Methotrexate monotherapy versus methotrexate and apremilast combination therapy in the treatment of palmoplantar psoriasis: A prospective, randomised, assessor-blinded, comparative study

Abstract

Background Palmoplantar psoriasis is a chronic debilitating condition which significantly impairs quality of life. Objectives To assess the efficacy and safety of the combination of apremilast and methotrexate compared with methotrexate monotherapy in the treatment of palmoplantar psoriasis. Also, to study the impact on treatment on the Dermatology Life Quality Index and Palmoplantar Quality of Life Index. Methods A total of 64 patients were randomised to two groups in a 1:1 ratio - Group A received both methotrexate and apremilast in combination, while Group B received only methotrexate, for 16 weeks. The primary endpoints were the mean score of Modified Palmoplantar Psoriasis Area and Severity Index at week 16, the proportion of patients achieving modified palmoplantar psoriasis area severity index-75 and/or Palmoplantar Psoriasis Physician Global Assessment score 0/1 at week 16. Results A significantly higher proportion of patients in Group A achieved Modified Palmoplantar Psoriasis Area and Severity Index-75 at week 16 (43% in Group A vs 30% in Group B). The Modified Palmoplantar Psoriasis Area and Severity Index score was significantly lower in the combination group at week 16 (4.03 ± 2.05 in Group A and 5.89 ± 2.31 in Group B, P-value = 0.002). About 80% of patients in the combination group with baseline Palmoplantar Psoriasis Physician Global Assessment ≥3 achieved Palmoplantar Psoriasis Physician Global Assessment 0/1 compared to 60% in Group B. The combination group showed a significantly higher reduction in Dermatology Life Quality Index and Palmoplantar Quality of Life Index scores compared to the methotrexate alone group (P-value = 0.025). No notable adverse events were observed. Limitation The limitations of the study were single blinding, small sample size and a lack of longer follow up to assess the rate of relapse. We did not account for attrition during sample size calculation. Also, due to the paucity of data regarding the use of apremilast in palmoplantar psoriasis, definitive comparisons could not be made with previous studies. Conclusion The combination of apremilast and methotrexate has superior efficacy and a similar safety profile as compared to methotrexate monotherapy for the treatment of moderate to severe palmoplantar psoriasis.

Apremilast in Palmoplantar Psoriasis and Palmoplantar Pustulosis: A Systematic Review and Meta-analysis

“…1 ). These 17 publications consisted of five placebo-controlled RCTs [ 11 , 12 , 14 – 17 ], one single-arm phase II clinical trial [ 18 ], two randomized methotrexate comparative trials [ 19 , 20 ], six prospective/retrospective cohort studies [ 21 – 26 ], and three case series [ 27 – 29 ], totaling 1117 subjects with palmoplantar disease treated with apremilast or placebo. Of the 1117 subjects with palmoplantar disease, 948 cases of PP and 169 cases of PPP were represented.…”

“…A total of 12 publications investigated patients with PP treated with apremilast (APR) including four placebo (PBO)-controlled RCTs [ 11 , 12 , 14 – 16 ], two randomized methotrexate (MTX) comparative trials [ 19 , 20 ], four prospective/retrospective cohort studies [ 22 – 24 , 26 ], and two case series [ 27 , 29 ] (Table 1 ).…”

“…[ 19 ] 2021 MTX comparative trial Apremilast vs. methotrexate 84 (76/84 PP, 8/84 PPP) 59.5 vs. 64.3 (APR vs. MTX) (week 16) Median PPPASI improvement (%): 62.3 vs. 65.8 (APR vs. MTX) (week 16) [ P = 0.39, (95% CI = – 4.2–2.1)] PPPASI 75 (%): 33.3 vs. 40.5 (APR vs. MTX) (week 16) [ P = 0.49] Mean DLQI improvement (%): 50.0 vs. 47.6 (APR vs. MTX) (week 16) [ P = 0.99 (95% CI = – 1.0–2.0)] Hassanandani et al . 2022 [ 20 ] MTX comparative trial Apremilast methotrexate combination vs. methotrexate 60 (baseline PPPGA ≥ 3) 80.0 vs. 60.0 (APR + MTX vs. MTX) (week 16) [ P = < 0.05] Mean PPPASI improvement (%): 81.5 vs. 71.7 (APR + MTX vs. MTX) (week 16) [ P = 0.002] PPPASI 75 (%): 43.3 vs. 30.0 (APR + MTX vs. MTX) (week 16) [ P = 0.001] Mean DLQI improvement (%): 66.9 vs. 58.9 (APR + MTX vs. MTX) (week 16) [ P = 0.001] Ioannides et al . 2021 [ 22 ] APRAISAL Prospective Cohort None 111 (44 with baseline PPPGA ≥ 3) 72.7 (week 52) [95% CI = 59.6–85.9] Median DLQI score improvement (%): 75.0 (week 24) (includes non-palmoplantar psoriasis) Del Alcázar et al .…”

“…In a randomized comparative trial by Hassanandani et al . [ 20 ], apremilast in combination with methotrexate was shown to be more effective versus methotrexate monotherapy in achieving PPPGA of 0 or 1 at week 16 in patients with moderate to severe PP (baseline PPPGA ≥ 3) (80.0 vs. 60.0%) ( n = 60) [ P = < 0.05].…”

A Comparative Study of the Efficacy of Methotrexate versus Methotrexate with Apremilast in Moderate to Severe Chronic Plaque Psoriasis

“…In a recent randomised comparative trial conducted by Hassanandani et al .,[ 20 ] the combination therapy of Methotrexate with Apremilast was found to be more effective than methotrexate monotherapy in achieving a Palmoplantar Physician Global Assessment (PPPGA) score of 0 or 1 at week 16 in patients with palmoplantar psoriasis (baseline PPPGA ≥ 3). The study enrolled a total of 60 patients, and the results indicated that the combination therapy was significantly more effective than the monotherapy in achieving the desired outcome (80.0% vs. 60.0%, respectively; P < 0.05).…”