JAK Inhibitors Outperform Anti-TNFs in Relieving Rheumatoid Arthritis Pain

A retrospective study in Sweden found that targeted drugs for rheumatoid arthritis (RA) were not equal in pain relief, but the differences appeared modest.

Three months after starting a new targeted RA treatment, patients taking Janus kinase (JAK) inhibitors reported a pain reduction of an average of 4.0 points (95% CI 1.6–6.3) on a 100-point scale compared with those taking tumor necrosis factor (TNF) inhibitors, according to Dr. Anna Eberhard of Lund University in Malmö, Sweden, and colleagues. The difference reflected adjustments for patient demographics, disease characteristics, and prior and current treatments.

The researchers noted that “similar trends” that fell short of statistical significance were also seen when comparing JAK inhibitors to less popular types of biologic treatments, such as interleukin (IL)-6 inhibitors, the T-cell inhibitor abatacept (Orencia) and the B-cell depleting agent rituximab (Rituxan). It was reported Arthritis and Rheumatology.

Eberhard and colleagues observed that the advantage of JAK inhibitors was particularly evident when these agents were used alone and in patients who had previously tried other types of therapy. However, for patients starting their first targeted therapy, IL-6 inhibitors such as tocilizumab (Actemra) stood out, with 3-month pain scores falling 10 to 12 points more than those seen with JAK inhibitors, anti-TNFs, or rituximab.

Eberhard’s group also looked at pain scores 12 months after starting treatment, but these data were not collected for more than half of the patients initially included. For those who had been on treatment for that long, the odds of achieving “low pain” (less than 20 out of 100) were numerically higher with JAK inhibitors than with anti-TNF inhibitors or anti-IL-6 drugs. But the differences of 3.3 to 3.5 points were not statistically significant. The odds of low pain in patients taking abatacept and rituximab were about the same as in patients taking JAK inhibitors.

Pain is the most important patient-centered aspect of RA, and although clinical assessment tools such as the Clinical Disease Activity Index (CDAI) include measures of pain, they are not specifically emphasized. Drug efficacy studies often use these composite measures as primary endpoints, while pain itself is usually a secondary outcome if reported. Eberhard and colleagues noted that “only limited results have been obtained from observational studies comparing the effectiveness of biologic RA drugs and JAK inhibitors in relieving pain.”

The current study used the Swedish Rheumatology Quality Register, which includes about 95% of all Swedes with RA treated with advanced therapies. Eberhard and colleagues analyzed a total of 8,430 people, members of the register who started one of five classes of medication between 2017 and 2019. In addition to pain ratings, the data included dates of treatment start and end, concomitant treatments such as methotrexate and steroids, and measures of disease severity and clinical response. Other national registries provided data on comorbidities, hospitalizations, and other parameters used in the researchers’ statistical adjustments.

More than 75% of the cohort started a TNF inhibitor during the selected time period. For the remainder, JAK inhibitors were most common (1,827 patients; 82% baricitinib (Olumiant)), followed by rituximab (n=1,149), abatacept (n=1,102), and anti-IL-6 drugs (n=887, 80% tocilizumab). Median patient age was approximately 60 years, and approximately 80% were female.

Average pain ratings at baseline ranged from 56 to 65 across the five treatment types. After 3 months of treatment, the average reduction was in the 17 to 20 point range, but the gross differences between the drug types were hardly similar to those seen after statistical adjustments — a necessary step to account for factors influencing treatment choices.

Most patients were able to continue treatment once they started, and they had retention rates of about 60% to 80% through 12 months (rituximab had the highest retention rate and IL-6 inhibitors the lowest). In addition, pain relief appeared to be associated with overall effectiveness. Standard assessments showed that about half of the patients who were in “low pain” clinical remission at 12 months and another third had low disease activity—an overall response rate of 80% to 85% for the five types of drugs.

The most important limitation of the study was that collection of important data was often patchy. Baseline pain scores were missing for about a third of patients, and more than half had insufficient pain data at 3 and 12 months. Furthermore, not every potentially relevant factor was captured in the records, leaving room for unmeasured confounding. Furthermore, treatment patterns in Sweden were likely different from other countries, including the United States, which could limit the generalizability of the study.