The effect of tofacitinib on residual pain in patients with rheumatoid arthritis and psoriatic arthritis

Abstract

Objective: Post hoc analysis of pooled data from nine randomised controlled trials to assess the effect of tofacitinib (oral Janus kinase inhibitor for treatment of rheumatoid arthritis (RA) and psoriatic arthritis (PsA)) on residual pain in patients with RA or PsA with abrogated inflammation.

Methods: Patients who received ≥1 dose of tofacitinib 5 mg twice daily, adalimumab or placebo with/without background conventional synthetic disease-modifying antirheumatic drugs and had abrogated inflammation (swollen joint count (SJC)=0 and C reactive protein (CRP)<6 mg/L) after 3 months' therapy were included. Assessments included Patient's Assessment of Arthritis Pain at month 3 (Visual Analogue Scale [VAS] 0-100 mm). Scores were summarised descriptively; treatment comparisons assessed by Bayesian network meta-analyses (BNMA).

Results: From the total population with RA/PsA, 14.9% (382 of 2568), 17.1% (118 of 691) and 5.5% (50 of 909) of patients receiving tofacitinib, adalimumab and placebo, respectively, had abrogated inflammation after 3 months' therapy. Patients with RA/PsA with abrogated inflammation receiving tofacitinib/adalimumab had higher baseline CRP versus placebo; patients with RA receiving tofacitinib/adalimumab had lower SJC and longer disease duration versus placebo. Median residual pain (VAS) at month 3 was 17.0, 19.0 and 33.5 in patients with RA treated with tofacitinib, adalimumab or placebo, and 24.0, 21.0 and 27.0 in patients with PsA, respectively. Residual pain reductions with tofacitinib/adalimumab versus placebo were less prominent in patients with PsA versus patients with RA, with no significant differences between tofacitinib/adalimumab, per BNMA.

Conclusion: Patients with RA/PsA with abrogated inflammation receiving tofacitinib/adalimumab had greater residual pain reduction versus placebo at month 3. Results were similar between tofacitinib and adalimumab.

Trial registration number: ClinicalTrials.gov registry (NCT00960440; NCT00847613; NCT00814307; NCT00856544; NCT00853385; NCT01039688; NCT02187055; NCT01877668; NCT01882439).

Keywords: Arthritis, Psoriatic; Arthritis, Rheumatoid; Inflammation.

Figure 1

Proportion of patients with an abrogation of inflammation^a after 3 months of therapy by indication. ^aAn abrogation of inflammation was defined as SJC=0 and CRP <6 mg/L. BID, twice daily; CRP, C-reactive protein; N, number of patients evaluated; n, number of patients with an abrogation of inflammation after 3 months of therapy; PsA, psoriatic arthritis; RA, rheumatoid arthritis; SJC, swollen joint count.

Figure 2

Patient’s Assessment of Arthritis Pain in patients with an abrogation of inflammation^a after 3 months of therapy: (A) pain (VAS) scores and (B) Bayesian network meta-analysis. ^aAn abrogation of inflammation defined as SJC=0 and CRP <6 mg/L. ^bProb(d<0): posterior probability of a larger pain reduction. ^cAnalysis adjusted for age, sex, disease duration, month 0 pain, month 3 corticosteroid treatment, month 3 analgesic treatment and month 3 methotrexate treatment. ^dAnalysis adjusted for age, sex, disease duration, month 0 PASI, month 0 pain, month 3 corticosteroid treatment, month 3 analgesic treatment and month 3 methotrexate treatment. ^eAnalysis adjusted for disease, age, sex, disease duration, month 0 PASI, month 0 pain, month 3 corticosteroid treatment, month 3 analgesic treatment and month 3 methotrexate treatment. BID, twice daily; CrI, credible interval; CRP, C-reactive protein; d, difference; N, number of patients evaluated; PASI, Psoriasis Area Severity Index; Prob, probability; PsA, psoriatic arthritis; Q1, first quartile (25th percentile); Q3, third quartile (75th percentile); RA, rheumatoid arthritis; SJC, swollen joint count; VAS, Visual Analogue Scale.

Figure 3

(A) Proportion of patients with a 50% decrease in Patient’s Assessment of Arthritis Pain at month 3 compared with baseline with (B) Bayesian network meta-analysis; (C) Proportion of patients with Patient’s Assessment of Arthritis Pain score <20 with (D) Bayesian network meta-analysis; and (E) Proportion of patients with Patient’s Assessment of Arthritis Pain score <30 with (F) Bayesian network analysis in patients with an abrogation of inflammation^a after 3 months of therapy. ^aAn abrogation of inflammation was defined as SJC=0 and CRP <6 mg/L. ^bProb(d>0): posterior probability of a larger proportion of patients with a pain improvement. ^cAnalysis adjusted for age, sex, disease duration, month 0 pain, month 3 corticosteroid treatment, month 3 analgesic treatment and month 3 methotrexate treatment. ^dAnalysis adjusted for age, sex, disease duration, month 0 PASI, month 0 pain, month 3 corticosteroid treatment, month 3 analgesic treatment and month 3 methotrexate treatment. ^eAnalysis adjusted for disease, age, sex, disease duration, month 0 PASI, month 0 pain, month 3 corticosteroid treatment, month 3 analgesic treatment and month 3 methotrexate treatment. BID, twice daily; CrI, credible interval; CRP, C-reactive protein; d, difference; N, number of patients evaluated; n, number of patients achieving respective outcome; PASI, Psoriasis Area Severity Index; Prob, probability; PsA, psoriatic arthritis; RA, rheumatoid arthritis; SJC, swollen joint count.