Tofacitinib an effective painkiller in rheumatic musculoskeletal diseases

The oral Janus kinase inhibitor tofacitinib provides rapid and sustained pain relief across several inflammatory rheumatic musculoskeletal diseases, namely rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS), according to a posthoc analysis of randomized controlled trials.

Pain reduction in patients treated with tofacitinib may be attributed to its effect on inflammation, with the drug shown to effectively reduce spinal inflammation in AS and downregulate proinflammatory pathways in both RA and PsA models, the investigators said. [Ann Rheum Dis 2017;76:1340-1347; Arthritis Rheum 2012;64:3856-3866; Ann Rheum Dis 2016;75:311-315]

Using unidimensional pain measures and pain-specific components within multidimensional assessments, the investigators evaluated the efficacy of tofacitinib at easing pain in one phase II (AS) and six phase III (four RA, two PsA) studies. The total population comprised 3,330 patients. Patients in the RA cohort were generally older than those in the PsA and AS cohorts, with a longer average time since diagnosis. Most of the RA patients were female, while AS patients were mostly male.

Analysis was stratified according to rheumatic disease diagnosis and category of prior inadequate response (IR) to treatment: conventional synthetic disease-modifying antirheumatic drug (csDMARD)-IR (RA and PsA), tumour necrosis factor inhibitor (TNFI)-IR (RA and PsA), and nonsteroidal anti-inflammatory drugs (NSAID)-IR (AS).

Overall, treatment with tofacitinib 5 mg or 10 mg twice daily yielded improvements in all pain assessments across all cohorts as compared with placebo. Pain relief in RA and PsA csDMARD-IR and TNFi-IR populations occurred as early as week 2 and persisted at month 3 (p<0.001). Improvements were broadly sustained through month 6. [RMD Open 2020;6:e001042]

Meanwhile, in the AS NSAID-IR population, pain relief was observed at week 12.

Pain was assessed using the following measures: Patient’s Assessment of Arthritis Pain, Short-Form Health Survey 36v2 Question (Q)7 and Bodily Pain domain, Ankylosing Spondylitis Quality of Life Q9 and Q14, EuroQol Five Dimensions Pain/Discomfort dimension, and Bath Ankylosing Spondylitis Disease Activity Index Q2 and Q3.

“The experience of pain may be different between patients with RA, PsA or AS due to the distinctive phenotypes and clinical pattern of presentation. For example, in PsA, the presence and severity of both skin and joint disease may change patients’ interpretation of pain relative to the potentially more joint-specific pain experienced by patients with RA,” the investigators pointed out.

Despite the potential differences in pain experience, tofacitinib helped eased pain across different aspects of pain, regardless of dose and previous treatment, they added. This is in line with the results of previous studies on bDMARD interventions in RA, PsA or AS, which reported that TNFi therapy improved patient-reported pain. [Health Qual Life Outcomes 2014;12:102; Ann Rheum Dis 2007;66:163-168; Arthritis Care Res 2014;66:1085-1092; J Rheumatol 2010;37:1221-1227; Cochrane Database Systemic Reviews 2015;4:CD005468]

“Further studies are needed to understand the mechanisms of pain in rheumatic diseases, how they differ between these diseases and how best to treat pain,” the investigators said.