, getting vaccinated and boosted for COVID is an important step to take to help protect themselves.
 

Is psoriasis itself a potential symptom of COVID? 

“Yes, but we don’t know the frequency at which this may occur, and a causal relationship is difficult to establish from just case reports,” said Dr. Gelfand, who’s also medical director of the clinical studies unit in the department of dermatology at his university. “Typically, if a patient presents with a flare of psoriasis, particularly guttate, pustular, or erythrodermic forms, an infectious trigger should be considered, and testing for strep and possibly COVID-19 may be appropriate.”
 

A version of this article first appeared on Medscape.com.

New research is shedding light on how an infection with COVID-19 may reactivate, or even cause, psoriasis. 

 Psoriasis has several well-established triggers, including stress, skin injury, cold or warm air, and allergies. Illnesses like strep throat can also cause a psoriasis flare in some people – and it appears COVID may also do so. “Psoriasis flares have long been associated with bacterial and viral infections, particularly a form of psoriasis called guttate, which is characterized by tons of tiny red scaly bumps all over the body,” said Joel M. Gelfand, MD, a professor of dermatology and epidemiology at the University of Pennsylvania, Philadelphia. “Infection with COVID-19 has been associated with flares of guttate and pustular psoriasis, and even psoriasis that affects 100% of the skin ... in many published case reports.”

Israeli researchers recently found that psoriasis patients have a slightly higher risk of getting COVID,  although they are not at higher risk of hospitalization or death, which could be related to treatment with immune-modulating therapy, which can increase their risk of infections.
 

How could COVID cause psoriasis to flare? 

Psoriasis is an autoimmune condition, and inflammation can cause symptoms.

Investigators for a study from Albany (N.Y.) Medical College and Weirton (Pa.) Medical Center found that people in the study who were already diagnosed with the skin condition had an unexpected flare within a week to a month after testing positive for COVID. New psoriasis after a COVID infection was also found. The researchers think this could be because COVID causes inflammation in the body, which negatively affects previously well-controlled psoriasis. They also think it’s possible that COVID-related inflammation could trigger a genetic tendency to have psoriasis, which may explain why it can appear for the first time after a positive test.

“A viral infection like COVID-19 can signal the release of proinflammatory factors that can appear as rashes, such as with psoriasis.” said Robert O. Carpenter, MD, director of wellness at Texas A&M University in Bryan.
 

What are the symptoms of COVID-related psoriasis?

The signs are the same as those of any form of psoriasis.
 

For a patient with psoriasis, will COVID automatically make it worse?

Not necessarily.

“Psoriasis is a common condition, so people should be aware that new psoriasis that develops may not be related to COVID-19,” said Esther Freeman MD, PhD, director of global health dermatology at Massachusetts General Hospital in Boston.

As with every aspect of COVID, doctors and scientists are still learning about how serious and widespread a problem psoriasis after COVID-19 may be. “We have seen case reports that psoriasis can flare after COVID-19,” said Dr. Freeman, who is also an associate professor of dermatology at Harvard Medical School. “I will say, this has not been a tidal wave – more like sporadic cases here and there. So I do not think psoriasis flares are a major post-COVID finding, nor do they necessarily mean you have long COVID. That being said, we know that many different infections can cause psoriasis flares, and so, in that respect, it’s not that surprising that SARS-CoV-2, like other infections, could trigger a psoriasis flare.”

Could getting COVID more than once cause psoriasis to flare? It’s possible.

“Your body can change after having COVID-19,” said Dr. Carpenter. “We don’t know the long-term implications, but having COVID-19 repeatedly can increase the risk of long COVID, which can cause many systemic changes in your body.” 

Another important point: For patients who take biologics for treating psoriasis, getting vaccinated and boosted for COVID is an important step to take to help protect themselves.
 

Is psoriasis itself a potential symptom of COVID? 

“Yes, but we don’t know the frequency at which this may occur, and a causal relationship is difficult to establish from just case reports,” said Dr. Gelfand, who’s also medical director of the clinical studies unit in the department of dermatology at his university. “Typically, if a patient presents with a flare of psoriasis, particularly guttate, pustular, or erythrodermic forms, an infectious trigger should be considered, and testing for strep and possibly COVID-19 may be appropriate.”
 

A version of this article first appeared on Medscape.com.

The differences between patients who have PsA with axial involvement (AxPsA) and patients who have axial spondyloarthritis with psoriasis (AxSpA+PsO) continue to remain a strong area of interest. Regierer and colleagues recently compared 359 patients with AxPsA vs 181 patients with AxSpA+PsO. These patients were enrolled into the RABBIT-SpA prospective longitudinal cohort study. Given the lack of definition of AxPsA, two definitions were used: 1) clinical judgment by the rheumatologist and 2) imaging (x-ray or MRI) findings. Regardless of clinical or imaging definition used, compared with patients who have AxSpA+PsO those with AxPsA were significantly more often women, were older, were less often HLA-B27 positive, and had more frequent peripheral manifestations but less frequent uveitis. The two diseases thus have significant differences; these should be carefully considered while making treatment decisions.

Another major research focus is on the influence of sex on PsA treatment response. Eder and colleagues conducted a post hoc analysis of pooled data from phase 3 randomized controlled trials that included 816 patients with PsA who received tofacitinib, adalimumab, or placebo. They demonstrate that at 3 months, tofacitinib was more efficacious than placebo, irrespective of sex. However, a higher proportion of men vs women receiving tofacitinib achieved minimal disease activity. This might be due to baseline differences in disease activity. The American College of Rheumatology 20/50/70 response rates were comparable. The incidence of treatment-emergent adverse events was similar in men and women receiving tofacitinib. Thus, sex significantly influences achieving low disease state. Understanding the mechanisms underlying sex differences will help improve treatment response rates in women with PsA.

Atherosclerotic vascular disease (ASVD) is an important comorbidity of PsA. Predicting ASVD remains difficult. The triglyceride-glucose (TyG) index — calculated as ln[fasting triglycerides (in mg/dL) × fasting glucose (in mg/dL)/2] — was recently identified as a marker of insulin resistance and ASVD. Xie and colleagues conducted a cross-sectional study in 165 patients with PsA who underwent carotid ultrasound and had data available for the TyG index. In a model that was adjusted for age, sex, comorbidities, smoking, BMI, low-density lipoprotein cholesterol, psoriasis area and severity index, and disease activity index for PsA, the TyG index was significantly associated with the presence of carotid atherosclerosis (adjusted odds ratio [aOR] 2.69; 95% CI 1.02-7.11) as well as carotid artery plaque (aOR 3.61; 95% CI 1.15-11.38). Thus, this easily calculated marker is associated with ASVD independent of demographic, traditional risk factors, and disease activity and needs further evaluation in prospective studies.

The differences between patients who have PsA with axial involvement (AxPsA) and patients who have axial spondyloarthritis with psoriasis (AxSpA+PsO) continue to remain a strong area of interest. Regierer and colleagues recently compared 359 patients with AxPsA vs 181 patients with AxSpA+PsO. These patients were enrolled into the RABBIT-SpA prospective longitudinal cohort study. Given the lack of definition of AxPsA, two definitions were used: 1) clinical judgment by the rheumatologist and 2) imaging (x-ray or MRI) findings. Regardless of clinical or imaging definition used, compared with patients who have AxSpA+PsO those with AxPsA were significantly more often women, were older, were less often HLA-B27 positive, and had more frequent peripheral manifestations but less frequent uveitis. The two diseases thus have significant differences; these should be carefully considered while making treatment decisions.

Another major research focus is on the influence of sex on PsA treatment response. Eder and colleagues conducted a post hoc analysis of pooled data from phase 3 randomized controlled trials that included 816 patients with PsA who received tofacitinib, adalimumab, or placebo. They demonstrate that at 3 months, tofacitinib was more efficacious than placebo, irrespective of sex. However, a higher proportion of men vs women receiving tofacitinib achieved minimal disease activity. This might be due to baseline differences in disease activity. The American College of Rheumatology 20/50/70 response rates were comparable. The incidence of treatment-emergent adverse events was similar in men and women receiving tofacitinib. Thus, sex significantly influences achieving low disease state. Understanding the mechanisms underlying sex differences will help improve treatment response rates in women with PsA.

Atherosclerotic vascular disease (ASVD) is an important comorbidity of PsA. Predicting ASVD remains difficult. The triglyceride-glucose (TyG) index — calculated as ln[fasting triglycerides (in mg/dL) × fasting glucose (in mg/dL)/2] — was recently identified as a marker of insulin resistance and ASVD. Xie and colleagues conducted a cross-sectional study in 165 patients with PsA who underwent carotid ultrasound and had data available for the TyG index. In a model that was adjusted for age, sex, comorbidities, smoking, BMI, low-density lipoprotein cholesterol, psoriasis area and severity index, and disease activity index for PsA, the TyG index was significantly associated with the presence of carotid atherosclerosis (adjusted odds ratio [aOR] 2.69; 95% CI 1.02-7.11) as well as carotid artery plaque (aOR 3.61; 95% CI 1.15-11.38). Thus, this easily calculated marker is associated with ASVD independent of demographic, traditional risk factors, and disease activity and needs further evaluation in prospective studies.

The differences between patients who have PsA with axial involvement (AxPsA) and patients who have axial spondyloarthritis with psoriasis (AxSpA+PsO) continue to remain a strong area of interest. Regierer and colleagues recently compared 359 patients with AxPsA vs 181 patients with AxSpA+PsO. These patients were enrolled into the RABBIT-SpA prospective longitudinal cohort study. Given the lack of definition of AxPsA, two definitions were used: 1) clinical judgment by the rheumatologist and 2) imaging (x-ray or MRI) findings. Regardless of clinical or imaging definition used, compared with patients who have AxSpA+PsO those with AxPsA were significantly more often women, were older, were less often HLA-B27 positive, and had more frequent peripheral manifestations but less frequent uveitis. The two diseases thus have significant differences; these should be carefully considered while making treatment decisions.

Another major research focus is on the influence of sex on PsA treatment response. Eder and colleagues conducted a post hoc analysis of pooled data from phase 3 randomized controlled trials that included 816 patients with PsA who received tofacitinib, adalimumab, or placebo. They demonstrate that at 3 months, tofacitinib was more efficacious than placebo, irrespective of sex. However, a higher proportion of men vs women receiving tofacitinib achieved minimal disease activity. This might be due to baseline differences in disease activity. The American College of Rheumatology 20/50/70 response rates were comparable. The incidence of treatment-emergent adverse events was similar in men and women receiving tofacitinib. Thus, sex significantly influences achieving low disease state. Understanding the mechanisms underlying sex differences will help improve treatment response rates in women with PsA.

Atherosclerotic vascular disease (ASVD) is an important comorbidity of PsA. Predicting ASVD remains difficult. The triglyceride-glucose (TyG) index — calculated as ln[fasting triglycerides (in mg/dL) × fasting glucose (in mg/dL)/2] — was recently identified as a marker of insulin resistance and ASVD. Xie and colleagues conducted a cross-sectional study in 165 patients with PsA who underwent carotid ultrasound and had data available for the TyG index. In a model that was adjusted for age, sex, comorbidities, smoking, BMI, low-density lipoprotein cholesterol, psoriasis area and severity index, and disease activity index for PsA, the TyG index was significantly associated with the presence of carotid atherosclerosis (adjusted odds ratio [aOR] 2.69; 95% CI 1.02-7.11) as well as carotid artery plaque (aOR 3.61; 95% CI 1.15-11.38). Thus, this easily calculated marker is associated with ASVD independent of demographic, traditional risk factors, and disease activity and needs further evaluation in prospective studies.